Arnica / Arnica Montana

General features: It is herbaceous aromatic perennial non-edible flowering plant belonging to Asteraceae family (sunflower family) holding large flower head. The name originates from the Greek word ‘arni’ meaning lamb due to its soft and hairy leaves. However, it is also colloquially named as Mountain tobacco or Leopard’s bane or Wolfsbane. Although these names are also used for a different herb eg, Aconitum which is highly poisonous by nature. Arnica has nearly forty different species. The plant grows in sub-alpine temperate zones of North America and northern Eurasia at about ~ 10,000 ft high altitude. The major usable species is Arnica Montana (AM), which is widely famed as pain medication. For extensive period of time, it has been used as herbal medicine owing to its anti-inflammatory and analgesic effects. The species, AM is abundant in many European nations like England and several of Balkan states or some parts of northern Italy. It is noticed to be in large use within East European countries particularly within Balkan nations. AM grows in nutrient poor silica rich soils. In a strange way this species is steadily declining from the earth. In recent days, the demand is very high. It is now considered as an endangered species in most of the European nations. According to USDA, AM is regarded as hazardous herb due to the toxic nature for possessing Helenalin, a poisonous sesquiterpene. If orally consumed the plant produces gastroenteritis or bleeding of the digestive tract or even damaging the liver. It enhances the heart rate, exerts muscular weaknesses, and produces nervousness even causing skin irritation. It is also proven to be mutagenic. If ingested at high doses it may bring fatality.

As per the description, plant sizes vary widely between 8 – 24 inches in height. The plant or its bright yellow colored flowers spread pleasant aroma. The flowering season starts between May to August in Europe. The basal leaves are dark green and ovate with rounded tips which are bright colored. The upper leaves are spear shaped and opposed, exception within Asteraceae family. The bright yellow flowers are built by yellow disc florets at the center and orange – yellow florets at the outside part. Uniquely, the plant can survive in extreme weather condition. AM grows rhizomes that grows in two years cycle.

Folk / traditional medicinal uses:  Historically, AM is in use over the centuries as herbal medicine. Often hydro-alcoholic extract or ointment or gel prepared from leaves and roots are externally used for potent anti-inflammatory, anti-neuralgic, bactericidal, anti-rheumatic, anti-septic, and counter-irritant and wound healing effects. As per its analgesic and antiinflammatory efficiency, it is quite similar to Willow bark or even Ibuprofen. It is mostly used externally due to the toxicity so often applied topically to treat bruises, boils, edema, contusions, hematoma, joint pain, sprains, muscle pain, thrombosis, alopecia neurotic, rheumatic arthritis and osteoarthritis. Rubbing arnica oil on the scalp increases hair growth. In the past, AM is occasionally taken at a low dose internally for its cardiotonic, CNS stimulant, expectorant, and sedative and nervine action. It is infrequently used to treat liver, stomach and intestinal cancers. Arnica at very high dilution is often administered as homeopathic medicine (mother tincture = 1-10 dilution).

Chemical components: More than 150 physiologically active phyto-compounds have been identified within Arnica Montana plant consisting of sesquiterpene lactones like Helenalin, 11a, 13-dihydro-helenanlin and its short chain acid esters (0.3 to 1.0 % dry wt in flower head and 0.1 to 0.5 % in leaf), flavonoids (0.6 to 1.7 %) in the form of glycosides, glucuronides or aglycones; essential oil (long chain fatty acids), thymol derivatives, mono and sesquiterpenes. The other constituents are carotenoids, diterpenes, Amidiol (triterpene), pyrrolizidine alkaloids (Tussilagine and Iso-tussilagidine), polacetylenes, coumarins (Umbelliferone and Scopoletin), Phenolic acids (Chlorogenic acid, Caffeic acid and cynarin, 1.0 – 2.2 %), Liganans, dicafeoyl quinic acid derivatives and oligosaccharides. It produces sesquiterpene lactones of various derivatives of Helenalin (dihydro Helenalin, 2, 3 dihydro-aromaticin and others), Trans-Caryophyllene, Germacrene, β – farnesene, Mexicanin, Chemissonoid etc. The major flavonoids are Apigenin, Luteolin, Hispidulin, Quercitin and Kaempferol and its glycoside derivatives. The constituents of AM are categorized below.

Flower – The flower contains large quantity of flavonoids (0.4 – 0.6%), sesquiterpenes, acetylenes, hydroxy-coumarin, phenyl acrylic acid and moderate level of essential oil (0.2 – 0.35%), phenyl carbonic acid (chlorogenic acid, Caffeic acid, Cynarin), pyrrolizidine alkaloids (Tussilagin and Isotussilagin).

 

The flowers also synthesize sesquiterpene lactones like Helenalin and its associated derivatives including 11a, 13-dihydro-helenalin and 2, 3 dihydro-aromaticin, Mexicanin and Chemissonoid. In addition it synthesizes coumarin derivatives like Umbelliferone and Scopoletin. The level of sesquiterpene lactone varies with the maturity of flowers. Usually, sesquiterpene lactones are known for its potent anti-inflammatory and cytotoxic role in physiology. Normally, most pyrrolizidine alkaloids are known to be hepato-toxic but experiments indicate that Tussilagine or Iso-tussilagine does not possess that property. Contrarily, they exert beneficial immune-modulatory actions helping prevent cancers even multiple myeloma. Umbelliferone and Scopoletin are phyto-coumarins. They undergo synthesis inside the plants following Phenylpropanoid pathway using L-phenylalanine. Coumarin derivatives show various physiologic actions acting as anticoagulant, antibacterial, antiinflammatory, antitumor, and anti-hyperglycemic and molluscidal agent.

Seeds – It contains mostly phenolic acids (Chlorogenic acid and Caffeic acid) and flavonoids (Quercitin and kaempferol, Luteolin and Apigenin) and its glycosides. All of them have strong anti-oxidant role thus subsequently exert anti-inflammatory as well as anti-neoplastic effect. They also impose anti-atherosclerotic function therefore good for the cardiac health. It also possesses sesquiterpene lactones which are seen to be potent biochemically for anti-inflammatory role.

Roots – The major components of rhizome and root are essential oil containing approximately 56 bioactive ingredients. Some of them are shown below.

Major constituents of essential oil from Arnica Montana root

Pharmacological effects: From very ancient time Arnica Montana has been widely used either for healing or cosmetic purposes or for using in the liquer. Plenty of pharmaceuticals are identified also constructed based on the chemical structure and properties of its ingredients from leaves or roots of the plant. The most active constituents are sesquiterpene lactones which have proven significant ability to reduce inflammation and subsequently reducing the pain due to the excellent immunomodulatory role. It also acts as tonic to the nervous system. The extract of Arnica has strong anti-oxidant property also exerts cytotoxic effect. It helps stimulate the circulation enabling to raise the blood pressure within coronary arteries. The most common uses of AM are aimed to provide relief for arthritis, ulcers, burns, eczema and acne. Besides powerful antibacterial actions, it can also reduce pain and inflammation considerably. It is noteworthy that majority of the use is only applicable externally. Usually, the oral administration of any parts of AM extract is not recommended.

Anti-inflammatory effect – Most sesquiterpene lactones show considerable anti-inflammatory actions. Among those Helenalin stands out to be the most potent one. The molecule inhibits the activation of nuclear transcription factor NF – κβ which is the actual mediator of immune response. Its antiinflammatory action is quite different from non-steroidal antiinflammatory (NSAID), indomethacin or aspirin. The molecule directly and selectively alkylates p65 subunit of NF – κβ using its lactone moiety thereby preventing the activation and subsequent inflammatory action. The extract of AM also prevent degranulation of mast cells and histamine release. In that way, it increases the vascular permeability. Thus considering the overall act it can act as anti-allergic also.

Anti-osteoarthritic property – Experiments conducted by preparing a gel from Arnica Montana extract or separately using Helenalin or 11α, 13-di-hydro Helenalin or its ester offers significant anti-osteoarthritic effect. Studies further show that complete inhibition of NF – κβ by the Helenalin and its other derivatives are quite identical to glucocorticoids on inflammatory cascade even in the case of permeation through skin. The action is also very same as ibuprofen.

Analgesic effect – Experiments indicate that the presence of high level Thymol, a monoterpenoid phenol in AM extract is presumably one of the major underlying causes behind the analgesic as well as anti-inflammatory effects which might occur by inhibiting the recruitment of cytokines and chemokines. The overall actions also rest on antioxidant role by scavenging the free radicals and other subsequent related events. Further, Thymol inhibits T cell immune response while improving the action of T-helper cells (Th1) (IL-2) and IFN – γ / Th-2 (IL-4), IL-5 and IL-10 involved in the anti-inflammatory activities. Thymol also downregulates mitogen activated protein kinase and NF – κβ signaling pathways.

Anti-oxidant effect – The extracts indicate produce considerable anti-oxidant effect which is due to the presence of flavonoids and phenolic compounds. Arnica shows considerable reduction of mitochondrial O₂ consumption. It also provides protection from Ca⁺² and inorganic PO₄ induced hepatic mitochondrial membrane permeability, lipid peroxidation produced by Fe⁺² – citrate and ROS mediated protein fragmentation.

Inotropic effect – Experiments reveal that Helenalin and its derivatives impose positive inotropic effect on myocardium isolated from guniepig within the range of 10^-5 to 10^-3 M / L concentrations. Essentially, it increases the release of Ca⁺² from the sarcoplasmic reticulum thus enhancing the influx within the cytosol of heart muscle cells. Studies further show that at higher concentrations above 10^-3 M / L the compound(s) creates irreversible negative inotropic effect, lowering the level of cytosolic Ca⁺² thereby weakening the force of heart muscle contraction.

Anxiolytic effect – Numerous physiologic experiments identify the anxiolytic action of AM plant extract which is not due to the presence of flavonoids or tannins. The exact compound(s) is not identified but the effect is comparable to the commercially available drugs Diazepam (Valium) by enhancing the action of GABA.

Anti-platelet action – The crude extract of AM leaves, stems or roots exert anti-platelet aggregating action. The identifiable compounds are sesquiterpene lactones, Helenalin and 11α, 13 – dihydro-Helenalin which enable to prevent collagen induced platelet aggregation, thromboxane formation including also serotonin secretion. The actions can be blocked by thiol containing compounds or cysteine. This along with the other experiments indicate that sesquiterpene lactones react with the – SH group(s) on platelet surface facilitating to prevent the aggregation. The event could be related to reduction of Phospholipase – A₂ action thus inhibiting the Arachidonic acid metabolism pathway subsequently barring the production of Thromboxane also.

Anti-hair loss activity – It has been known for a long time that the essential oil of AM can boost hair growth. The major identifiable compounds are essential oil, fatty acids, thymol, sesquiterpene lactones of pseudo-guaianolides and flavanone glycosides. The active component among those items is possibly thymol. Among the numerous physiological role, thymol has ability to enhance the circulation thereby allowing the micronutrients enriching the needs of hair follicles.

Microbial and insecticidal effect – Experiments conducted by agar diffusion method have proven that extract of Arnica exhibit potent anti-microbial, insecticidal and fungicidal property. The presence of Thymol and few of its derivatives are recognized to be one of the causes. The presence of Helenalin and its related derivatives are thought to be the underlying cause.

Uterotonic effect – The alcoholic extract of flower heads show potent uterotonic action by contracting the uterine muscle of rabbits, cats and rats when injected intravenously. The effect is considered to be due to the presence of sesquiterpene lactones in the plant.

Effect of respiration – The extract of AM can increase respiratory frequency 35 – 45 % in rats, rabbits if injected intravenously. The identifiable component is 6 – O- acetyl-11, 13-dihydro-helenalin.

Hypopigmentation effect – The extract of AM or its purified product consists of several sesquiterpene lactones, particularly Helenalin 2 – methyl butyrate induces Heat shock protein – 70 (Hsp70) gene expression including the transcription factor – 1 of Hsp 70 with incremental doses. The protein Hsp70 uniquely helps hypopigmentation by lowering the melanin production as well as the activity of Tyrosinase. In that way either purified derivative Helenalin 2-methyl butyrate or AM extract is often added to the cosmetics for creating fair skin by lowering melanin formation.

Immunomodulatory effect – Several polysaccharides from AM flowers have significant immune-stimulating property enhancing the phagocytosis of granulocytes. For example, arabino-3, 6-galactan protein of Mw 10⁵ KD enable to activate macrophages releasing TNF that increases phagocytosis. Some other fractions isolated also follow the similar role.

Toxicology: According to Food and Drug Administration (FDA) of United States, Arnica Montana is toxic and unsafe for oral consumption, so it has been advised not to apply on cuts or at any bleeding events. The plant has large reserve of Helenalin and its derivatives are considered toxic thus not to consume orally which might produce gastrointestinal problems including bleeding inside the gastric tract or damaging the liver. In many occasions it often produces nervousness, muscular weakness and acceleration of heart rate. It is also suspected to be mutagenic.

 

 

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Tylophora Indica / Indian Ipecac / Antmool / অন্তমূল।

General features: The plant, Tylophora Indica (TI) is a native of India, particularly growing in Uttar Pradesh, West Bengal, Assam, Orissa, Himachal Pradesh also in some areas of north eastern Sub- Himalyan regions. Besides India, it grows in other South Asian nations of tropical and subtropical regions and in many places of African continent. The name Tylophora originates from the word “Tylos” implicating a knot whereas “phoros’ indicates bearing. It has been considered as a medicinal plant from the time of Ayurveda, having noticeable impact on common diseases like allergies, cold, particularly against asthma or bronchitis. The plant belongs to Apocyanacea (subclass, Asclepiadaceae) family. It is a slender hairy branching climber with ~ 5 ft long stems having rhizome ~ 0.12 inch thick. The leaves are ovate – oblong, 1.2 – 4 inches long and 0.6 – 3 inches wide, deep green color, differentiated in 2 – 3 layered palisade tissue and 6 – 8 spongy parenchyma layers having rosettes of Calciun Oxalate cystals. The roots are long and light brown in color also somewhat fleshy having corky bark. The plant is usually propagated via seeds but their viability is low. The flowers are small 0.4 – 0.6 inch long and 2 – 3 flowered fascicles in axillary umbellate cymes. Corollas are greenish yellow or greenish purple. The lobes are oblong acute. Fruits are follicle 2.8 x 0.4 inch, ovoid lanceolate and tapering at apex. Seeds are 0.3 long and 0.15 inch wide. The english name is Indian Ipecac. In Hindi or Bengali language, it is called Antmool / অন্তমূল।  It is a huge reservoir of plant alkaloids, 0.2 – 0.5 %. In Ayurveda its use is mentioned to treat the allergies, dermatitis and rheumatism. In recent days, it has been established that it has numerous medicinal role concerning antioxidant, antiinflammatory, antitumor hyperlipidemic, immunomodulatory, antistress, anti-plasmodium, antimcrobial, antihyperglycemic and radical scavanging activities. Studies reveal further that it also potent inhibitory effect on HIV infection. The plant extract exerts strong diuresis and additionally it can act as hepatoprotective agent. Research also indicates that in vitro raised plants enable to synthesize higher level of alkaloids in comparison to normal ones grown in the field. Due to its much importance for medicinal values TI is now produced by culturing in vitro. A number of antibacterial compounds are also biotechnologically synthesized by means of in vitro culture. Interestingly, adding Salicylic acid, Ornithine, cinnamic acid, Tyrosine and Phenylalanine ~ 10 – 20 mg / 100 ml and sucrose ~ 3 % to the suspension medium will help boost the synthesis of antioxidant components, Kaempaferol and others in the callus.

Folk medicinal uses: As a folk medicine, TI leaf extract is very useful as expectorant to reduce or cure respiratory infections, bronchitis and whooping cough. The extract also produces strong analgesic effect. The extract also finds application for releiving allergies and hay fever. In rural areas the decoction prepared by extracting root and leaf by water is used in treating Lucorrhea.

Phytoconstituents: The plant has unique capability to synthesize numerous analogs of Phenanthroindolizidine alkaloids which have immense medicinal potentials. Due to the production of physiologically active alkaloids, TI occupies distinctive position within the medicinal plant community. Besides alkaloids, the plant produces steroids, flavonoids, tannins, amino acids, starch, saponins and glycosides. Below is a list of major phyto-components produced within the plant parts.

Plant body – Alkaloids (0.2 – 0.46 %) → Septicine, Tylophorinidine, Tylophorine, Isotylocerebrine, Tylophorecine, Tylophoreinine, Tyloindicines A – E and numerous other metabolites and derivatives.

Major Phenanthroindolizidine alkaloids and its analogs in Tylophora Indica

The majority of phenanthroindolizidine alkaloids or its derivatives have strong cytotoxic effect on various cancer cells. In addition some of them have potent anti-inflammatory (84 nM – 20 µM) and analgesic role. Tylophorine, the chief ingredient of TI exerts useful antiproliferative action on human leukemia cell line (HL- 60). It also wields growth inhibitory actions on human liver carcinomas (Hep -G), human pancreatic cell line (PANC-1), human breast cancer cell line (MCF-7) and human T lymphoblastic cell line (CEM). Its cytotoxicity is also noticed toward murine macrophage oriented Abelson leukemia virus transformed cell line, RAW264.7. Tylophorine mostly works by inhibiting NF – κβ mediated transcription. Its anti-inflammatory effect is via the inhibition of TNF – α. Tylophorinine another analog is similarly effective in controlling varieties of cancer cells like Hep – G2, numerous non-small cell lung carcinomas (NCI-H23, NCI-H226, NCI – 322 and NCI – HOP 62 etc). The compound also inhibits the growth of human melanoma (LOX-IMV). In most situations its effect is mediated by the inhibition of CRE or AP – 1 mediated gene transcription.

Septicine is an indolizine alkaloid that displays cytotoxic behavior toward several cancer cell lines (HeLa, Hep G2, MCF-7 and many others) along with imposing the anti-inflammatory activities.

Non-alkaloid components → Quercitin, α – & β – amyrins, Kaempferol, Octasanoloctacosanoate, Tetratriacontanol, β – sitosterol, Stigmasterol, cortisone, Tannins, glucose and minerals.

Leaves – It synthesizes almost similar ingredients alkaloids, flavonoids, steroids, glycosides, tannins, amino acids, proteins and other ingredients like starch, glucose and minerals.

Alkaloids – Tylophorine, Tylophorinine, Tylophorinidine, 3 – O methyl tylophorinidine and Septicine.

Non-alkaloid components – flavonoids (Quercitin, Kaempferol and few other of same categories), steroids (Amyrins, Sitoterols etc), proteins, aminoacids and minerals.

Roots – The components are very same as above.

Pharmacological effects – The various plant extracts provide versatile medicinal and pharmacological actions which are highly beneficial for curing several chronic diseases.

Anti-inflammatory, Anti-allergic and Anti-asthmatic effect – The actual pathophysiology of asthma is the airway inflammation. Along that process, T-helper 2 cells generates several inflammatory cytokines (IL-4, -5,-6, -9, -10 & – 13) that eventually stimulates the process causing growth, differentiation as well as the recruitment of mast cells, eosinophils, basophils and B cells which are engaged in humoral immunity, inflammation and immunity. From the time of Ayurveda, Tylophora Indica / Indian Ipecac has been successfully used to curb this chronic inflammatory status. The large reserve of phenanthroindolizidine alkaloids are identified afterwards enabling to control the condition. Among them Tylophorine and Ficuseptine – A, are seen to be the most potent.

Both of them efficiently prevent the production of NO and iNOS. Experiments show that Tylophorine inhibits the production of inducible TNF – α, iNOS and COX- II. The common promoters of iNOS and COX-II are NF – κβ and AP -1. The activation of later one is inhibited by Tylophorine. It also inhibits mitogen activated extracellular signal regulated kinase -1 and downstream signaling activation of NF – κβ and AP -1. On the other hand, Ficuseptine prevents expression of pro-inflammatory mediators involved in the signaling ways. Additionally, those alkaloids stabilize the sensitized mast cells from degranulation effect thus disallowing the release of Histamine, a potent mediator of inflammatory pathway. The action is better that Chromolyn (di-sodium chromoglycate), a common anti-asthmatic drug works by blocking the surface Cl^– channel. The mechanism presented is involved in controlling bronchial inflammation leading to enhanced mucus formation producing hyper-responsiveness commonly termed as asthma. It is a multifunctional disease involving genetic, allergic, environmental, infectious and nutritional aspects. It may be also related to emotional status of a person. The anti-oxidant flavonoids and phytosterols and Vitamins plus unsaturated fatty acids present in TI also provides help regulating the chronic asthmatic symptoms or else the airway inflammation.

Anti-cancer – Owing to its unique production ability of phenanthroindolizidine alkaloids, TI extract is famously known as a source of anti-cancer medicines for being cytotoxic (IC₅₀ ~ 0.89 – 1.4 µg / ml) only toward the cancer cells. Laboratory experiments on both in vivo and in vitro verify the fact that extract from leaves and stems are cytotoxic to numerous carcinomas but not to any normal cells. Among the identifiable compounds, Tylophorine, Pergularinine and Tylophorinidine are seen vastly effective. It is already known that vascular endothelial growth factor (VEGF) stimulates endothelial cell proliferation, migration and tube formation and angiogenesis. Tylophorine and others interact with the vascular endothelial growth factor receptor – 2 (VEGFR2) enabling to block the angiogenesis which is a major event of cancer progression.

Studies further indicate that Tylophorine analogs arrest the cancer cells at G1 phase also down-regulates Cyclin A₂ expression in Hep G2 cells. Additionally, the alkaloids inhibit dihydrofolate reductase (IC₅₀ ~ 40 nM for Pergularinine and 32 nM for Tylophorinidine), an enzyme which is a key target in most cancer therapy. At or near 75 – 95 nM concentration they fully neutralize the enzyme actions, which is reversible by nature. Experiments further reveal that Tylophorine along with Doxorubicin potentiates apoptosis in human breast cancer cell line, T47D. Tylophorine alone also upregulates the expression of pro-apoptotic proteins (Caspase 3 & 9). It prevents accumulation of cancer cells at G2/M phase. But adding Doxorubicin it further enhances the apoptotic behavior while modulating cell cycle also affecting the expression of Caspase 3 and 9. About ~ 65 % inhibition of cell proliferation is observed in the case of human breast cancer cell line MCF-7 (IC₅₀ ~ 90 µg / ml).

Diuretic property – Both aqueous and alcoholic extract of TI leaves induce diuretic effect when studied in laboratory rats. The increase of both anions, cations and urine volumes are noticed during excretion. The ratio of Na⁺/ K⁺ lays within 2.04 – 2.18 (normal = 2.05 – 2.83). The level of aldosterone is decreased if the ratio drops below the normal range within plasma. Besides the increase of Na⁺ and K⁺ level, Cl^– excretion is also enhanced. The exact mechanism behind its diuretic role is not fully understood. However, seemingly, the effect has been hypothesized possibly due to the inhibition of tubular reabsorption of water and accompanied ions.

Hepatoprotective effect – Experiments using CCl₄ induced hepatotoxicity in albino rats, the methanolic extract of TI leaves show significant hepatoprotection as seen due to lowering of serum hepatic enzymes (glutamate oxalto-acetate transaminase, glutamate pyruvate transaminase), total protein and bilirubin. The effect is somewhat better than Silymarin, a powerful flavonoid (exists in diastereomeric form A & B) which inhibits P-glycoprotein mediated cellular efflux also acts as strong free radical scavenging agent. The histopathological studies also support the fact. The presence of anti-oxidants acting as free scavenging agents could be liable for this action.

Anti-hyperglycemic and anti-hyperlipidemic effect – The methanolic extract of TI leaves can exert hypoglycemic effect as well as lowers LDL, triglyceride and cholesterol. However, it enhances the level of HDL and reduces bilirubin and creatinine in plasma. The lowering of blood glucose could be due to stimulated release of insulin from the pancreatic β – cells and the effect is comparable to the drugs belonging to the category of sulfonyl urea.

Miscellaneus effects –

1. Antimicrobial, antifungal and antiparasite action of TI extract.
2. Strong antioxidant and free radical scavenging ability.
3. Strong immune-modulatory action owing to the presence of alkaloids in the leaf extract.
4. Antistress and anxiolytic effect – The effects are comparable to the normal medication, Diazepam which acts while enhancing the action of GABA, promoting its binding to the receptors that exists as multi-subunit ligand-gated chloride channels thereby facilitating the action of GABA in brain.

Clitoria Ternatea / Asian pigeonwings / Blue pea / Darwin pea / অপরাজিতা

General features: It is a perennial herbaceous plant with non-woody stem displaying flowers of distinctive bright colors, violet, deep or light blue with occasional white markings. Some exist in complete white color also. The botanical name is Clitoria Ternatea (CT) since the appearance of flowers resembles to female vagina (clitoris). Its genus is also named that way, Flos Clitoridis ternatenbus by a German botanist, Rumpf while working for the Dutch East India Company in Malaysia around1678. In English the plant is called Asian pigeonwings, Blue pea or Darwin pea. In Bengali it is commonly known as Aparajita (অপরাজিতা). The plant belongs to Fabaceae family. The flowers are ~ 1.6 inches long and ~ 1.2 inches wide. It grows as vine / creeper in moist condition under tropical environment. The fruits are flat pods about 2 – 3 inches long holding 6 – 10 seeds inside. The pods are edible when tender. The leaves are elliptical or obtuse in shape. It is often used as ornamental plant in the household garden. The plant is a legume, so its roots are involved in symbiotic process with the bacteria in soils transforming atmospheric Nitrogen to use for plant like nitrogen fixing. In a way it improves also the soil quality. CT is a native of South East Asia and largely abundant in the entire Indian subcontinent. It also grows in Australia, Africa and some parts of USA. Its medicinal role as memory, learning and behavior enhancer is widely recognized for a long time. In recent days numerous other medicinal role are also discovered.

Uses: Both flowers and tender pods are used for foods in many Asian countries. Particularly, flowers find applications for the food coloring purposes. In Malaysia they are used to color the boiled rice adding bluish tint which is used along with other delicacies. Commonly, it is used to color the drinks like lemonade or gin. In acidic condition especially in presence of lemon juice it changes to attractive purple coloration. In Vietnam and Thailand this blue drink is common. The flowers are further used as tea and served after mixing with honey and lemon displaying nice purple color. In India, Myanmar and Thailand CT flowers are fried after dipping in the batter. The young pods and leaves are normally eaten as vegetable. Commercially in South East Asia, flowers are used to color the gin which is kept in the dark to preserve its color. The other uses of CT is for animal fodder of the domestic cattle particularly the dried legume. Besides the food uses, roots, leaves and stems of CT are used in traditional Ayurvedic medicine for its strong influence on the central nervous system as a nootropic agent. In addition to enhancing the memory or cognitive senses, it works as antidepressant, also acting as anxiolytic, tranquilizing, anti-pyretic, and analgesic and anticonvulsant agent. It is further claimed to boost sexual urge for the female but no scientific data is yet to be established. The ripe dried and powdered seeds are aperient thus used as a laxative. The roots are bitter in taste and have diuretic, anthelmintic and laxative properties as well. It could be useful against bronchitis, asthma, pulmonary tuberculosis, leprosy, inflammation, ascites and fever. The aqueous extract of flowers is used in treating several eye problems. Below is the table for several medicinal uses.

Folk Medicinal uses

Plant part	Extract	Activity
Roots & Aerial parts	Aqueous or Alcoholic extract	Learning and memory enhancement. Increases Acetylcholine content within neurons. Antimicrobial growth.
	Methanol extract	Nootropic, anxiolytic, antidepressant, tranquilizing, sedative, Anticonvulsant, anti-stress, vascular smooth muscle relaxing, anti-pyretic and diuretic effect.
Roots	Methanol extract	Anti-inflammatory, analgesic, anti-pyretic and diuretic effect.
Flowers	Ethanol extract	Inhibiting platelet aggregation, vascular smooth muscle relaxing and anti-diabetic effect.
Seeds	Ethanol extract	Insecticidal, growth, antimicrobial, anticancer and calming effect on CNS.

Chemical components: Varieties of phyto-chemicals are identified and isolated from CT in roots, stems, flowers and leaves that includes triterpenoids, flavanols, anthocyanins and steroids and their glycosidic derivatives. In addition to those CT synthesizes cyclic peptide, Finotin which has powerful insecticidal and anticancer property.

Finotin – cyclic peptide inter-bridging with cysteine residues having strong anti-microbial effect.

Roots – It contains high level of Indole acetic acid, kinetin and gibberellic acid, a pentacyclic diterpene plant growth hormone. In fact all of them are largely involved during plant growth. Due to high content of Indole acetic acid, it is logical to assume that large reserve of tryptophan exists within the CT root. The root also synthesizes other amino acids including γ – amino butyric acid (GABA) which is considered to be an important inhibitory neurotransmitter.

Roots also have few pentacyclic triterpene like Taraxerol and Taraxerone. Several antimicrobial flavonoid glycoside have been isolated from the extraction of ethyl acetate.

Seeds – It contains significant amount of proteins and polypeptides. One of them is very identical to insulin except having few amino acids differences within the sequence. Uniquely, the seeds also synthesize Finotin, a cyclic insecticidal peptide. Among the protein reserve, some of them have shown anti-trypsin activity. The seeds also have considerable amount of fatty acid like stearic, linoleic, and linolenic and oleic. It also produces water soluble antioxidant components like anthoxanthin / anthocyanin glucosides eg, Delphinidin 3, 3`, 5`-triglucoside which is used as food dye. Additionally, it also shows the presence of p-hydroxycinnamic acid, γ – sitosterol, rutin and adenine and their glucoside derivatives.

Leaves – It contains essential oils, phyto-sterols and flavonoids which mostly exist with glycosides linkage. The other constituents are β – sitosterol, Kaempferol and its various glycosides like Clitorin. Additionally, it has several lactones like Aparijitin which is δ – lactone of 2-methyl-4-hydroxy-n-pentacosanoic acid. An important alkaloid, Oxymatrine has been recently identified in the leaves of CT. It has profound impact on cardiac tissues, preventing cardiac fibrosis (formed by excessive collagen – I and III expression on cardiac tissue), preventing cardiac ischemia, arrhythmia, heart failure and myocardial injuries. The compounds are highly effective against Hepatitis B and C. The mucilage in CT leaf is composed of methyl-pentosan, anhydro-pentosan, and anhydro-galactan.

Flowers – The blue color is due to the presence of anthocyanins, Terantins which have been identified to exist in five forms (A1, A2, B1, B2, D1 and D2) with different grades of glycosylation of acylated, malonylated glyco-derivative of Delphinidin. In addition to those it has Quercitin, Myricetin and Kaempferol. All of them are glycosylated using either glucose or rhamnose sugar chains.

Pharmacological effect: The plant is long known for its potent neuro-pharmacological activities like, elevation of acetylcholine content within CNS tissues which helps enhancing the memory and cognitive function. Besides acting as nootropic agent, it can reduce stress, anxiety also offering as tranquilizing action. Further, CT enables to lower depression and anti-convulsant effect. Besides the effects on neurons, CT shows other beneficial effects acting as anti-diabetic, anti-pyretic, anti-tumor and anti-microbial agents.

Effect on learning memory, general behavior and anxiety – Oral administration of CT root extract dose-dependently enhances the memory in laboratory rats without altering general motor activity. The experiments indicate marked improvement regarding retention and spatial learning behavior within neonatal rats in their growth spurt period. It is proven that the aqueous root extract affects the neuronal structure within hippocampus and amygdala which are related to the learning behavior and memory. The treatment brings permanent change improving memory and learning process. Additional results indicate that CT affects neurogenesis and synthesis of neurotransmitter like Acetylcholine which could be underlying cause behind those effects. Besides involving in neurogenesis within amygdala, the extract enables to stimulate the release of other neurotransmitters helping the overall events. The most anxiolytic effect is noticed when aerial parts of the plant is extracted with methanol.

Antidepressant and tranquilizing effect – The oral administration of methanolic extract of aerial parts shows identical results comparable to chlorpromazine distinguished by the tranquilizing action, dosedependent inhibition of alertness, reduction of spontaneous motor function and sedation. But no catalepsy has been noticed. Its antipsychotic behavior is somewhat different than chlorpromazine which acts as dopamine, serotonin and histamine antagonist. In laboratory rats, at high doses the extract potentiates barbiturate induced sleeping behavior, almost identical to chlorpromazine.

Anti-stress and anticonvulsant effect – The anti-stress effect is noticed by using methanolic extract of the aerial parts of CT. The experiments are conducted using cold- restraint stress induced ulcers in rats, lithium induced head twitch, clonidine induced hypothermia, haloperidol induced catalepsy and NaNO₂ induced respiratory arrest. In case of ulcers, the extract is considerably effective to reduce the effect following dose-dependent manner. As per the number of head twitching by Lithium CT lowers it significantly. Experiments further indicate providing a link between cognitive impairment and serotonergic transmission. The extract is unable to reverse the Clonidine induced hypothermia also failed to reduce the effect of NaNO₂. On the other hand it potentiates haloperidol induced catalepsy but no so significantly. Regarding the anticonvulsant act using maximum electroshock seizures and pentylenetetrazole test on rats the CT extract shows not so significant effect but only to delay the onset of convulsing effect.

Anti-inflammatory, analgesic and antipyretic effects – The methanolic extract of roots have shown considerable anti-inflammatory, analgesic and antipyretic effects in laboratory rats. The effect is seemingly due to its action on COX-1 & – 2 inhibition. The analgesic effect is somewhat insignificant. The antipyretic effect is very comparable to acetaminophen. A number of flavonoids including Terantins are majorly liable for these effects.

Antidiabetic effect – The antidiabetic property is noticed in the ethanolic extract of flowers. After three weeks of oral administration in diabetic induced rats the serum glucose level becomes significant low. The underlying cause is thought to be due to the inhibition of β – galactosidase and α- glucosidase activities but not β – fructosidase. In addition to flavonoids a few peptides are seemingly the underlying cause.

Inhibition of platelet aggregation – The anti-thrombolytic effect is possibly due to the action of Terantins. The effect has been noticed in both in vitro and in vivo. In later case it is more pronounced. The production of Prostacyclin could be the actual inhibitory cause although the other falvonoids also have the similar kind of role.

Antimicrobial effect – The potent antifungal activity of CT toward numerous pathogens is owing to its production of small polypeptide, Finotin. In addition, a flavanols glycoside isolated from ethyl acetate fraction from root shows strong antimicrobial effect against various fungi and bacteria.

Anticancer activity – It is noticed that aqueous or methanolic flower extract exerts anti-proliferative effect on various malignant cells like breast cancers (MCF – 7, MDA-MB-231), human ovarian cancer (Cacov – 3), human cervical cancer (Hela), human liver cancer (HepG2) and human foreskin fibroblast (Hs27). Although no exact component is identified but the presence of pentacyclic triterpenes like Taraxerol, Taraxerone and other sterols could be the real possibility. Interestingly, the isolation of cyclotides (circular mini-peptides) from CT have demonstrated potent anti-tumor activities. Additionally, they exert strong chemo-sensitizing ability. Below is the example of few cyclotides from CT used in anti-proliferative experiment on different cancer cells. For example, in paclitaxel resistant human lung cancer, A549, few cyclotides reduce significantly the level of IC₅₀ and potentiates the effect of Paclitaxel. Similar acts are noticed in case of doxorubicin resistant MCF7/ ADR. The co-exposure considerably enhances the effect of doxorubicin multi fold. Uniquely, the efficiency largely depends on their charges; higher is seen to be the better.

Experiments establish the fact that underlying cause is due to the membrane permeabilization role of cyclotides producing leakage on the cell surface allowing the drugs penetrate freely or making more active. Additionally, membrane disruption also inflicts harm to the tumors.

Toxicological aspects: Toxicological assessment are made using samples prepared by numerous ways of extraction. Usually the dried extracted samples are used for the evaluation in a dosedependent manner. In any cases even at hefty doses no lethality or any significant undesired events have been noticed.

Plumbago Zeylanica / Chitraka / Wild leadwort / Chitra / চিত্রা।

General features: The botanical name is Plumbago Zeylanica (PZ) which in English is commonly known as Wild leadwort. It is medicinal as well as a perennial flowering plant. The plant grows in three varieties producing white, red and blue coloring flowers. The blue flowering plant is named Plumbago auriculata whereas the red one is branded as Plumbago Indica. All of them belong to Plumbaginaceae family. Besides the flower color, the major phyto constituents among them are quite the same. In Hindi PZ is named Chitraka whereas in Bengali it bears almost similar connotation, Chitra (চিত্রা). It is fairly available in the Eastern region of India even in West Bengal. PZ is herbaceous perennial plant that grows all around the tropical and subtropical regions of globe particularly in many places of India especially in the forest of Uttarakhand also in New Guinea area of Australia. Basically all the types show pantropical distribution. In tropical climate, it grows mostly within the monsoon forest. In Mediterranean areas, it is seen to grow by climbing the trunks of large olive / Olea trees. All types of Plumbago are often used as house plants for ornamental reason. The plant has glabrous stems which are prostrate or erect trending to climb upward. It reaches 3 – 4 ft at the mature stage. The leaves are petiolate and appears as ovate, spatulate or oblanceolate blades measuring 2 – 4 x 1 – 1.5 inches in length with glandular, viscid rachises. The flowers are bisexual having white, blue or red corollas and 0.5 – 1.0 inch diameter whereas the tubes are 0.3 – 1.2 inches in length. They are terminally arranged. The capsules are ~ 0.5 inch long containing reddish brown seeds. The fruits have single seed of ~ 0.1 – 0.2 inch in length with reddish brown to dark brown color.

The name ‘plumb’ stems from the meaning ‘lead and agree to convey’. It is why the name Wild leadwort has been originated. All varieties are effective for the digestive and carminative role according to Ayurveda. The plant and roots are noticed to be extremely effective for cardiac, hepatic and neuronal disorders. In rural condition, it is used as phyto-remedy during lead, cadmium and mercury poisoning, particularly the root which is seen more effective. The roots of PZ is a large reserve of phytochemicals, which are immensely important to cure or prevent a good deal of dreadful diseases. One such important one is Plumbagin, a napthaquinone derivative (5-hydroxy-2-methyl-1,4-napthaquinone) superbly effective against various cancers and tumors. The root extract exhibits antioxidant, antiseptic, antipyretic, antimalarial, antiinflammatory, anticarcinogenic and antibacterial properties. The compound helps treating gonorrhea as well as tuberculosis. It also exhibits antifertility, neuroprotective and anti-atherosclerosis activities. Together with Juglone (compound in Almond) Plumbagin turns highly toxic as well as genotoxic inflicting serious DNA damage. Plumbagin is a potent inhibitor of growth and metastasis of hormone refractory prostate cancer.

Folk medicinal uses: In many parts of rural India, the plant is used to treat chronic respiratory problems including bronchitis, asthma, cold and cough. It is further applicable also toward tuberculosis. It exerts significant febrifuge action. The plant is known to help alleviate rheumatism and works against indigestion and dyspepsia too. In addition, it has the ability to stimulate appetite and cures intestinal and liver problems even enabling to control diarrhea. It is able to destroy the various intestinal parasites and worms. In many African nations, it is used to cure influenza and black fever. The herb is famously known for its antiinflammatory role and can remove the headache. It also cures leprosy and related sores. It is useful to treat leukoderma. The plant is good for treating ringworm, scabies and several other skin diseases. In many places of the world it is used for inducing abortion. It is further used to treat hormone refractory prostate cancers. The constituents within herb has potent anti-fertility and anti-hyperlipidemic properties.

Phytochemicals:  The major phytochemical within PZ is Plumbagin which is synthesized at high level in roots, seeds and leaves. Below is the description of various phytochemicals in different parts of plant.

Leaf – Plumbagin, Plumbagic acid, β – sitosterol, 4 hydroxy benzoic acid, Trans – cinnamic acid, vanillic acid, Indole – 3 – craboxaldehyde, 2, 5 –dimethyl-7-hydroxy chromone, Vanillic acid.

Flowers – The white flowers of PZ contains Plumbagin, Glucose and Zeylanone which is actually natural dimer of Plumbagin.

Stem – Plumbagin, Campesterol, Sitosterol, Stigmasterol, Isozeylanone and Zeylanone.

Seed – It contains high concentration of Plumbagin, Linoleic acid, Palmitic acid etc.

Root – It has enormous quantities of different types of phytochemicals viz, Napthaquinone, Coumarin, Plumbic acid and others including several enzymes and aminoacids. Below is the categories structures of those phyto-compounds. Among those varieties, various forms of naphthaquinone derivatives exist in large quantities.

Facts about plant derived Naphthoquinones: The large diversity of napthaquinones can be found within the natural products from plants. Following several different metabolic pathways plants synthesize large varieties of napthaquinones and anthraquinones also, which have numerous pharmacological roles particularly pointing out the nature of scaffolds to develop any novel drugs to prevent or cure dreadful diseases. Normally, most of the napthaquinones and its derivatives possess potent cytotoxic properties which could be due to their ability to generate reactive oxygen species (ROS) which in turn interferes the pathway of cellular respiration. Additionally, DNA is considered to be another target to induce cytotoxic actions via the direct interaction producing covalent adducts. Below is the schematic display of DNA alkylation and redox reaction and subsequent other intracellular effects. Essentially, Napthaquinones via oxidation or alkylation inflicts damage bringing the ultimate cell death. The signaling target can be triggered at lower concentration causing less extensive damages. The compounds stimulate RTK signaling via stimulation of ERK^MAPK and Cx43 phosphorylation affecting intracellular as well as intercellular signaling responses. Further, whether napthaquinones can affect GJIC (gap junctional intercellular communication) in ways other than connexin phosphorylation remains undetermined. But it is noticed that stress-responsive mechanisms of posttranscriptional regulation of connexin levels are altered by these compounds.

[PTPase – protein tyrosine phosphatase, RTK – receptor tyrosine kinase, GJIC – gap junctional intercellular communication].

Picture showing the mechanisms for covalent modification of target proteins. In the process cysteine thiolate is possibly oxidized by the ROS generation via redox cycling to form cysteine sulfenate, sulfonate or bridging ultimately while creating disulfide bonding. In that measure all napthaquinones and its subsequent derivatives are considered to have potent medicinal role.

Pharmacological activities: PZ extracts display different medicinal and pharmacological properties, some of them are already known from the ethno-medicinal folk uses. Afterward almost all of the early day’s findings are verified through the laboratory experiments.

Antiinflammatory and wound healing effect – The plant extract can efficiently reduce edema and the effect could be comparable to aspirin. Laboratory experiments on Carrageenan induced rat paw model indicates that methanolic extract of PZ roots can reduce the edema ~ 63 %. And the effect is dosedependent. One of the ingredients which could be responsible behind the antiinflammatory effect is Plumbagin. It enables to suppress the activation of NF – κβ leading to exert antiinflammatory effects. Further, the methanolic extract shows additional wound healing property.

Memory inducing and CNS effects – Experiments conducted while inducing amnesia for studying the learning behavior and memory by intraperitoneal administration of scopolamine, an anticholinergic drug indicates that CHCl₃ extract of PZ root can reverse the effect quite significantly. Uniquely, the prior treatment with this extract prevents the scopolamine induced effect. The major components of the CHCl₃ extract contains quinones, steroids and terpenoids. The identified suspected components are Plumbagin and its related products like Juglone which efficiently blocks the enzyme acetylcholinesterase enhancing the level of acetylcholine within synapse helping the learning efficiency as well as memory. In that perspective the herb may assist Alzheimer’s’ patients for delaying progression of disease. On the other hand, the hydro-alcoholic extract enhances the dopamine and its corresponding metabolite homo-vanillic acid within the brain striatum that also significantly increases the spontaneous locomotor actions.

Antidiabetic effect – The alcoholic extract of root displays strong antidiabetic property when orally administered it increases hexokinase activity while decreasing the glucose-6-phosphatase activities in Streptozotocin (STZ) treated diabetic rats. Studies further indicate that antidiabetic effects could be due to the effect of Plumbagin on the translocation of GLUT4 in STZ-induced rats.

Blood coagulation activity – The identical effect of Plumbagin or PZ extract has been noticed in terms of blood coagulation. Either the extract of PZ or Plumbagin efficiently reduces the platelet adhesion leading to hemorrhagic behavior. Seemingly, Plumbagin or other napthaquinones in PZ extract potently antagonizes the action of endogenous Vitamin – K thereby allowing the hemorrhagic tendency to prevail. Structure factor analysis shows that Plumbagin works as a competitive inhibitor.

Lipid metabolism action – In animal experiments using hyperlipidemic rabbits, the ethanolic extract of PZ roots cause substantial reduction of total cholesterol, LDL and triglyceride levels. The co-administration of PZ with Vitamin E brings even further reduction. The possible responsible component is Plumbagin which alone enables to reduce the serum and LDL – cholesterol ranging from 53 – 86 % and 61 – 91 %. It also lowers cholesterol: phospholipid ratio by ~ 46 % and in turn enhances the HDL- cholesterol significantly.

Anti-fertility effect – The aqueous-alcoholic extract of PZ leaves exerts potent (~95 %) anti-implantation role owing to the anti-estrogenic behavior that antagonizes the action of estrogen leading to the structural and functional changes of uterus. The effect is caused by the decrease of glycogen content, thickness of endometrium, myometrium, reduction of uterine lumen, pits and folds, number and size of uterine glands, vaginal openings and cornification. It is further noticed that acetone-ethanol extract is more effective in that respect. It is also viewed that it prolongs diestrous stage of the estrous cycle causing temporary inhibition of ovulation. So extract is an excellent family planning agent. Since it acts as a good anti-implantation agent interfering progesterone synthesis and subsequent utilization. It has been indicated that Plumbagin and few other components are liable for this effect.

Anticancer effect – Previous works indicate that alcoholic extract of PZ roots produce considerable anticancer activity when tested against Ehrlich ascites carcinoma implanted in the laboratory animals. It also reduces the elevated level of lipid peroxidation, possibly due to large reserve of terpenoids and flavonoids. Works on Plumbagin alone show further that the compound can inhibit cell proliferation of APL (acute promyelocytic leukemia) – NB4 cell lines dosedependently. The cells undergo apoptosis, morphologic changes, chromosome condensation and apoptotic body formation which are verified by means of light and transmission electron microscopy. The cell cycle analysis show that Plumbagin can arrest the cells at G2/M phase. In addition to Plumbagin, other components like β – sitosterol and its derivatives, Lupenone, Lupeol, Trillinolein from the aerial extract also induce cytotoxicity toward MCF-7 (breast cancer cell line) (IC₅₀ ~ 1.28µM) and Bowes (Human melanoma) cells (IC₅₀ ~ 1.4µM).

Anti-anaphylactic effect – Laboratory experiments show that PZ stem extract dosedependently inhibits the anaphylactic shock induced on mice by the compound 48/80. In addition, it prevents cutaneous anaphylaxis and skin reactions produced by histamine and serotonin on rats. The modulatory activity of PZ or plumbagin is studied on peritoneal macrophages of BalbC mice while using against Staphylococcus aureus. The study shows that both increase the bactericidal activity along with hydrogen peroxide and superoxide anion release. The study thus concludes that the effect is modulated by the release of oxygen free radicals.

Antiviral activity – The methanolic extract of PZ roots exerts potent antiviral effect when tested against influenza A, coxacki virus B3, herpes simplex type 1 Kupka.

Antioxidant activity – The antioxidant actions of hydro-alcoholic extract and many of its isolated components are studied by free radical scavenging methods. The extracts and many of the identifiable components like Plumbagin or its derivatives can significantly inhibit lipid peroxidation induced by cumene hydroperoxide, ascorbate-Fe⁺² and peroxynitrite.

Antibacterial effect – The chloroform extract of PZ roots show strong antibacterial actions against most of the known bacteria eg, E coli, Salmonella typhi, Staph aureus, Klebsiella pneumonia, Bacillus subtilis and Proteus vulgaris and Pseudomonas aeruginosa.

 

Boerhavia Diffusa / Red spiderling / Punarnava / পুনার্নভ ।

General features: It is a flowering plant of ‘four o’clock family’ (Nyctaginaceae). Besides holding the name Boerhavia diffusa (BD), the plant is also called ‘Red spiderling’ in English. In India, BD is commonly known as Punarnava (পুনার্নভ) meaning ability to rejuvenate the body and soul as suggested by the reputed ancient Indian apothecary, Ayurveda. It is a plant with diffuse inflorescences. The inflorescence occurs at end of each branches and forked about 3 – 6 times. The branches are divergent ending with 2 – 5 flower clusters. The leaves are ~ 0.4 inch long simple opposite, short petioled, ovate-oblong, acute or obtuse, subcordate base glabrous above. Flowers are small pale rose in color. Fruits are highly viscid, easily detachable and one seeded. The bract at flower base is lancelike ~ 0.3 – 0.4 inch. The name ‘four o’ clock’ is derived for the flowers since they open in the afternoon and close at morning. It is this natural behavior that provide the name. The flowers grow with white, yellowish shades, pink to red or even spotted with other shades. The plant belong to Boerhavia genus. It has approximately 45 species belonging to this class. One of the species among them is Boerhavia diffusa which grows small red flowers with a touch of pleasant smell. In India and in many places of South East Asia BD is used as vegetable green. Additionally, it is often used as a pain medication. The plant grows mainly in tropical and subtropical climates like in India, Pacific island nations, Caribbean islands, South Asian nations, Latino countries and Southern parts of US. It is often characterized as weed. It is a perennial herb with stout root stock holding multiple branches. The herb is widely reputed mainly for its antiinflammatory and analgesic actions. In tribal inherited places of India, the roots are routinely used to treat various hepatic disorders and internal inflammations. In recent days, it is seen effective in treating edema, ascites and early stages of liver cirrhosis and peritonitis as well. Usually the whole plant or its roots or their extracts are used for treating several serious ailments. Although frequently used as vegetable in many places, the plant contains slight bitter or astringent taste.

Medicinal properties and uses: The extracts of whole plant or its roots and leaves possess anthelmintic, diuretic, cardiac stimulant, diaphoretic, emetic, expectorant, febrifuge, laxative, anti-inflammatory and aphrodisiac properties. The herb can be used in all cases of inflammations. It is also effective against strangury, leucorrhea, opthalmia, myalgia and scabies. The extract helps prevent dyspepsia, constipation, cough, bronchitis, jaundice, cardiac problems and anemia. The numerous studies on animals suggest that the herb has potent anti-proliferative effects on varieties of cancer cells also enabled to prevent their metastasis. The most effective component in this regard is Purnavarine / Lunamarine, which is a quinolone alkaloid. The compound also exhibits antiesterogenic, immunomodulatory and anti-amoebic property.

Chemical components: The herb is a good source of amino acids within roots and plant bodies. Additionally, BD has several fatty acids both saturated (38 %) and unsaturated (6.5 %).  The plant contains few vitamins eg, C (45 mg), B₃ (100 mg) and B₂ (22 mg) (per 100 g). The level of Calcium is ~ 175 mg. The other important chemical components are β – sitosterol, Ursolic acid, stearic and palmitic acids, arachidic acid, boeravinone A to F, boerhavic acid, borhavine, campesterol, dauscosterol, ecdysone, flavones, and hypoxanthine. The plant synthesizes large reserve of flavonoids and isoflavonoids / rotenoids or rotenone. Rotenone inhibits mitochondrial electron transport property thus often used as pesticide or insecticides therefore toxic by nature. But the toxophore of Rotenone structure is phenyl derived ring and two – OCH₃ substitution on the first phenyl ring. But those identified in BD are nontoxic because of the lacking of isoprenoid residue on D ring or having either unsubstituted or monosubstituted ring A. The major rotenoid in BD is boeravinone B which is ~ 0.005 %.

The rotenoids from BD show strong anticancer and antiinflammatory activities. Additionally, the triterpenes of BD eg, Ursolic acid, β – sitosterol and others also exert versatile beneficial effects on health. For example β – sitosterol is effective against benign hyperplasia also enables to reduce the blood pressure. Ursolic acid is a potent anticancer drug. Campesterol lowers LDL and cholesterol in plasma also precursor to several anabolic steroids. Ecdysone is a molting hormone mostly acts as antifeedant. It also has anti-hyperglycemic, immunomodulatory and hepatoprotective property. Below is the list of several chemical components and their physiologic effects. The compound, ecdysone also acts as anti-stress hormone.

Several important chemical constituents and effects of BD

Types	Name of compound	Bioactivity	Plant part
Phenolic glycoside	Punarnavoside	Antifibrinolytic	Root
C- methyl flavone	Borhaavone		Root
Isoflavone	2`-O-methyl-abroisoflavone
Flavonoid	Quercitin, Kaempferol	Antioxidant	Leaves
Flavonoid glycoside	3,4-dihydroxy-5-methoxy- cinnamoyl Rhamnoside, Quercitin-3-O-rhamanosyl (1-6)galactosides, Euplaitin 3 – O-galactosyl (1-2)glucoside,  Kaempferol- 3- O- robinobioside, Eupalitin-3-O-β- Galactopyranoside.		Leaves
Phenolic acid	Trans-caftaric acid		Roots.
Rotenoids	Boeravinones A, B, C, D, F		Roots
	Boeravinones G, H	Anticancer & Spasmolytic	Roots
	Boeravinones I, J		Roots
	Boeravinones M, P, Q, R, S		Roots
	Cocineones E, B		Roots
	Diffusa rotenoid		Roots
Xanthone	Boerhavine		Roots
Lignan	Liriodendrin	Ca+2 channel antagonist	Roots
	Syringarsinol mono – β- glucoside	Ca+2 channel antagonist	Roots
Purine nucleoside	Hypoxanthine-9-L- arabinofuranoside	Cardiotonic	Roots
Sterol	Boerhavisterol, β-sitosterol, campesterol		Roots
Sterol ester	Boerhavilanostenyl benzoate		Roots
Ecdysteroid	Β – ecdysone	Increase of protein Synthesis, Antidepressant, Antistress, Immunomodulatory, Anti hyperglycemic, Hepatoprotective.	Roots

Chemical structure of several important chemical constituents of BD

Pharmacological effects: BD exhibits numerous pharmacological effects which have been already noticed from its versatile ethno-pharmacological usefulness. The majority of its uses are confined to kidney problems, jaundice, skin problems, healing wounds and inflammation, reproductive problems and eye diseases. Below are some of the facts verified from numerous laboratory experiments.

Anticancer effect – The ethanolic extract of root and leaf show cytotoxicity toward U – 87 MG (malignant glioma cell) and HeLa (cervical cancer) cell lines. Presumably, the major effect in this regard is exerted by the alkaloid fraction having Punarvine causing 40 % cell death. Further purification results in ~ 85 % cellular toxicity or cell death within 72 hours exposure when tested in vitro. It is noticed that Punarvine, the alkaloid isolated from BD can exert antibody dependent cellular and complement mediated cytotoxicity with enhancement of NK cell activity. The alkaloid also increases the production of IL – 2 and IFN – γ. The levels of pro-inflammatory cytokines like IL- α, IL – 6 and TNF – α becomes considerably lowered by its administration. The compound can control lung melanoma possibly by downregulating the expression of MMP – 2, MMP – 9, VEGF, ERK – 1 and ERK – 2 in lung tissue. The extract is also effective in controlling other lymphoma and leukemic cells. Boeravinone G and H are identified to be strong efflux inhibitors of breast cancer resistance protein (BCRP) belonging to the family of ATP binding cassette protein (ABCG2) which is often overexpressed in many cancer cells. BCRP tends to efflux varieties of anticancer drugs. Boeravinone G and H isolated from BD are seen to potently inhibit the efflux activity of BCRP. The isolation of other rotenoids and subsequent elucidation of chemical structures establishes the fact that there is a positive role of – OCH₃ at 6 position of ring B also the absence of a substituent at position 10 also the necessity of 6a/12a double bond between B and C ring.

Antiinflammatory effect – Experiments regarding inflammatory models on laboratory rats show that the BD extract of leaf and flower can exert antiinflammatory effect by reducing ~ 56 % edema inflicted on rat paws. BD is famously known for its anti-inflammatory and analgesic actions. The compounds Liroidendrin, syringaresinol diglucoside, quercitin and kaempferol could be responsible for the antiinflammatory and analgesic effects.

Hepatoprotective activity – In vivo studies using laboratory rats inflicted with several noxious stimuli like carbon tetrachloride or thioacetamide show significant protection or recovery in presence of BD root extract. The levels of SGPT, SAP, triglycerides and total lipid contents are lowered considerably. The histopathological view also supports the fact indicating trend to minimize the fatty cysts in the liver. The root extract by alcohol or aqueous media can provide protection also against paracetamol / Tylenol induced liver injury. The large presence of antioxidants within either extract is proven to be majorly responsible for this potent hepato-protective behavior. Besides present laboratory studies, the ethno-pharmacological reports have already proven that BD root extract is effective against numerous hepatotoxins.

Diuretic and renal activities – The administration of 0.5 – 1.0 % aqueous extract of BD is enable to dissolve and inhibit the struvite crystal growth (composed of Ammonium magnesium phosphate hexahydrate) within urinary canaliculi for women. The dissolution of crystals usually occur within 4 days by the use of 1% extract. Further the extract of aqueous or alcohol also produces significant diuresis. In animal studies on rats, the extract from roots enhances ~ 90 % urine volume whereas the same from leaf or flower causes ~ 63 % increase. Some suggest that the alkaloid, Punarvine and some level of choline components could be liable for this effect. Experiments have further shown that root extract prevents Calcium oxalate crystal formation, considered as kidney stone, urolithiasis. The serum ionic status and renal Na⁺ – K⁺ ATPase activity to increase diuresis could be the underlying reason behind the event.

Antidiabetic and hypoglycemic property – The BD leaf extract (200 mg / Kg) increases plasma insulin level (~ 10.4 µU / ml) which is comparable to 600 µg / Kg of Glibenclamide (~ 9.7 µU / ml). The chloroform extract of leaf can induce hypoglycemia dose-dependently. No specific component(s) has been identified yet.

Antioxidant effect – In vitro studies indicate that BD extract plays a large antioxidant role which could be related to its antiinflammatory, anti-Parkinson and anti- Alzheimer property. The extract has powerful ROS scavenging ability when tested against various free radical generating agents.

Anticonvulsant effect – The extract of BD shows potent anticonvulsant effect when tested on Pentylenetetrazole or Bay-k-8644 induced seizures in mice. The calcium antagonist property of extract is seemingly responsible for this effect. The compound liodendrin is possibly thought to exert the anticonvulsant activity.

Spasmolytic property – The introduction of methanolic extract of BD root on electrically or acetylcholine or histamine or BaCl₂ stimulated isolated rat ileum shows significant spasmolytic actions (IC₅₀ ~ 182 to 158 µg / ml of dried content). The effect occurs due to the involvement of extracellular Ca⁺² ion but not the intracellular. The identified compound is Boeravinone E which is a powerful spasmolytic compound in the extract. Usually, the non-prenylated rotenoids are also the effective spasmolytic agents.

Antifungal and antimicrobial actions – The ethanolic and aqueous extract of whole plant shows powerful antimicrobial effect against number of bacteria. The minimum inhibitory concentration is 125 – 150 µg / ml. It works on both Gram positive and negative types. Its antifungal activity is noticed for ethylacetate extract for various fungi inhibiting 79 – 43 % in most of the cases. The alcoholic extract is also effective against tuberculosis, cough, diarrhea, eczema dysentry and urinary tract infections.

Antifibrinolytic action – The root extract of BD shows potent antifibrinolytic activity which is comparable to the usual agents like ε- aminocaproic acid, transexamic acid, naproxen and ibuprofen. The mechanism of action relates to NAD-dependent-15-hydroxy-prostaglandin dehydrogenase activity within the tissue. In that regard BD root is endorsed universally for many gynecological disorders like pain in female genital, regulation of menstruation, irregular high bleeding especially due to IUD insertion inside the uterus. Several phenolic glycoside, particularly Punarnavoside could be the underlying reason behind this effect.

Conclusion: The herb contains versatile chemical constituents that have diverse therapeutic effects offering hepatoprotection, diuresis, antitumor, antiinflammatory and several others. In addition the large reserve of rotenoids and its subsequent beneficial role on different types of diseases might help construct more efficient synthetic mimics to prevent or cure any ailments.

 

Mucuna pruriens / Cowhage / Kaunch / আলাকুশি

General features: The botanical name is Mucuna pruriens (MP). It is a tropical legume plant, originated mainly from Asia and Africa, belonging to Fabaceae family. The seeds are called velvet bean or lacuna bean. In English, it is named Cowhage. In India, it is called Kaunch in Hindi, whereas in Bengali the name is Alakushi / আলাকুশি।. The plant often causes itchiness if touched, especially when the shrub is young, and the itchy behavior is noticed further on the seed pods. Besides its agricultural or horticultural values the plant displays enormous medicinal potential particularly to the Parkinson’s affected persons. MP is cultivated in Southern India, Bahamas and Florida also in some African nations to use as staple foods. The whole plant or dried beans are used from the ancient times as Ayurvedic medicine to treat anxiety, arthritis, worm and hyper-prolactinemia (high prolactin level in the blood) for women. It reduces pain and fever and induces vomiting. It is highly useful to treat Parkinson’s disorder because of large L-Dopamine (Levodopa) content in the beans. In rural India it is customarily used against snake and scorpion bites. MP is often used to treat menstruation disorders, constipation, edema and tuberculosis. It is an aphrodisiac and uterine stimulant. In South and Central America and in few African nations the powdered bean is used as food. The plant is annual climbing vine reaching to ~ 50 ft in length. At young stage it is covered with fuzzy hairs but when grows older it turns almost free of hair. The leaves are green rhombus shaped, ovate or wide-ovate having pointed end. The leaf stems are 0.1-inch-long, and leaves are about 0.5 inch in length. The flower heads are arrayed as panicles. It is about 7 – 14 inches long and have multiple whitish purple flowers. The associated leaves are ½ inch in length. The bell is ~ 0.5 inch long and felt silky if touched. The pods are ~ 7 inches long and 0.5 – 0.8 inch wide. Its husk is hairy that holds 7 – 8 seeds / beans. When ripened the seeds turn shiny black.

Traditional therapeutic uses: Practically, each part of the plant is used for different medicinal needs according to traditional / folk therapy. The leaves are used for treating bone fractures, insanity problems, ring worms, snake and scorpion bites, sores and syphilis. It can be used also as aphrodisiac or for treating dysmenorrhea, amenorrhea, dropsy, elephantiasis and neuropathy. The roots are used to treat cholera, elephantiasis. It has thermogenic action also acts as aphrodisiac, emmenagogue, and anthelmintic. The seeds have multiple therapeutic uses. It acts as powerful antioxidant having hypocholesteremic, antifungal, anthelminthic, abortive and anti-parkinsonian properties. It is also an aphrodisiac, anticancer, immunomodulatory and prevents catarrh, cough, delirium, dropsy, dysentery, impotency and sterility. Its further action is noticed to be a stimulant and is used to treat dysmenorrhea. The seeds can act as nervine, emmenagogue, lithiasis and uterine stimulant.

Chemical constituents: The most intriguing factor about MP is its ability to synthesize L- dopamine (L – DOPA), the most inevitable neurotransmitter of CNS, needed for the normal functioning of motor neurons. The distribution of L – DOPA seems everywhere in the plant but the highest level is noticed within seeds. Besides L- DOPA, the plant also synthesizes 5-Hydroxy tryptamine (5-HT) / Serotonin, another important neurotransmitter identified to control mood behavior and other associated effects. Its existence in hair of the peapods produces itchiness on the touch. Additionally, there is another itching factor, a quinoline alkaloid; 3-acetyl-3 hydroxy-4-ethenyl-6-(N-cyclopent-2-4-dienyl-piperidine) quinoline. Interestingly, the plant also synthesizes several other neuroactive compounds like, Bufotenine, Choline, N-N-dimethyl tryptamine, Nicotine, Physostigmine etc.

Distribution of L- DOPA

Plant parts	% of L – DOPA (dry w / v)
Matured seeds	3.6 – 4.2
Pod-pericarp	0.14 – 022
Leaves	0.17 – 0.35
Stems	0.19 – 0.31
Roots	0.12 – 0.16

Uniquely the plant contains large reserve of alkaloids which are also physiologically active. The seeds have four alkaloids eg, L-3-carboxy-1,2,3,4-tetrahydro-isoquinoline, 1-methyl-3 – carboxy-6,7-dihydroxy-1,2,3,4 tetrahydro-isoquinoline, dimethyl-3 carboxy-6,7-dihydroxy-1,2,3,4 tetrahydro-isoquinoline, dimethyl -3 craboxy-6,7 dihydroxy-1,2,3,4 tetrahydro-isoquinoline and 1-3-carboxy-1,1 dimethyl-7,8 dihydroxy-1,2,3,4 tetrahydro-isoquinoline. In addition to those, the seed extract also has 5 – HT, 5- methoxy – N, N –dimethyl tryptamine – N oxide, 6 – methoxy-harman, behenic acid, β-carboline, β-sitosterol, Bufotenine, choline, gallic acid, indole – 3-alkylamine, linoleic acid, mucundine, mucunain, niacin, nicotine, glutathione, Indole – 3-dimethyl tryptamine, ascorbic acid, squalene, stearic acid etc. The seeds also have phosphorous, aminoacids, polysaccharides and several vitamins. The most intriguing fact is that beans have particular protein (gp Muc) containing seven isoforms (Mw 20.3 – 28.7 KD, PI 4.8 -6.5) with conserved sequence DDREPV-DT, analogous to the soyabean trypsin inhibitor. The administration of aqueous bean extract having this isoforms is extremely effective against the severely toxic African or Indian snake venoms of Echis carinatus, Naja naja, and cobra or similar other kinds while working by following the immunological mechanism via the formation of antibody. The leaves and roots synthesize similar common constituents. The leaf shows L-DOPA, 6-methoxy harman, Genistein or hydroxy Genistein, 5-HT, 5-hydroxy tryptophan, nicotine, N, N dimethyl tryptamine, bufetonine, 5-methoxy-N, N-dimethyl tryptamine and 5-methoxy-N, N dimethyl tryptamine- N-oxide. Additionally, it has several lipids and fatty acids, oleic (7.6 %), squalene (7.9 %), Octadecanoic acid (6.2 %) including ascorbic acid (3.6 %).

Important physiologically active components in Mucuna pruriens

Commonly known physiological actions of Mucuna pruriens

Pharmacologic action	Plant parts	Extraction	Possible compounds
Anti-venom	Seeds	Aqueous	Proteins (gpMuc)
Anti-diabetic	Seeds	Ethanol / water (1:1)	Cyclitols, Oligosaccharides
Antioxidant	Whole plant	Methanol	Phenols & Tannins
Neuroprotective	Seeds & Whole plant	Ethanol / Water (1:1) or Propanol.	L-DOPA, Alkaloids, Amino acids & Isoquinoline Alkaloids.
Antimicrobial	Leaf	Methanol or Propanol	Tannins, Alkaloids & L-DOPA

Pharmacological effects: The plant has enormous physiological role in many diverse ways.

Neuroprotective action and anti-Parkinson effect – It has been claimed that extract of seed or its powdered form is comparably more effective toward the Parkinson’s affected patients than any synthetic analogs of L-DOPA particularly concerning its long-term use. In case of Parkinson’s disorder, the dopamine content within brain undergoes significant reduction due to the lack of conversion of L- tyrosine to L-DOPA. In that situation, the administration of L-DOPA or any of its analog would generally help since it can cross the blood-brain barrier and simultaneously enables to convert to dopamine thereby bringing back the needed neurotransmission. The powder increases brain mitochondrial complex – 1 actions without affecting the total monoamine oxidase (MAO) level for containing NADH and coenzyme Q – 10 which shows therapeutic benefit in Parkinson’s disorder. Additionally, unlike the synthetic L-DOPA the powder treatment restores endogenous dopamine, L-DOPA, norepinephrine and serotonin content inside the brain which might provide further help to the affected patients or help prevent its manifestation.

Anti-venom effect – Interestingly, a purified protein, gpMuc within the seeds has shown anti-venom role against many known snake venoms. The seed protein, gpMuc acts as a poor trypsin / serine protease inhibitor but it does not work directly to neutralize the venoms. Laboratory experiments establish the fact that antibodies generated against gpMuc uniquely cross reacts with the venoms providing the protection while neutralizing it. About 0.16 – 0.19 mg of seed extracts enable to neutralize twice the lethality (LD₅₀) of cobra and common krait venoms. The aqueous extract of seeds has been also tested for different pharmacological effects eg, lethality, phospholipase activity, edema formation, fibrinolytic actions as well as the hemorrhagic actions.

Antibacterial action – The methanolic or propanolic extract of whole plant or its leaves have broad spectrum antibacterial effects which have been already documented against Bacillus cereus, Staphylococcus (gram positive) and Proteus vulgaris (gram negative). The extract is also effective against Erwinia cartovora, Pseudomonas syringae, P. marginalis, P. acruginosa, and Xanthomonas campestris.

Antidiabetic effect – In laboratory experiments using diabetes induced (Alloxan or STZ) rats, the oral administration of aqueous, ethanolic or methanolic extracts of seeds and leaves exert potent anti-diabetic effect. It also lowers the urea, cholesterol and creatinine level in circulation of diabetic animals along with the glucose.

Antioxidant effect – The whole plant, leaves, seeds or roots have abundant quantity of antioxidant phenolic compounds which are measured by the usual procedure using 1,1 diphenyl-2-picryl-hydrazyl. In addition to antioxidant actions, the extracts also exhibit free radical scavenging action. The generation of reactive oxygen species (ROS) causes lipid peroxidation, DNA strand break thus playing many adversarial role in physiology relating to the cardiovascular problems, diabetes and neoplasticity as well. The antioxidant effect of seed extract on Erlich Ascites Carcinoma bearing Swiss albino mice were studied to estimate the liver biochemical parameters like LPO, GSH and antioxidant enzymes SOD and Catalase which shows that extract decreases the level of LPO and increases the Glutathione level, SOD and Catalase indicating the increased antioxidant role of the extract.

Effect on fertility – Consumption of Mucuna pruriens powdered seeds (5g / day) orally for 3 months using single dose to the infertile men shows significant recovery of serum testerone, luteinizing hormone (LH), dopamine, adrenaline and noradrenaline level within those human subjects while simultaneous reduction of follicle stimulating hormone (FSH) and prolactin (PRL). Additionally, there is considering increment of sperm-count as well as the motility. Prior to the treatment, those parameters are observed to be significantly low. Further experiments establish that seed powder can regulate steroidogenesis and subsequently enhancing the fertility by working via hypothalamus-pituitary-gonadal axis. Associated experiments uniquely indicate that this action possibly proceeds by lowering of the stress. It is noticed that reduction of seminal cortisol and lipid peroxide levels are enhanced within the infertile subjects with concomitant lowering of glutathione, ascorbic acid, super oxide dismutase (SOD) and catalase. Treatment with powdered seeds can restore the levels of those parameters in seminal plasma. Seemingly the seeds reactivate the antioxidant defense within the infertile subjects that help manage their stress level thereby improving the quality of semen and sperm count subsequently removing the incidence of infertility.

Aphrodisiac action – The alcoholic extract of MP seeds shows noteworthy aphrodisiac effect in both human and laboratory animals of either sex. It considerably enhances the mounting frequency, intromission frequency and ejaculation latency. The potency test shows increased erections, quick flips, long flips as well as total reflex. It is claimed that the large level of L-DOPA helps recover spermatogenic loss by opposing ROS, lowering of mitochondrial membrane potential also apoptosis. Studies further indicate that either the seed extract or its powder rejuvenates antioxidant defense mechanism and in addition provides help managing the stress while improving the semen quality. In that regard the sperm count along with the motility is raised considerably high in comparison to infertile human and animals. The seeds also substantially enhance the action of libido for any female species.

Antidepressant effect – Besides neuroprotective effect, the other important role of MP is to act as an effective antidepressant owing to large reserve of L-DOPA and serotonin and a few neuroactive alkaloids mostly within the seeds. So either the seed powder or its hydro-alcoholic extract exert profound antidepressant effect. The depression is a symptom of altered mood and cognitive function including persistent thoughts of death or suicide. It is hypothesized that this abnormal situation is caused by the functional deficit of endogenous monoamines (dopamine, serotonin and nor-epinephrine) at particular sites of the brain. A large number of studies are already conducted establishing the role of dopamine on mesolimbic or mesocortical systems relating to lack of motivation, anhedonia and other related symptoms. The neuroprotective and anti-parkinsonian effects of MP are already confirmed.

Anti-tumor, antiproliferative and anticancer effect – In laboratory animal studies, the methanolic extract of MP seeds causes shrinking of tumor volume, growth, survival time of hosts in Ehrlich Ascitic carcinoma bearing Swiss albino mice. The antitumor effect is possibly to be due to its powerful antioxidant action since it increases glutathione, SOD and catalase level subsequently reducing the event of lipid peroxidation. Additionally, the extract also activates the immune response within the mice. The antiproliferative role of aqueous leaf extract has been studied in the case of 7, 12 – dimethyl-benzene-anthracene (DMBA) induced breast cancer in female albino rats. Further, ethyl acetate or methanolic extract from seeds show similar antiproliferative effect on human liver carcinoma cells, Huh – 7. The antiproliferative action has been identified to be due to the presence of alkaloid, 6,7 – dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid. The docking studies indicate that the inhibitory action occurs via the docking of this alkaloid at the active sites of the enzyme Caspase – 3 and 8. The overall affinity of the compound toward Huh – 7 for exerting apoptosis is, EC₅₀ ~ 13.97 µM.

The anticancer effectivity of  different extracts of seeds has been assessed using prostate cancer (GC) and breast cancer (ZR-75) cell lines regarding the cytotoxicity, viability count and growth inhibition. The IC₅₀ values lay within the range of 16 -15 µg.

Antiinflammatory, analgesic and antipyretic effect – Laboratory tests on animal shows that leaf extract exert potent antiinflammatory effect on carrageenan induced inflammation. The effect is somewhat comparable to the non-steroidal antiinflammatory drug, Diclofenac. Although no specific compound(s) have been identified but recently, a lectin (Mw ~ 61 KD) is isolated showing potent antiinflammatory property. The effect is seen to be mediated via the inhibition of COX-1 & 2. Further, the antipyretic effects of several sesqui-terpene lactones as well as tryptamine analogs present within the leaf and seed extract could be responsible to bring down the body temperature of yeast induced fevers in animals. The temperature goes down within 2hours of administration of the extracts.

Effect on growth hormone – The seeds enhance dopamine level within the body thereby stimulating human growth hormone production (HGH) leading to protein synthesis as well as muscle growth. It is an anti-aging component that increases fat burning, elevates sexual performance, improving the skin tone also.

Induction of sleep – Both leaf and seeds can induce sleep by helping reduce stress. L-DOPA supplied by the extracts or powders produces dopamine in brain which acts on the pineal gland releasing melatonin, sleep inducing hormone. The rise in dopamine level thus offers stress relief causing relaxation while inducing sleep.

Miscellaneous pharmacological role – A) Anticoagulant effect; B) Anti-protozoal; C) Anti-fungal; D) Anti-hypercholesteremic; E) Bronchodilator; F) Antispasmodic; G) Anti-radiation; H) Nematocidal; I) Taenicidal (destroying tape worms).

Acorus calamus / Sweet flag /Bach / Vacha

General features: The botanical name of this flowering plant is Acorus calamus (AC), in English it is called Sweet flag whereas in Bengali, it is named as Bach and in Sanskrit it is termed as Vacha. From the early Vedic period, this herb is known to stimulate the intelligence in brain and subsequent behavior of self-expression. Besides the effect of rejuvenation of brain and nervous system, it also stimulates the appetite behavior. In India, the plant is considered as a valued drug since it acts as a rejuvenator. It can reduce the acidity of stomach also at small doses it cures anorexia but at large doses it may induce vomiting. Externally, it is often used to treat eruptions on the skin. Further, it is seen to be effective against dyspepsia and epilepsy. The herb belongs to Acoraceae family of Acorus genus. AC is an important and much appreciated medicinal herb due to its diverse health effects. The word ‘Acorus’ is evolved from Greek ‘Acoron’ introduced by the most celebrated ancient Greek physician, pharmacologist and scientist, Pedanius Dioscorides in his book “De Materia Medica”. That brought the word ‘Coreon’ meaning pupil since this herb was traditionally used to treat eye problems, particularly during inflammation. Afterward, it showed numerous medicinal actions like anti-spasmodic, carminative and anthelmintic effects. It has been in use to treat few neurological disorders like epilepsy and other chronic CNS disorders. It is commonly used for treating fevers, kidney stones, rheumatism, eczema and bronchial infections. The herb is a native of India, Central Asia, Europe and Southern Russia and Siberia. In India, AC grows in the North Eastern states like in Manipur, Nagaland, and Mizoram also on the north eastern Himalayan regions. Some varieties are also cultivated as a precious medicinal plant in the Sothern states of India like Tamilnadu, Andhra and Kerala. According to the ancient Indian Ayurveda, this medicinal herb helps enhance intelligence and improves the speech. The ancient text also claimed its ability to manage the epilepsy, schizophrenia and amnesia. Considering other traditional / folk medicinal uses over the centuries, AC is seen highly effective against digestive disorders and pain. As per its adversarial role, it is also considered to be slightly toxic although no exact clinical data are available. The major parts consumed for medicinal uses are rhizomes but in frequent occasions leaves are also expended. AC is herbaceous perennial plant that grows in the wetland or near any water front and normally reaches to a height of approximately 6 – 7 ft. It has the basal leaves rising from spreading rhizome. The leaves are yellowish-green with slight pink sheathing at the bases. They are sword shaped, narrow and flat, tapering to the long and acute point with parallel veins.  AC can be distinguished from the others of similar kinds due to crimped edges of its leaves. Further, it spreads fragrances if crushed. Interestingly, those growing in wetland or near to water front only bears the flowers. The flower stems are solid and triangular that rise from the axils of outer leaves. The spadix arises from one side of the flower stem which is solid and cylindrical but tapers at the end, approximately 2 – 4 inches by length. The flowers have sweet fragrance. In Europe the flowering continues for about a month during late spring or at the beginning of summer. But it does not bear the fruit. The Asian variety occasionally grows fruits which are tiny berries filled with mucus. After ripening, it drops out and disperses in the water. The cylindrical rhizome is ½ inch diameter that bears numerous fibrous roots below. The color of rhizome exterior is brown but inside is pesky white.

Medicinal uses: The roots / rhizomes or leaves of Acorus calamus are used as a traditional medicine for curing or preventing numerous ailments. It is normally used, 1) to reduce fear and excitement and helping the schizophrenia sufferers, 2) in perfume industry owing to its sweet fragrance of essential oil, 3) to treat rheumatoid arthritis and body pain, 4) as a sedative, 5) for protecting cardiac system, 6) for skin infections like eczema or scabies, 7) to treat epilepsy, deafness and dizziness, 8) to treat constipation, 9) to cure fever, asthma, cold and bronchitis, 10) for its anti-neoplastic effect, 11) to relax muscle, 12) to enhance circulation in brain increasing awareness, 13) as anti-helminthic helping destroy the worms in intestine, 14) as antiviral, antifungal, to treat yeast infection and bacteria as well, 15) to cure colic pain, 16) as mouth freshener.

Adverse effect: The extract or essential oil exerts uterine contractions thus advisable not to use during pregnancy or lactation.

Chemical components and individual physiological role: Approximately 84 chemical constituents or more of different categories have been identified in AC rhizome and very similar in the leaf. There is a large reserve of essential oil having varieties of terpenes and phenolic derivatives eg, (Z) -Asarone (16 – 25 %) and (Z) – methyl-iso-eugenol (2 – 5 %), (E) – Caryophyllene, α – Humulene, Germacrene, Linalool, camphor and Iso-borneol and Cadinenes. In addition to those it has more like Acolamone, Acorenone, Acoragermacrone, Acoramone, Acorone, Calacone, Calcorene, Calamene, Calamenol, Calamone, Calamenone, Calarene and others. Below is the structure and brief description about their respective biological effects.

Salinen type sesquiterpene having sweet fragrance and anti-inflammatory action.

Sesquiterpene having inhibitory activity against Acetylcholinesterase and Butylcholinesterase that helps prevent Alzheimer’s and other cognitive dysfunction.

Powerful analgesic and anticonvulsant component.

Phenyl propenoid component – suspected toxic, euphoric that may cause arousal.

Bicyclic terpene having diuretic and antiurolithiatic effect and helps prevent kidney stone.

Monocyclic terpene showing antibacterial and antiinflammatory effect.

α- Isomer shows antimicrobial property including effects on gram (+) and gram (-) bacteria, Yeast (candida albicans).

Tricyclic terpene having sedative and microbial effect.

Psychoactive compound blocks CNS depression and anti-convulsing effect.

Phenyl propenoid. α- isomer is a hypocholestermic agent and binds to HMG-CoA. β- Isomer is a suspected carcinogen and toxic, providing bitter taste also displaying insecticidal antibacterial and neuroprotective properties.

Phenyl propenoid, inhibitor of Acetyl-cholinesterase, α – glycosidase and α-amylase thus inhibits neurologic disorders like Alzheimer’s etc, acting as starch blockers having antidiabetic activity.

Bicyclic sesquiterpene provides aroma of black pepper binds and activates cannabinoid receptor (CB₂) thus acting as potent analgesic, also a strong antiinflammatory agent particularly acting in brain and CNS tissues, considered to be anti-Alzheimer’s agent.

α-isomer of β-Caryophyllene acting as strong anti-inflammatory agent.

Exists in 4 isomeric form (A – E). A & D are the prominent ones. It is a sesquiterpene acting as pheromone also having strong insecticidal and antimicrobial properties.

(S) – (+) isomer has coriander smell having mosquito repellent property. It also acts as insecticides for flea, fruit-fly, cockroaches and codling moth. (R) – (-) isomer has smell of Lavender and sweet basil.

(R)- Isomer is more prominent than the (S)- analog. It acts as antimicrobial, pest-deterrent, local analgesic and used in making perfume. On the skin it causes heat sensation activating TRPV3 & TRPV1 receptors. Causing cool sensation in mouth by activating TRPM8 receptor also exerts tachy-cardia, vasodilation, perspiration and enhancing urination.

Exists in d (+) and l (-) isomers. It has potent insect repellent property.

It exists in α to δ isomers. A bicyclic sesquiterpene. α-isomer has sweet smell also has antimicrobial and antiinflammatory effect.

Naturally occurring sesquiterpene alkaloid that has neuroprotective property by inhibiting Acetylcholinesterase. It is a Pyridone and hetero-tricyclic compound. It is now under consideration for possible treatment of neuro-degenerative diseases especially Alzheimer’s.

It is another isomer having identical biological action acting as Acetylcholinesterase inhibitor. It could be helpful also to treat various neurodegenerative diseases.

It is tropoloisoquinoline alkaloid isolated from the rhizome of Acorus calamus. It exhibits significantly inhibitory activity against Aβ_{25 – 35} induced neuronal (PC12) cell death.

It helps improve cholinergic function and lowers the generation of inflammatory cytokines. It also blocks cholinesterase action also β-amyloid aggregation. Additionally, it exerts anti-hyperglycemic effect.

It is a saponin. It reduces osteoblast dysfunction due to the oxidative injury. It also enhances neuronal differentiation and induces type-1 collagen expression. It inhibits any spontaneous contraction of intestinal smooth muscle thus effective against diarrhea.

It offers significant neuroprotective effect against Aβ_{(25 – 35)} peptide induced apoptosis in neuronal PC12 cells. Further it helps improve cognitive deficits provoked by injecting Aβ_{(25 – 35)} peptide in mice. It is now considered to use for treating Alzheimer’s disease.

Large beneficial effects on various nervous disorders: 1) Powerful anti-epileptic behavior enhancing the level of GABA; 2) prevents Alzheimer’s disease by protecting hippocampal cells; 3) Prevents Parkinson’s disorder by enhancing the dopamine level within striatum; 4) Anxiolytic effect; 5) antidepressant; 6) Anti-ischemic effect in brain injury; 7) Prevents / cures vascular dementia by enhancing Acetylcholine level in brain / CNS neuron.

Pharmacological effects: Numerous studies on AC indicate that the plant exerts versatile bioactivities due to the presence of large reserve of different types of phytochemicals. Several important effects are briefly discussed below.

Anti-inflammatory and immunosuppressive effect – Both in vivo and in vitro studies confirmed that the ethanolic extract of AC rhizomes and leaves have strong immunomodulatory and antiinflammatory role. It inhibits the proliferation of mitogen and antigen activated human peripheral blood mononuclear cells. Its antiinflammatory action is due to inhibition of IL-8 and IL-6 also reduction of NF- κβ. Further investigation reveals that the extract prevents the generation of several pro-inflammatory cytokines via multiple pathways. On that perspective AC is obviously a novel anti-inflammatory agent. It is also noticed that the extract can reduce the neuropathic pain in laboratory animals. The effect could be due to multiple actions of antiinflammatory, anti-oxidative and neuroprotective agents in AC.

Antimicrobial and antifungal effect – Both leaves and rhizomes extract display antifungal and antimicrobial activity but it is ineffective in the case of E coli.  The identifiable compounds are α – and β- Asarone. It can also act as anthelmintic agent. Further, AC synthesizes the enzyme, Heme peroxidase which also takes part during antifungal defense. The enzyme has significant role against the growth of number of phyto-pathogens.

Antimalarial activity – AC extract has potent antimalarial role when tested against Plasmodium falciparum (3D7 strain). The identifiable component is β –Asarone. Structure factor relationship shows that 2, 4, 5 –tri-methoxy groups on phenyl ring exerts the major reactivity.

Antidiabetic effect – The extract of AC shows considerable effect. The hypoglycemic action is due to the release of insulin and subsequent inhibition of α- glycosidase. The anti-diabetic study shows that oral administration of the extract can restore the plasma glucose level in Streptozotocin induced diabetic animals. The experiment further indicates that after three weeks of treatment the level of LDL, lipid and Glucose 6 – phosphatase, fructose 1, 6 – phosphatase and other marker enzymes considerably go down in diabetic induced animals. Despite the fact that some of the phyto-chemicals within AC have hypoglycemic effect but no exact component(s) is not identified yet.

Neuroprotective effect and Alzheimer’s disease – It has been documented that AC extract provides protective effect by preventing the neuronal damage. The extract helps restore the cognitive function in brain injury sufferers. One of the identifiable compounds is β- Asarone. Using animal model, it is established that β-Asarone can prevent or reduce the Aβ (1-42 peptide) induced neuronal damage within hippocampus [Alzheimer’s animal model] of rat by down regulating BcL-2, BcL-w, Caspase-3 activation and c-jun N-terminal kinase (JNK) phosphorylation. The in vitro experiment using Aβ peptide injected cultured neuronal cells also supports the fact.

The generation of free radicals is basically the underlying reasons behind many neurodegenerative diseases and cognitive impairments. The root or rhizome extract is used in the treatment for a long period of time. The major active principle(s) has been identified later to be α – and β – Asarone. Both work by blocking the NMDA receptor channel. α– isomer is seen more potent to inhibit the binding of [H³] – MK-801 to NMDA receptor, which could be consistent with its neuroprotective role. Studies also confirmed that both α- and β – isomers enable to provide protection against Glutamic acid induced excitotoxicity while blocking the NMDA receptor function. Additionally, the extract causes significant improvement in neurobehavioral performances. The other experiments indicate that AC extract holding numerous constituents exerts neuroprotective effect during ischemia in brain as proven in the rat model.

Antioxidant activity – Abundant studies establish the large potential of AC regarding its antioxidant role. Laboratory experiments demonstrate that AC can inhibit Fe⁺³ induced epileptogenesis by modulating the antioxidant enzymes indicating the beneficial use of AC extract as an effective anti-epileptic agent. The extract can prevent the radiation induced DNA and cell membrane damage. In vitro experiments also confirm that the extract can inhibit the lipid peroxidation.

Adipogenic action – It has been identified that β-Asarone in AC might inhibit adipogenesis. The compound suppresses the expression of adipogenic transcription factors. In vitro works also show that AC extract inhibits adipogenesis and subsequently stimulates the lipolysis in 3T3-L1 adipocyte cell line. Additionally, Asarone can lower intracellular triglyceride level while stimulating phosphorylation of hormone sensitive lipase that triggers the lipolysis in adipocytes. Considering the overall aspects, AC extract shows potential in treating type-2 diabetes.

Blood pressure lowering effect – The extract of AC shows blood pressure lowering effect including the vascular modulator ability. Experiments indicate the involvement of several constituents in AC following different pathways. Among them relaxant effect is mediated via the Ca⁺² antagonism plus NO pathways causing the reduction of blood pressure whereas the vasodilatory effect is caused by different manner. So, AC is established to be antihypertensive, circulatory stimulant and vascular modulator.

 

Chamomile

General features: It is a small attractive flowering plant belonging to daisy / Asteraceae family, widely known from the very ancient time particularly throughout Europe for making herbal infusions as drinks / beverages and for traditional / folk medicines. It has slight sweet but astringent taste that also varies with the species. The herb exists in many different forms. Among them, two are the most common, German and Roman chamomile. Historically, they are famous for inducing the calming behavior, anti-inflammtory or healing effects including few other benficial health activities. The plant is native of both Western and Easteren Europe including Morocco, Greece, Turkey and places around mediterranean regions. Two major varieties are commonly cultivated, Roman (Chamaemeulam nobile) and German (Matricaria chamomilla). The former is perennial whereas the later is annual. The Roman species is somewhat shorter in size by length and so is the flowers. But German chamomile has larger sized flowers and the plant reaches to the height of about 3 ft. Besides the beverages and medicinal uses, it is also employed for the aromatherapy. The chamomile blossoms were known from the time of Pharoh in Egypt. Concerning the children story, the herb has been mentioned in the tale of Peter Rabbit when his mother sent the naughty bunny to bed by inducing sleep with a cup of chamomile tea after his bad escape from McGregor’s garden. The Roman variety has slight bitter taste thus often used in making beer instead of using hops. It grows in Central Europe and North America. German chamomile has somewhat sweeter taste and can be cultivated in verstaile climate condition even in various temperate zone like India, South Africa and Australia. It has the wild character and grows in the wilderness even in the roadside. But in recent days, chamomili flowers are carefully cultivated for commercial purposes and more than 90 % are destined for making the herbal tea after drying up the flowers and buds. The German variety in addition to its sweeter taste, also bears fruity smell of apple and quince. The Roman flowers have strong pungent and heavy spicy flavor. Considering the overall aspects, all the varities of chamomile flowers are characteristically small, white corollas and having yellow centers appearing as mini daisies.  On the average, the plant is about 6 to 24 inches tall depending on its types and flowers grow at the end of thin stems. Normally, the flowers and buds are harvested for drying to prepare tea when the flowers reach to full bloom which takes about two months at best.

History: Chamomile originates from the Greek word “Chamomaela” meaning “ground apple” for its apple like pleasant and refreshing scent. Spaniards used to call it “Mantazilla” describing it as “little apple”. The herb has a long history that covers numerous cultures and countries. Everywhere it has been used for the same reasons either for frgrances due to its sweet aroma or for its medicinal role as relaxant. In ancient time Egyptians used to offer chamomile to Gods to prevent or cure from the fever. Romans sipped the tea preapared from it as a healing drink. The oil extracted from chamomile flowers are used by the Romans for fragrance and essence. Afterward, Spaniards used it to flavor the sherry. English used to use it as a bittering agent to brew the beers. In later period it has been replaced by hops. Around the Middle ages monks utilized it as a herbal medicine in addition to brew the beer. They also observed that planting chamomile near any ailing plants would help recover from the diseases. It was recognized afterward that the scent of chamomile flower  can repel the insects and pests subsequently protecting both itself and the nearby plants.

Folk uses: For centuries, chamomile tea acts as a sleep aid also treating fevers, stomach problems, cough and cold and any inflammation. The herb can be used both externally and internally. It can be further used to treat eczema, wounds, ulcers, gout, skin irritations, scitica, rheumatic pain, burns, bruises, neuralgia, hemorrohoids, mastitis, canker sores. In some places it is even used to treat diaper rashes, cracked nipples, chicken pox, ear and eye infections, conjunctivitis, inflammation and poison-ivy. Recent studies confirms the mechanisms behind those pharamcological effects like atispasmodic, antipyretic, antipeptic, antibacterial, antifungal and antiallergic actions. It can treat gastrointestinal problems like diarrhea, indigestion, anorexia, nausea, motion sickness and colic pain among the children. It is a good emanogogue and utreine tonic for the women. Chamomile is effective against arthritis too. It is included in the pahrmacopia of 26 countries around the world.

Chamomile for drinks: Normally dry powders of chamomile flowers are used to prepare the chamomile tea. When dipped or boiled in hot water for a reasonable period of time several chemical / medicinal contents are extracted out in the aqueous medium which is considered as chamomile tea. It has nice fragrance and enable to provide soothing or calming effect on the body. The aqueous extract lacks many of the organic ingredients owing to their insolublity in the medium particularly in the case of apigenin in free condition but more as apigenin-7-O-glucoside. For making tea, German chamomile is commonly used due to its sweet flavor and fragrance. The 50 % water-alcohol extract of German chamomile after further diluting with water is often recommended to cure diarrhea. The tea is also used as mouth wash to cure inflammation inside the mouth or throat after gargling. The Roman chamomile is still being used to brew beers replacing hops due to its slight bitter taste. The essential oil extracted from flowers by various solvents are used for medicinal or cosmetic purposes.

Important Chemical constituents and some of their physiological properties: The chamomile flowers possess approximately 0.4 – 2 % (v/w) essential oil. Approximately 52 components have been identified. The highest among them are β – farnesene (~ 29.8 %), α – farnesene (9.3 %), Germacrene D(6.2 %) and Spiroether (5.6 %), (-)-α-bisabolol (~ 50 %) and chamazulene (1 -15 %). One of the major components of essential oil from Roman chamomile is n-butyl angelate and isoamylangelate. It also has other bitter sesquiterpne like Nobilin and its associated derivatives. Chamomile contains high level of flavonoids eg, quercitin, Luteolin, Patuletin and Apigenein. The fowers also synthesize monocyclic terpene like Pinenes. In addition they produce coumarin and its derivatives. The flower head particualrly produces several bitter sesquiterpenes and lactone like Nobilin. The level of contents often vary according to origins and age of the flowers. Each individual component has its own pharmacological role. Farnesene is a naturally occurring sesquiterpene possessing sweet apple odor also the smell of gardenia. It acts as a pheromone for insects whereas β – farnesene behaves as insect repellent. Chamazulene is an aromatic compound biosynthesized from matricin which is a sesquiterpene found also in the chamomile. Chamuzulene shows antiinflammatory property by acting as an inhibitor of Lekotriene B₄ generation. It also inhibits the ROS while acting as potent antioxidant. The compound has good smell and acts as migraine pain relief. Germacrene, it exists in several isomers. It is also sesquiterpene acting as a pheromone particularly to the tobacco moth. Germacrene D is an antibacterial agent also has potent cytotoxic role on human breast tumor (H_s578T) and androgen independent prostate cancer cells (PC-3). Spiroether, itinhibits the production of Aflatoxin G and in overall aspect it is a potent antifungal compound. Biasbolol both isomers α (+) amd α (-) have sweet smell. In addition they have anti-irritant, antiinflammatory and antimicrobial activities. The α – isomer is more abundant than the other one. Apigenin, it is a flavonoid having numerous biological properties particularly known for inducing autophagy (recycling of cellular waste). It is a good inhibitor of enzyme CYP2C9, needed for drug metabolism. In that way, it helps improve the problem of drug resistance. The compound can prevent renal dmages. It also acts as an activator of monoamine transporter system. Additionally, it is a waek ligand of central benzodiazepine receptor thus enables to exert anxiolytic abd sedative effect. Further it is an antagonist to NMDA receptors also can interact with the µ, δ and κ opiate receptors. Apigenin inhibits COX-2 and activate PPAR – γ providing antiinflammatory and affecting cannabinoid system subsequently modulating analgesic effect. Nobilin is sesquiterpene lactone. It acts as antioxidant and antiinflammatory agent. It also shows strong antiprotozoal activity. In addition, it has powerful anti-neoplastic behavior by suppressing the Myb-dependent gene expression since deregulation of c-Myb is known to involve in the development of human tumors especially in the case of certain categories of leukemia, breast and colon cancers. The suppression behavior and subsequent anticancer effect is not due to the implementation of usual cytotoxicity or any nonspecific cell damage. This action follows a specific path while blocking the c-Myb dependent gene expression during cell proliferation and differentiation. Besides Apigenin, chamomile synthesizes various other flavonoids like Luteolin, Quercitin and Patuletin. As usual they are widely known for their powerful antioxidant effect along with numerous other beneficial activities like antiinflammatory, anti-neoplastic, anti-diabetic also preventing from various cardivascular diseases.The esters of angelic acid like n-butyl angelate and isoamylangelate offers pleasant smell combining fruits, rose with a touch of spices. Those comounds exhibits spasmolytic, sedative and pain relieving role. Its hydrolysis releases angelic acid which can work against nervousness, appetite loss, fever, gout and headache. The presence of coumarins in chamomile acts as anticoagulant preventing any blood clotting. The presence of Pinenes offer good smell also act as strong insect repellent. Matricin is another sesquiterpene that has potent antiinflammatory action like Chamazulene. Matricin can easily convert to chamazulene. But unlike chamazulene it follows different path to block inflammation. In vitro studies using human endothelial cells (HMEC-1) indicate that Matricin inhibits ICAM-1(Intracellular adhesion molecule -1) gene expression induced either TNF – α or LPS but not by IFN – γ. Actually the level of ICAM-1 gene expression is sought to be a marker for NF-κβ activation, one of the signaling molecules involved in the inflammatory path. The compound does not express any cytotoxicity.

Some of the major ingredients of Chamomile

Pharmacological actions: Chamomile flowers display a vast number of pharmacological activities. A few of the important ones are discussed below.

Anti-inflammatory effect: The presence of ingredients like α – bisabolol, α – bisabolol oxide A & B, Matricin, Chamazulene and a large reserve of flavonoids in essential oil exerts powerful antiinflammatory effect. Human studies indicate that chamomile oil enables to penetrate quickly through the skin reaching to the deeper layer thus helping wield its topical antiinflammatory action. Additionally, animal experiments show that the oil can inhibit the release of PGE₂ when inflammation has been induced by the LPS (Lipo-polysaccharides). The decrease of Cyclooxygenase -2 (COX-2) enzyme was very noticeable without interfering the COX-1.

Anti-anxiety, anti-seizure & sedative effect: Chamomile tea and aromatherapy using essential oil has been in use for a long time for inducing sedative / tranquilizing or calming effect. German chamomile is claimed to offer major anxiolytic action. The laboratory experiments on animals suffering from seizure and convulsions generated by picrotoxin can be significantly reduced by the essential oil of chamomile. The compound, Apigenin is identified to be the underlying cause. Chamomile tea offers anti-convulsant and CNS depression effects. Drinking chamomile tea is known to induce sleep also inhaling vapor of its oil produces hypnotic action reducing stress and also helps alleviate the stress induced adrenocorticitrophic hormone (ACTH) level in plasma. Coadministration of vapor from oil along with Benzodiazepam synergizes that lowering result. It is further noticed that chamomile extract interacts with the benzodiazepam binding sites of GABA receptors of brain and CNS tissues producing the anxiolytic action subsequently preventing seizure and offering sedative effect. Besides apigenin there are few other compounds which are responsible for those effects by interacting with the GABA receptors.

Anti-cancer effect: Studies on preclinical model have shown positive responses regarding the growth inhibitory role of chamomile extract particularly on prostate, breast, ovarian and skin cancers. The studies further indicate that the extract has minimal inhibitory role on normal cells contrary to the tumor or cancer cells. The extract exerts apoptosis mainly on the cancer cells. The involvement of apigenin is largely identified although similar flavonoids and others are also included in the act. Chamomile shows good safety record as an anticancer regimen when tested on prostate cancer cell line (PC-3) both in vitro and in vivo.

Cardiovascular effect: Chamomile flowers are loaded with various flavonoids. It has been widely established that regular consumption of flavonoid enriched food lowers the risk of cardivascular diseases significantly within the adult persons particularly for the ages ranging from 65 – 84 years old. Flavonoid intake is seen inversely proportional to the mortality from coronary heart diseases. There is also an inverse relation concerning the incidences of myocardial infarction. Interestingly, among the patients undergoing the cardiac catherization, taking chamomile tea before hand enhances the brachial aretery pressure. This is a significant hemodynamic changes of flow noticed  which could be also beneficial to protect from cardiac problems.

Effect on osteoporosis: Osteoporosis creates low bone mass owing to the excessive bone resorption. It is a metabolic disorder and the patients are prone to incessant fractures of bones. The problem also rises with increase in age. In recent days, the disease is often treated with selective estrogen modulators (SERMs) which are normally bi-phosphonates or Calcitonin. The consumption of chamomile extract shows the ability to differentiate and mineralize the osteoblasts. It produces anti-estrogenic effect while stimulating the osteoblast cell differentiation possibly due to their antiestrogenic role indicating its action via the estrogen receptor.

Anti-diabetic effect: The antidiabetic action of chamomile extract is independent of insulin secretion. Numerous studies indicate that  chamomile lowers hyperglycemia by suppreessing blood glucose while increasing glycogen storage. It also has protective effect on pancreatic β – cells by diminishing hyperglycemia related oxidative stress.

Miscellaneous effects: In addition to the above pharmacological effects chamomile is also beneficial to the following health disorders:

1. Colic pain for the children.
2. Diarrhea
3. Eczema – Chamomile cream shows superiority over 0.5 % hydrocortisone.
4. Hemorrhoids – Chamomile cream helps reduce inflammation created during hemorrhoids.
5. Gastrointestinal problems – Chamomile extract has anti-ulcerative role while reducing acid output, increasing mucin secretion, decreasing leukotriene level. It also reduces spasm, flatulence and other gastrointestinal irritations.

 

 

‘Fourteen Vegetable Greens’ / Choddoshak / চোদ্দো শাক।

Note: Each member belonging to ‘Choddoshak’ family has been already discussed separately and individually in previous sections of this blog including their major phyto-chemical contents, liable for inducing versatile physiological and pharmacological effects. The members are shown below.

ওল।

 

কেঁউ / কেতকী

বেতো।

কালকাসুন্দে।

Azadirachta indica

নিম।

জয়ন্তী।

শালিঞ্চে।

Brassica campestris

সরিষা।

গুড়ুচি।

পটল / পলতা।

শেলুকা।

হিলমেচিকা।

ঘেঁটু।

শুষনী।

Members of ‘Choddoshak’: The members of ‘Fourteen vegetable greens’ / ‘Choddoshak’ and their names are provided below. Uniquely, each one of them originates from the different family which is shown along with Indian names in Bengali script. The authentic names of ‘Choddoshak’ have been collected from the renowned folk medicinal book, “Chironjib Bonousodhi” written by the most celebrated Indian apothecary, botanist and scientist Mr Shibkali Bhattacharya of Calcutta.

1) Amorphophallus campanulatus (O`l, ওল – Araceae family).

 2) Costus speciosus (Keu, কেঁউ – Costaceae family).

3) Chenopodium album (Betho, বেতো – Chenopodiaceae family).

4) Cassia sophera (Kolkasundi, কালকাসুন্দে – Caesalpiniaceae family)

5) Azadirachta Indica (Neem, নিম – Meliaceae family)

6) Sesbania sesban (Jayanti, জয়ন্তী – Fabaceae family)

7) Alternanthera sessilis (Shalinche, শালিঞ্চে – Amaranthaceae family)

8) Brassica campestris (Sorisha, সরিষা – Cruceferae – family)

9) Tinospora cordifolia (Guduchi, গুড়ুচি – Menispermaceae family)

10) Tricosanthes dioica (Patol pata, পটল পাতা – Cucurbitacea family)

11) Cordia dichotoma (Sheluka, শেলুকা – Boraginaceae family)

12) Enhydra fluctuans (Hilmechika, হিলমেচিকা – Asteracea family)

13) Clerodendrum infortunatum (Ghentu / Vontaki, ঘেঁটু – Verbenaceae family)

14) Marsilea quadrifolia (Shusni, শুষনী – Marsilacea family)

Historical and ethnological aspects: As per Indian tradition, it is customary to consume fourteen vegetable greens / ‘Choddoshak’ all at a time after frying in oil on the day before Diwali / Lighting festival. The ancient myth advocates the practice believing to keep away the demons attacking humans. Judging rationally and from logical perspectives, the demons presumably allude to various ailments intruding normal health which is somewhat noticeable during the seasonal changes of autumn. The tradition to consume ‘Choddoshak’ is running very deep, from the very ancient past. It is a ritual followed by the Hindus in India. In Indian language, the word ‘Choddo’ means fourteen whereas ‘Shak’ refers to leafy vegetables. Diwali / Lighting festival is celebrated by the Hindus all over India and considered being the largest in the nation. The date or timing falls in the autumn period. Consuming ‘Choddoshak’ before the day of Diwali is by far a strict ritualistic norm to any north Indian Hindus. The reason remains still undetermined. According to the myth, it is a belief that consuming the entire collection would take away the future chance of any attacks from the diseases during seasonal changes of autumn. The varying opinion of scholars further indicates that consuming ‘Choddoshak’ is actually mandated throughout the autumnal period or even further, not just a day before Diwali. Certainly, it provides synergistic biochemical actions to maintain a healthy body. Although a conjecture, but it is somehow viewed that intake of ‘Choddoshak’ at this time of the year helps alleviate several common seasonal diseases or disorders. Additionally, it is a millennia old practice which was once prescribed by the then ancient Indian apothecaries. The great epochal Hindu medicinal encyclopedia “Charaka Samhita” commands to consume those edible greens at autumn to keep away “Yama” the God of death. In later period, Hindu scholars clarified the real meaning of it while pointing to the fact that in tropical India, in post monsoon season and at the starting of winter most inhabitants of the subcontinent become prone to the attack of seasonal ailments. So, consuming those leafy greens would help holding strength and removing away any of the harmful possibilities concerning health. It could be perhaps a reason why the practice has been advised to continue until the next monsoon. Uniquely, the monsoon period has been intentionally deducted from round the year loop. The logic suggests that collection of clean herbs during the monsoon season obviously would face enormous difficulties since majority of the members of ‘Choddoshak’ family are grown in the low-lying areas therefore being possibly submerged under the muddy water. So there is really chance of infestation by insects and parasites as well.  It is a good reason why the bundle of ‘Choddoshak’ is introduced at an auspicious moment, the day before annual Diwali festival; the biggest celebration arrives at the end of monsoon season. In everyday life finding those invaluable herbal components is a real challenging task. Thus, in order to keep the ritualistic norm allied with quasi religiousness also combined with the ancient myth, ‘Choddoshak’ is consumed at the providential moment, prior to Diwali day.

Ethnopharmacology: At the onset of autumn in India during the month of October and November, the climate experiences sharp changes concerning temperature and humidity of the atmosphere. This climatic variation often brings numerous maladies even to a healthy human. Those ailments usually include upper respiratory tract infection, gastrointestinal problems, skin rashes, viral fever and some others.

Seasonal upper respiratory tract infection, rhinitis, allergies, cold and fever – It is believed to be a possibility that among the bundle of ‘Choddoshak’ at least three of them, Cassia sophera, Sesbania sesban and Clerodendrum infortunatum could be useful to treat those seasonal problems like bronchitis, asthma, allergy and fever due to the nature of their chemical contents.

Seasonal gastrointestinal problems – A few of the members belonging to ‘Choddoshak’ family have beneficial role to prevent or alleviate the different kind of gastrointestinal problems. Chenopodium album plays strong hepatoprotective role. The seeds and leaves of Brassica campestris / mustard (সরিষা) help maintain normal bowl movement. It also has the potent antidiuretic property. Similar way leaves of Enhydra fluctuans (হিলমেচিকা) are useful to protect from any sudden liver disorders. The other member is the leaves and fruits of Tricosanthes dioica. Its widely popular fruit, named as Patol or pointed gourd (পটোল) is also beneficial for the health. Another interesting one is either the leaves or tuber of Amorphophallus campanulatus (Elephant foot yam) which is known as O`l (ওলশাক, ওল) in Bengali that provides large help to the hemorrhoid sufferers wing to its high fiber content. In Sanskrit it is therefore called Arsogna meaning the destroyer of Arsa, hemorrhoid.

Seasonal depression disorder: Those symptoms usually occur due to the seasonal changes of weather creating sudden dryness or less humidity. The condition brings mood swings and behavioral changes including abnormal food intake, either high or low, also often accompanied with insomnia and lethargy. There is even occasional involvement of headache and dizziness. The herb, Alternanthera sessilis (শালিঞ্চে) can provide relief from the dizziness and headache. Additionally, Marsilea quadrifolia (শুষনী) and Enhydra fluctuans (হিলমেচিকা) are very helpful while acting as nerve tonic and removing away the insomnia and any mild nervous disorders.

Seasonal infection and skin rash: Enhydra fluctuans ((হিলমেচিকা) is frequently used as folk medicine to reduce inflammation and infection of skin. Among all the members, the most widely famed anti-infection species is Azadirachta indica / Neem (নিম) which known for its tremendous beneficial role on skin allergy, antifungal or antibacterial and antiviral effects. On the other hand Chenopodium album (ঘেঁটু) offers antiseptic effect and additionally Tinospora cordifolia (গুড়ুচি) acts as powerful immune modulator helping boost the overall immune system.

Pharmacological effects: It is certain that each members of ‘Choddoshak’ family enable to exert versatile physiological and pharmacological effects owing to their large reserve of biochemical contents which are immensely diverse by the nature. Below are the few activities which are often noticeable due to their pharmacological effects.

Antihistaminic, analgesic and antiinflammatory effect – It is noticed that individual leaf-extract of some of the members is potent to exert those beneficial actions when tested by using the laboratory animal models. The existence of huge stockpile of antioxidants in most of them could be one of the reasons in this regard. The inhibitory actions of flavonoids on pain perception are well documented. Essentially, the symptom occurs owing to the generation of inflammatory mediators. In addition, some flavonoids are capable to enhance Serotonin (5-HT) level within the CNS that in turn interacts with the receptors like 5-HT_2A and 5-HT₃ exerting central analgesia. In a similar manner, the antiinflammatory effect arises due to the prevention or lowering of PGE2, Leukotrienes, Substance P, Bradykinin, histamine and serotonin productions. Those mediators are also largely responsible for the asthma attack. In general, blocking those mediators provide large beneficial effects. In that regard, components like Piperidine alkaloids and particularly the flavonoid, Rhamnetin and various phyto-steroids enact strong antihistamine behavior including the broncho-dilatory effect.

Antimicrobial and anthelmintic effect – Actually, majority of the members of ‘Choddoshak’ family have the antimicrobial and antibacterial activities to a certain extent. Those synthesize alkaloids and anthraquinone compounds like Cassia sophera, Tinospora cordifolia, Costus speciosus, Chenopodium album, and Chordia dichotoma could be more potent. In addition several steroids and triterpenes are identified to be highly efficient. Many of them also have herbicidal, antifungal and antiprotozoal actions. The anthelmintic action is more pronounced in the case of Costus speciosus and Enhydra fluctuans. The later possesses a bioactive alkaloid Albendazole which works by binding to the Colchicine site of β – tubulin thus inhibiting the formation of spindle fiber essential for cell division thus causing dysfunction of the parasites.

Hepatoprotective effect – A large majority of the members offer strong hepatoprotective actions when conducted on experimental animals suffering from either by liver injury or treatment with CCl₄ which are also verified histo-pathologically. The administration of leaf extract brings back AST, ALT and ALP and bilirubin to the normal level. The identifiable components are abundant level of flavonoids, phyto-sterols, terpenes along with the others displaying the effective role.

Psycho-pharmacogical, anticonvulsant and anxiolytic effect – Studies indicate that Marsilea quadrifolia has stronger effects regarding psychopharmacological activities on behavioral aspects particularly in the case of exploratory performances. The herb also acts as a muscle relaxant and sedative. Additionally, it enables to enhance the phenobarbitone induced sleeping time. The presence of Marseligenin, a pentacyclic triterpene is thought to be the underlying cause that interacts with the Serotonin, 5-HT_2A and Benzodiazepene receptors displaying the effects. Regarding the cognitive function and learning behavior, it has been noticed that it provides beneficial effect to the learning problem sufferers and memory disordered persons. The particular cause is due to the enhancement of Acetylcholine level within frontal cortex via the inhibition of Acetylcholine esterase. The inhibition of acetylcholine esterase and subsequent elevation of Acetylcholine level within the hippocampus also helps recover from amnesia which is verified by the laboratory experiments on amnesic animals induced either by using scopolamine or electroconvulsive shock. The effective compound identified is Marsiline. Further the herb Enhydra fluctuans reduces the CNS depression also providing neural protections.

Immuno-modulatory effect – The prominent immunomodulatory role within the members of ‘Choddoshak’ family is displayed by Tinospora cordifolia (TC) and Chenopodium album. But TC also shows some cytotoxic actions. The identifiable compounds are: Syringin, Magnoflorine, N-methyl pyrrolidone, N-formyl annonain, Cordiofoliside A and Tinocordiside. Further TC displays osteoblast production thus relieving arthritis problems. It also enhances humoral immune response.

Terminalia Arjuna / Arjuna Myrobalan / অর্জুন গাছ।

General features and mythology: The plant belongs to Combretaceae family. The botanical name is Terminalia Arjuna / Arjuna Myrobalan. In Bengal, it is named as Arjun / অর্জুন, (the great warrior of Hindu epic, Mahabharata). Over the years as a valuable source of folk medicine, the plant has maintained its legendary reputation to cure any cardiac ailments. It has been proven in recent years that the major parts of Arjuna produces treasurable organic chemicals that exhibit incredibly beneficial role on cardiac health. Arjuna is a large evergreen deciduous tree that rises to the height of 60 – 85 ft spreading spacious trunks appearing to be wide canopy at the top with lowered branches. The leaves are conical oblong shaped with deep green at the upper face whereas faded green underneath. The bark is smooth grey and the flowers are pale yellow color that blooms between March and June. The glabrous and fibrous fruits are uniquely shaped dividing into five wings, 1- 2 inches in length that grow mostly between September and November.  The plant is common in India particularly in the Eastern region. It grows mostly on the banks of rivers and canals. In some regions of India, it is considered to be a sacred tree and that reputation spreads with the passage of time; possibly owned out of deep respect for its bountiful medicinal values.  In frequent occasions, the leaves and flowers are ritually offered to Lord Vishnu (the creator of universe) or Ganapati (the elephant faced God symbolizing success) in religious ceremonies. The ancient Vedic scholar Agastya (~ 1200 B.C.) mentioned many of its beneficial actions. The other eminent pharmacologist in later years, Vaghbhata, belonging to the band of writers of future chapters of Ayurveda, prescribed Arjuna bark to treat heart diseases around 7^th century, which has been cited in his famous manuscript, Ashtnagahridaysamhita; annexed later with famed ‘Charakasamhita’, the ancient Indian encyclopedia of pharmacology. The famous medic, Vaghbhata also prescribed it to treat ulcers, wounds and hemorrhages besides using for remedying the heart ailment. He also illustrated its behavioral role. For centuries the plant is renowned to cure the heart diseases thereby earning the reputed title, ‘Guardian of heart’. In the great Hindu epic, Mahabharata, the famous warrior was named ‘Arjun’ after this plant, distinctively defined for his powerful role as being the protectorate of life. After Vaghbhata, several celebrated ancient Indian medics used to prescribe various decoctions prepared from bark as a tonic and curing numerous cardiac problems. Interestingly, Vaghbhata learnt some of those facts from the Muslim scholars while staying with them in disguise. The history tells that after the Muslim invasion, the Brahmin scholars of India lost their manuscripts and records to them. Afterward in order to get it back, the Brahmin community sent Vaghbhata, an extraordinarily talented individual to learn from the Muslim medics which he performed very efficiently while staying with them in complete disguise. Returning to own community in the later period, he recorded those facts in Sanskrit with great detail within Ashtnagahridaysamhita, which has been credited in future as a part of Ayurveda also.

Ethno-pharmacological role of Terminalia species: The plant Arjuna falls within the genus of Terminalia which holds ~ 250 species. They are all essentially distributed within the tropical and subtropical regions of the globe. Majority of them carry large medicinal properties that are highly beneficial for health to prevent or cure many ailments. These facts are superbly documented within the ancient Indian encyclopedia, Ayurveda. Among the species, Terminalia Arjuna (অর্জুন), Terminalia bellirica (বহেরা) and Terminalia Chebula (হরিতকী) are the majorly used plants which were vastly employed by the Indian apothecaries at past. Apart from India, various countries in South Asia and African continent followed the similar path to treat the native population in times of need. In India, the Ayurvedic practitioners still employ numerous Terminalia species to treat various health disorders eg, cough and cold, abdominal pain, conjunctivitis, diarrhea, dysentery, fever, headache, pain, heart disorders, inflammation, sexually transmitted disease, worms, wounds, ulcers, hemorrhages and leprosy. But in the context of cardiac ailments Terminalia Arjuna stands out particularly being the most important one. Judging by the overall aspects, the unique combination of abundant naturally occurring different phyto- components of versatile characters in each one of them also subsequent innovation concerning the usefulness at past is really an intriguing factor. Below is the table showing the uses and contents of three Terminalia species.

Three widely used Terminalia species in India

 

Name	Native name	Origin	Medicinal role	Identifiable Medicinal components
Terminalia Arjuna	Arjuna	India, Sri Lanka & South East Asia	Anti-inflammatory, Analgesic, Antioxidant, Cardiac Stimulant, Antihypertensive, reduction of cholesterol & lipid.	Terpenoids, Flavonoids, Tannins, Gallic acid, sitosterol, Ellagic acid, Pro-anthocyanidins.
Terminalia Bellerica	Bahera	India, Sri Lanka & South East Asia	Expectorant, Laxative, treament of cough & Cold, Anemia, Diuretic, Anthelmintic, Antipyretic, Analgesic, Aphrodisiac & cure Alopecia.	Bellericanin, Gallic acid, Ellagic acid, Lignans, Anolignan, β-sitosterol, 7-hydroxy-3,4- (methylene Dioxy)-flavone.
Terminalia Chebula /Chebulic Myrobalan	Haritaki	India, Nepal, China, Sri Lanka, Vietnam, Malaysia	Anti-tumor, Eye problem treating cough & cold, digestive disorders, Inflammation, Anthelmintic, Aphrodisiac & Tonic	Terflavin B, Chebulinic  Acid and others.

Folk medicinal uses: The bark extract has been used to cure skin problems or healing any bruises. The extract mainly acts as a cardiac stimulus also having good tonic property. It is generally believed that the extract strengthens heart muscle and helps maintain its proper rhythm. It is found to be a good remedy for the angina sufferers also helping hypercholesterolemia. Aqueous alcoholic extract of stem bark possesses inotropic, anti-ischemic, anti-platelet, anti-atherogenic and anti-hypertrophic activities. The plant is indisputably famous for its cardio-protective role. It also induces diuresis thus helping additional reduction of the arterial blood pressure. Further it can prevent hemorrhages and kidney stone formation by allowing expulsion of small stones / calculi. It is known to be a good febrifuge. The leaf juice is a good remedy for earache, diarrhea and dysentery. Additionally, it helps fight against Syphilitic infection. Several decoction prepared from the bark is used to reduce pain, high cholesterol, stress, diabetes, nervousness, leukoderma, tumor, asthma and hypertension. Besides the medicinal uses, other interesting feature of leaves is, they are fed to the moth, Antheraea paphia that generates the famous tussar silk. Below is the list of compounds identified in Arjuna plant.

Identified phytochemicals in various parts of Arjun tree

Plant parts	Chemical categories	Chemical components
Stem bark	Triterpenoids	Arjunic acid, Arjunolic acid, Arjungenin, Terminic acid, Arjunglucosisdes, IV & V, Arjunasides A – E, 2-α, 3- β-dihydroxyurs-12, 18-dien, -28-oic acid ,28-O-β-D-glucopyranosyl ester.
	Glycosides	Arjunetin, Arjunoside I & II, Arjunapthanolside, Terminoside A,
	Flavonoids	Arjunolone, Arjunone, Baicalein, Luteolin, Gallic acid, Ethyl gallate, Quercitin, Kaempferol, Pelargonidin, Oligomeric Proanthocyanidins.
	Tannins	Arjunin, Pyrocatechols, Punicalin, Punicalagin, Terchebulin, Terflavin B, Castalagin, Casuarin, Casuarinin.
	Sterol	β-sitosterol
	Glycosides	Arjunoside I, II, III & IV, 2α-19α-dihydroxy-3-oxo-olean-12-en 28-oic acid, 28-O-β-D-glucopyranoside.
Leaves	Sterol	β-sterol
	Flavonoids
	Alkaloids
	Tannins
	Phenolic compounds
	Acid	Oxalic acid.
Fruits	Glycosides
	Flavonoids	Luteolin
Seeds	Glycosides	14,16-di-anhydrogitooxigenin-3β-D-xylopyranosyl (1-2)-O-β-D Galactopyranoside.

Chemical structure of few important tannins of the above table

Chemical structure of several triterpenes, flavonoids, phenolics, Anthocyanidin & others of the above table

Pharmacological effects:  The plant earns its incredible reputation due to multifarious beneficial actions particularly for its direct action on cardiac health which is the most widely studied subject among others. The bark syrup or powder is still in extensive use for controlling or preventing cardiovascular and other disorders by many.

Cardiovascular activity – From the ancient times, medics employed several decoctions of Arjuna to treat numerous cardiovascular ailments also to regulate the adversarial role of hyperlipidemia leading to fatal cardiac problems. It is proven that the bark extract efficiently alleviates angina disorders. The underlying cause is majorly directed toward its powerful antioxidant property. The stem bark is known to hold a large reserve of antioxidants that include flavonoids, glycosides, tannins, terpenes, sterol and several inorganic elements. Among them triterpenes produce significant effect. The phyto-compounds like, β – sitosterol, Terminic acid, Terminoside A and Arujunaphthanoloside particularly draw attention for their potent individual therapeutic actions. In laboratory experiments, Terminoside A prevents NO production by reducing the NOS level of expression in LPS stimulated macrophages. Additionally, Arujunaphthanoloside exerts strong antioxidant effect. Further, the large reserve of flavonoids (5698 ± 531 mg / 100 g) also contribute heavily in this matter. Evidences confirm that these flavonoids prevent oxidation of LDL and cholesterol by its free radical scavenging ability subsequently inhibiting endothelial activation as well as the platelet aggregation via cyclooxygenase hindering effect, in that way preventing the fatality of thrombosis. So, Arjuna bark is beneficial to control the cardiovascular diseases. The other important phyto-component of this plant is hydrolysable tannin content. Interestingly, they enable to enhance the NO synthesis which leads to relax the vascular tissues stimulated to contract by epinephrine. It creates hypotensive effect allowing an easy flow through the coronary arteries. Studies also indicate that the bark extract enhances the rate, force and amplitude of contraction causing the enhancement of cardiac output. Additional enhancement of PGE2 is also noticed affecting coronary vasodilation thereby increasing the blood flow also, and improving the cardiac cell mitochondrial uptake. In essence, the bark offers excellent protection against oxidative stress simultaneously reducing the levels of lipid peroxidation. As a further addition it raises the level of HDL in circulation. Below is a few other cardiac parameters which shows improvement by the extract of Arjuna.

Angina / Myocardial infarction – It has been noticed that the mean angina frequency is significantly decreased with simultaneous lowering of systolic blood pressure. Improvement of ECG change has been noted wit subsequent reduction of plasma cortisol and cholesterol level.

Ischemic mitral regurgitation – In double-bind randomized placebo control trial with patients having ischemic mitral regurgitation (IMR) following acute myocardial infarction, the bark extract can significantly lower the IMR as well as anginal frequency. Significant improvement in diastolic dysfunction is also noted (E/A ratio changes from 0.93 ± 0.31 to 1.38 ± 0.40 within 12 weeks).

Cardiomyopathy – Besides its anti-ischemic role the use of extract reduces left ventricular mass (LVM) while improving left ventricular ejection fraction (LVEF). Studies indicate that if patients having dilated cardiomyopathy with reduced LVEF received the extract there is considerable improvement of left ventricular parameters and its functional capacity.

Platelet aggregation – The bark extract dosedependently decreases platelet aggregation which could be one of the underlying reasons behind its antithrombotic role. The effect has been tested in vitro using twenty patients with either sex having proven coronary artery disease. Presumably, it desensitizes the platelets by interacting with the surface receptor(s) thus interfering the signal transduction.

Congestive heart failure & hypertension – In preliminary studies using human subjects, it has been noticed improvement in breathlessness, overall wellbeing and progress in diuresis accompanying with the fall in systolic and diastolic blood pressure. Studies on hypertensive subjects show improvement of cardiac function indicated by the increment of ejection fraction, significant reduction of systolic blood pressure and left ventricular internal diameter. It also helps improve cardiovascular endurance in lowering systolic blood pressure within normal healthy individuals.

Rheumatic heart disease – Patients suffering from rheumatic heart valvular disease with congestive heart failure problem were administered Arjuna extract at least three times a day shows considerable improvement in left ventricular ejection fraction (LVEF), reduction in heart size and exercise duration.

Anti-inflammatory and immunomodulatory effect – Arjuna produces versatile phyto-components that focusses on different aspects of inflammatory processes. In general, during inflammatory actions there is cellular release of varieties of biomolecules. Those are actually vasoactive components like Bradykinin, Prostaglandins and various amines. They are released along the inflammatory pathways intending to dilate the blood vessels opening the junctions between cells allowing leucocytes migration through capillaries. Compounds enable to block the vasoactive ability act as therapeutic and are categorized as anti-inflammatory agents. The anti-inflammatory effect is usually due to the inhibition of enzyme Cyclooxygenase resulting in the obstruction of Prostaglandin synthesis. Experiments further indicate the downregulation of Cyclooxygenase – 2 (COX-2) and 5-lipoxygenase (5-LOX) TNF- α and IL – 6. As a result of their downregulation, the generation of inflammatory mediators like NO or PGE2 are prevented by the components within Arjuna. For example, Chebulic acid can prevent mitogen activated protein kinases (MAPKs) that in effect control inflammatory / immune responses by the reactive oxygen species (ROS).

Antineoplastic effect – Normally, pro-oncogenes along with the tumor suppressor genes are liable for encoding the proteins which effectively regulate the cell cycle, repair of damaged DNA as well programmed cell death or apoptosis. Mutations within those genes lead to the generation of cancer. These mutations indicate that there is no need of external signals for cellular proliferation. Additionally, those cells turn unresponsive to the restrictive signals during cell division which eventually results in uncontrolled cell growth called cancers. In cancers, numerous genes are altered and transmitted into the daughter cells which avoid normal growth restraint. Components in Terminalia Arjuna are enabled to prevent cancer or its progression. For example, one of the tannins, Casuarinin from the bark extract induces apoptosis in human lung cancer cell line (A549). The enhancement of Fas / APO-1ratio as well as the increment of membrane attached Fas ligand are responsible for the apoptotic effect. This tannin also arrests the cell cycle at G₀ / G₁ phase due to p53 dependent induction of p21/WAF-1.

Wound healing action – From the ancient times, Arjuna is famously known for its wound healing role. In general physiologically, the growth of endothelial, epithelial and fibroblast cells is a necessary event for the healing of wounds. The plant, Arjuna synthesizes numerous phyto-components that enable rapidly to heal the wounds. Additionally, few components in it also possess potent anti-microbial property that assists further in the healing path. Essentially, three separate fractions are identified to lead the event. The most potent one is seemingly enriched with tannins which may logically indicate that tannins play a significant role in the overall process. Uniquely, same fraction shows the highest anti-microbial activity. Incidentally, treating the excision wound with this fraction shows highest increment of Hexosamine level (necessary extracellular matrix component) in comparison to the other fractions. In addition to the cell growth and proliferation event, healing also requires remodeling of the tissue matrix. Surprisingly, the same one with highest level of tannin is able to affect the remodeling process. The other fractions even with significant tannin contents are seen less effective which could be possibly due to the existence of considerable amount of reducing sugars that may delay the healing process. The other phenolic components also have the role in wound healing. Additionally, β – sitosterol and its glucosides, commonly found in all Terminalia genus plants promote angiogenesis and endothelial cell proliferation. It is known that reduced sterols having antioxidant property enhance the wound healing whereas its oxidized form with pro-oxidant effect induces the cell death. In that way, β – sitosterol and its glycosides have potential role in wound healing. The role of flavonoids and anthraquinones and their glycosides also exert strong proliferative effect possibly due to powerful antioxidant activities.

Antidiabetic effect – Antidiabetic activities of Arjuna are known for a long time. The extract from bark shows the highest potency compared to others. It shows inhibition toward the gluconeogenic enzymes like, Glucose – 6 – phosphatase, Fructose -1, 6 biphosphatase and stimulated Hexokinase. The experiments already have proven that tannins like Chebulagic acid, Chebulinic acid can inhibit α – glucosidase activity.

The effect of Arjuna bark extract on diabetic rats shows reduction of lipid peroxidation with simultaneous increase of antioxidant enzymes like Superoxide dismutase, Catalase, Glutathione peroxidase, Glutathione-S – transferase and Glutathione reductase along with the rise of several antioxidants eg, Glutathione, Vitamin A and E, Ascorbic acid proteins with sulfhydryl groups. The extract also stimulates insulin secretion from pancreatic β cells, comparable to Glibenclamide. It also helps enhancing the uptake of glucose mimicking Insulin.

Antidiabetic components of Arjuna plant

Hepatoprotective and renal protective action – Experiments on animals indicate that Arjuna extract provides protection to the liver and kidney from the oxidative stress exacted by toxins or drugs. Mice pretreated with the bark extract show much less reduction of cellular antioxidants than those exposed only to CCl₄ or high dose of Tylenol. Those toxic ingredients markedly decrease the level of Glutathione, Superoxide dismutase, Catalase and Glutathione – S – transferase. The pretreatment with Arjuna extract prevented from oxidative stress by scavenging the generated ROS which usually inflicts the damage within both liver and kidney. The large reserve of antioxidants within the extract and its associated scavenging ability of ROS possibly involved in the overall process.

Antifeedant / repellent activity – The bark extract has a regulatory role on Sitophilus oryzae, a pest that affects rice, maize, wheat and similar other crops. The methanol extract particularly shows greater impact on the adults. No exact component(s) is identified yet. From the food safety point of view, the extract is considered to be ideal.

Toxicity – Studies conducted after consuming 1 – 2 g per day for two years within patients particularly those having cardiovascular disease show no significant side effects like headache, gastritis or constipation etc. No adverse reports regarding hepatic, metabolic renal or hematological problem are ever cited after continuing two years of its use.

Colocasia esculenta /Elephant ear/ Taro / Malanga / কচু।

General features: The botanical name is Colocasia esculenta which is colloquially named in English as Taro, often cited as Elephant Ear. In Bengali it is called Kochu / কচু।. In Spanish, it is recognized as Malanga. It is herbaceous perennial tropical plant belonging to Araceae family. The corm or tuber is a widely known staple food of Africa, Oceania, Pacific islands and many places in South Asian nations. Its origin is somewhat unknown, but it has been believed that Taro has travelled following the trade route of ancient traders from Asia. It is the most extensively and earliest cultivated plants of the world. Although it is primarily grown to consume the starchy corm, but stem, freshly sprouted leaves and petioles are also used as vegetables for edible needs. In Bengal stretching from West to East (Bangladesh), taro or its leaves are considered to be delicacy. Innumerable tasty dishes are prepared either from the corm or stems or by the freshly sprouted leaves. It is more appealing to the Bengalis than the Elephant foot yam (O`l). Identically, it is a vegetable grown out of rhizomes of different shapes or sizes. The leaves are approximately 16 inches x 10 inches and grown from the rhizome. When fully grown, they are dark green on the upside +whereas lighter at beneath. They are triangular ovate but mucronated at the apex. The petioles are 3 – 4 ft long, thick and succulent also often purplish in the appearance. It is attached to the center of the leaf.  The spadix is about 3/5 long as spathe with flowering part ~ 0.3 inch in diameter. The female part is situated on the fertile ovaries mixed with the white colored sterile ones. The neuters grow above the female part which are irregular lobed having six to eight cells. The corm shaped like a top usually weighing ~ 2 Ibs which can be more like 8 Ibs. The plant can be almost 7 – 8 ft high with canopy spread ~ 8 ft also. There are about 200 cultivars of taro grown for the edible corms or cormels. The later ones are smaller in sizes and grown as clusters. In Bengal they are known as Kochumukhi /কচুমুখি।. The taros are categorized either as wetland or upland. The former is composed of main large corm whereas the later produces several eddoes (কচুমুখি) that can be used like the potatoes for cooking. It is certainly a good source of fiber associated with complex hardy starch. It offers many health benefits. For example, it improves cardiovascular and digestive health, controls blood glucose level and body weight. It has loads of antioxidants enabling to protect the body from free radical damage or preventing from the generation of cancers.

Historical facts of taro use:  Taro is often claimed to be the native of India. Seemingly, in later years the plant traveled to the East Asian nations like Myanmar, China, Indonesia, Malaysia and other countries including Japan by the traders or travelers. Afterward, it moved further to Hawaii, Melanesia, Micronesia and other Polynesian islands including far away to Papua New Guinea. Possibly, from there, it got entry into the Latino countries of South America also to North American nation of Mexico. History also tells that Taro has been widely spread to Africa and its neighboring Mediterranean regions. Many countries of African continent and pacific islands and Papua New Guinea use taro as a staple diet.

Nutritional benefits: Taro mostly tastes like the potatoes with a bit of added stickiness feeling. It is an excellent source of nutrients, vitamins and minerals. About 104 g (1 cup of fresh cut) taro provides ~ 72 g water, 27.5 g carbohydrate, 1.6 g protein, 0.2 g fat and 4.5 g dietary fiber. The sugar content is low, ~ 0.4 g. It is also a good source of minerals eg, Cu – 0.18 mg, Mn – 0.4 mg, Mg – 34 mg, P – 88 mg, K – 615 mg, Na – 11 mg, Zn – 0.25 mg and Se – 1 µg. Additionally, it produces large quantities of free amino acids eg, Trp – 0.03 g, Thr – 0.08 g, ILeu – 0.06 and Leu – 0.2 g and Lys – 0.1 g. Further, it is a good source of vitamins too eg, B1 (Thiamin) – 0.1 mg, B2 (Riboflavin) – 0.03 mg, B3 (Niacin) – 0.6 mg, B5 (Pantothenic acid) – 0.3 mg, B6 (Pyridoxine) – 0.3 mg, B9 (Folate) – 23 µg, C (Ascorbic acid) – 5 mg and Choline – 18 mg. Interestingly, it also synthesizes fat soluble vitamin A and E. Aside from commonly used taro tuber/ corm, the fresh stems and leaves are also the good sources of minerals and vitamins.

Major bioactive phyto-chemicals: The plant synthesizes flavonoids, β – sitosterol and steroids along with the other phyto-components. The alcoholic extract displays the presence of alkaloids, flavonoids, saponins and tannins as the major components. Corms synthesize various anthocyanidins eg, Perlargonidin 3- glucoside, Cyanidin 3 – Rhamnoside and Cyanidin 3 glucoside. The extraction by ethyl acetate plus butanol provides almost ten components displaying large varieties of flavonoid glucosides and phenolic compounds like Feruloyl glucoside or Caffeoyl glucoside.

The leaves (0.61 %) and pericarp (0.36 %) show good reserve of essential oil composed of numerous monoterpenes like Limonene, Geraniol, Bornyl acetate, Geranial / Citral, Myrcene, Sabinene, Myrtenol and Terpinen – 4 – Ol. The oil shows strong anti-microbial and fungicidal property since many of the individuals among them display the similar role. Among the ingredients, Limonene is seen being at the highest concentration.

Use of folk medicine: Taro is frequently used as village medicine to treat asthma, diarrhea, and hemorrhage and any skin problems. According to the Ayurveda, it can provide relief for the arthritis, stomatitis, alopecia and debility.  Juice made of petioles is prescribed for relieving the earache. To treat alopecia, the juice of corm is employed on the affected area. Leaf juice is known to control internal hemorrhages, adenitis (inflammation of glands) and otalgia. It works as an antidote to insect, wasp and scorpion sting also has the anthelmintic property. The heated tubers are pressed locally on the surface to reduce rheumatic pain in joints. Usually, taro helps digestive system by acting as laxative consequently good for the hemorrhoid sufferers. Uniquely, corm is claimed to have the abortifacient property and can control infections like tuberculosis, pulmonary congestion and fungal abscesses.

Health effect of taro: Besides having good tastes, the leaves and petioles are highly enriched with numerous minerals. It is noticed that leaf juice behaves as expectorant and stimulant. It has the astringent and styptic taste and in addition it also acts as rubifacient. Usually the corm, leaves and petioles in taro have raphides / calcium oxalate which commonly produces stinging sensation inside the mouth which can be easily removed by boiling in water with bicarbonate. The tubers offer digestive, laxative, diuretic, demulscent and anodyne effect. It is noticed that taro also produces analgesic, anti-inflammatory, anticancer and hypo-lipidemic effect.

Health benefits: Taro is loaded with important minerals and vitamins which has good impact on health. Below is the list of several beneficial effects.

Cancer prevention – Taro corm is full of antioxidant components like vitamin A and C including several other phenolic antioxidants including flavonoids and anthocyanidins. They enable to boost immunity while removing away hazardous free radicals generated within the body. Along with the other carotenoids, the presence of Cryptoxanthin is very noticeable since it has the proven ability to reduce the chances of lung and oral cancers. Further, in vitro studies on colon cancer cells (YYT) indicate that taro extract follows two pathways to control the cellular progression of tumors. One of them is by inducing apoptosis directly whereas the second one is by activating the lymphocytes which in turn ultimately leads to the lysis of tumor cells.

Further, the recent finding confirms that a 200 KDa polysaccharide from taro corm shows significant anti-metastatic potential when tested both in vivo and in vitro. It is made of 64 % neutral sugar and 36 % uronic acid.

Prevention of rheumatoid arthritis – The presence of vitamin B6 in corm seems able to reduce the symptoms of rheumatoid arthritis including muscle aches, joint pain or chronic inflammation of joints.

Antimicrobial and antifungal property – The extraction by CH₃OH + CHCl₃ shows strong dose-dependent antimicrobial and antifungal actions when tested by following the agar diffusion technique keeping Tetracycline as control. Almost identical behavior is noticed for aqueous extract also. Both extracts are active against gram positive and gram-negative bacteria as well as the fungal strain like Aspergillus niger and Candida albicans. The effect is possibly due to the presence of numerous monoterpenes.

Anti-hepatotoxic activity – Uniquely, the leaf juice shows anti-hepatotoxic and hepatoprotective activity when tested on liver cells or liver slices treated with either CCl₄ or Acetaminophen (Tylenol). The leakage of liver enzyme markers (AST, ALP & ALT) are evaluated in presence of absence of the leaf juice. Interestingly, the juice significantly reduces the extent of enzyme leakage within the media. Technically, treating with CCl₄ and Acetaminophen generates free radicals which causes lipid-peroxidation that leads to produce malondialdehyde creating a colored chromophore while reacting with Thiobarbutyric acid indicating the extent of free radical generation ability. The addition of leaf juice reduces the lipid-peroxidation with concomitant lowering of the color production. Besides leaves, the extract of corm also shows similar effects. In all cases presence of large level of anthocyanidins and flavonoids is suggested to be the underlying factors.

Antidiabetic effect – The ethanol extract of taro leaf causes significant reduction of blood glucose level within Alloxan induced diabetic rats. The effect is comparable to anti-diabetic medication, Metformin.

Anthelmintic effect – Both aqueous and ethanolic extract of leaf and corm show potent anthelmintic activities when tested against earthworm at 50 mg / ml which is comparable to Piperazine citrate, 10 mg / ml.

Anti-melanogenic activity – Burk of taro tuber synthesizes few lignan derivative and some of them show strong anti-melanogenic effect when tested in isolated cultured melanocytes. One of them has been identified to be monoglyceride type eg, (2`S) – 1 – O – (9 – oxo- 10 (E), 12 (E) – octadecanoyl) glycerol. This compound shows considerable anti-melanogenic effect.

Immune stimulating effect – Crude protein extract from the taro corm shows potent immunomodulatory effect on hematopoietic cells of C57BL / 6 and BALB / C mice. The extract stimulates in vitro proliferation of mice splenocytes dose-dependently in both strains. The intraperitoneal administration of extract induces splenomegaly and proliferation of spleen and bone-marrow cells as well. Further it elevates in vivo B220⁺ splenocyte proliferation with simultaneous reduction of mature (B220⁺ IgM⁺) and immature B cells in bone marrow. The generation of antibody by the B220⁺ splenocytes marks the activation of B1 cells by extract in C57BL / 6 indicates the presence of good source of immunomodulatory protein(s) in taro.

Anti-feeding activity – The anti-feeding and insecticidal effect is tasted against cotton leaf worm using petroleum ether extract of taro leaves. The major identifiable compounds are two phytosterols, β – sitosterol and stigmasterol. It has been further noticed that these sterols also provide self-defense to Colocasia esculenta / taro plants.

Amorphophallus campanulatus / Elephant foot yam / O`L / ওল।

General feature: It is a perennial tropical plant with large sized oval shaped tuber. The botanical name is Amorphophallus campanulatus (AC), colloquially called Elephant foot yam. In Bengali language, it is known as O`l / ওল।. The plant, AC grows in entire regions of South Asia, Africa and several of the Pacific Islands. It earns large popularity as vegetable. Therefore it is cultivated in many countries as cash crop particularly in some of the places of Africa. Varieties of vegetarian dishes are prepared by using plant and the tuber. The origin of AC is identified to be in India which seems later being spread to the other tropical nations around the globe eg, New Guinea, Oceania, South Australia and Madagascar. Interestingly, the Indian variety shows less genetic diversity. AC growth takes place from the soil as a flower which is best described being the ugliest one. During blooming the flower spreads foul scents that lasts only for few hours with simultaneous release of heat in the surroundings. Uniquely, the flower exists only for about five days. The heat and foul smell mimicking the rotten flesh attracts flies which helps the further pollination of flower. Elephant foot yam is aroid by nature having a flower grown out of maroon colored bulb surrounded by maroon and green blotched bract. The solitary leaf that emerges after flowering appears to be a small tree. The plant belongs to Araceae family which rises to the height of ~ 8.0 ft having the stem of 5 – 7 ft tall above the ground. Its appearance resembles to an umbrella. As per the foliage, the leaf blade is divided into numerous leaflets as a whole cluster reaching ~ 6.0 ft across. The underground tubers are oval shaped and hemispherical with ~ 1.0 ft in diameter, weighing ~ 15 – 50 Ibs covered with rough hair. In Bengal, it is popularly known as O`l / ওল, often eaten with steamed rice after boiling and smashing with added salt, oil and spices. The green leaves and stems are consumed after making hot and spicy curry. Before using, the chopped tubers, green leaves and stems are left soaked with bicarbonate water at least for overnight to remove the raphides (Calcium oxalate needles) which frequently create unpleasant stinging sensation or pain within the mouth, tongue or throat. The raphides / Ca-oxalate needles are present almost everywhere in the plant including leaves, stems and corms, but more in the later. In India, O`l / Elephant foot yam is cultivated as intercrop plant along with ginger under the coconut or banana trees. It has low rate of production thus being regarded as underutilized crop. But along with its large nutritional aspects the plant has several anti-nutritional components also. In Africa and far Asian nations, the elephant foot yam is actually consumed as staple food. Besides the use as vegetable, it is usually dried and powdered for make various food stuffs for daily use.

Health effects: It helps maintain normal bowel movement avoiding constipation, cramps and several other intestinal problems. It also claims for the ability to lower cholesterol level subsequently inducing the weight loss incident. It alleviates arterial and vein blockage also reduces sugar level among the diabetic patients, thus often recommended for the diabetic sufferers for consumption. Besides its high K, Mg, P and Ca content, it also possesses high level of Se and Zn which usually has a good impact on the memory and concentration. Further, it enables to boost immunity and acts as a detoxifier and anti-inflammatory entity. It synthesizes potent anthelmintic agent also exhibits carminative property as well. It has the ability to slow down early aging phenomena. It helps treating the diabetes, dysmenorrhea, dyspepsia, tumors, rheumatism and elephantiasis. The tuber also assists to maintain the normal hormone levels in the human.

Nutritional and antinutritional aspects: Factually, elephant foot yam tubers are the good source of minerals, but it does not provide the complete nutrition due to low protein content (~ 1.13 %) required for the daily need. In most occasions, tubers are mostly consumed rather than the leaves or stems so nutrient and antinutrient contents of tubers are the major concern for health of human, cattle and chickens particularly in those regions where it is heavily consumed as a staple food due to high starch (~ 20 %), less fat (~ 1%) and moderate fiber (~ 3 %) content. Regarding minerals, the average Phosphorous content is high ~ 1443 mg / Kg along with high level of Calcium (8536 mg / Kg) and Magnesium (1512 mg / Kg). It is known that Calcium, Magnesium and Phosphorous are important and necessary minerals for the effective physical functioning ability. The AC tuber also synthesizes several proteins. One of them is Discorin (di-peptide, 31 KDa), which has immense biological role while acting as anti-hypertensive, vaso-relaxant, antioxidant and immunomodulatory actions. It is also present in other yams with varying extent.

       The antinutrient contents are also a major focus for those consuming it as a daily staple food. The antinutrients are, oxalate, tannins and cyanides which may influence in many ways either by causing intoxication or by decreasing the mortality and food intake. One of the antinutrients is oxalate (318.5 mg / Kg) which is seen really high. It normally exists in most cultivar at low level (acceptable limit = 19 – 29 mg / Kg). Undeniably, the oxalate level is dependent on soil, climate and season too. The antinutrient action of oxalate is due to its mineral chelating ability. The hazard mainly arises due to chelating of Ca⁺² producing insoluble calcium oxalate that creates the calcium malabsorption causing hypocalcemia. Besides instigating hypocalcemia to occur, the deposition of Calcium oxalate crystals inside the kidney eventually creates painful kidney stone leading to hematuria.  Uniquely, cattle and sheep become less affected since they enable to degrade the oxalate within intestinal lumen to a certain extent whereas the humans cannot (~ less than 40 mg in total). Either drying under the sun (endogenous enzyme degradation) or washing away by bicarbonate solution (0.1 %) would considerably reduce the oxalate load bringing the level to the edible range. The other antinutrient factor is tannins which is also fairly high (~ 0.46 %) in the elephant foot yam. Being a complex phyto-polyphenols, tannins can trap the metal ions, large macromolecules like proteins and polysaccharides. Tannins usually have high affinity toward the proteins. They are essentially responsible for reducing the food intake. Its high consumption (~ 120 gm / Kg) also inhibit the fiber degrading bacteria within intestine exerting lowering of growth rate. In case of chickens the effect reduces egg production quite significantly.

The next objectionable entity in elephant foot yam is Hydrogen cyanide (HCN) (~ 36 ppm). It is actually synthesized throughout the plant kingdom to a negligible extent existing mostly in glucosides form. It is seen superbly high in Cassava root (350 – 1000 ppm) also depending on the sources. Cyanide is toxic to all living matters due to inhibiting role on Cytochrome oxidase which is integral part of cellular respiratory system. If inhibited then cells will undergo rapid ATP deprivation bringing gasping, convulsion, paralysis and subsequent death. Cyanogens can be removed by drying, soaking or fermentation procedures.

The other antinutrient factor is high level of Phytic acid (165 %) because of its severe chelating ability with the metal ions that lowers their absorption through the small intestine thereby affecting numerous metabolic processes. About 5 – 9 mg /100 g Phytate in food generally lowers the iron absorption ~ 5-fold. Just by cooking at high temperature (> 91^◦C) or prolong drying under the sun, the phytate level in food can be lowered to ~ 51 %. The recommended level of Phytate in any food is ~ 25 mg / 100g. The value is somewhat higher than the level presents in most of the elephant foot yams.

Folk medicinal use: The entire plant is known for its beneficial use in Indian folk medicine. It was recommended in the ancient Ayurveda and Unani branches of medicine. The bulb is prescribed for asthma, bronchitis, abdominal pain, spleen enlargement, dysentery, emesis, hemorrhoid and elephantiasis and rheumatic problems. Recent pharmacological studies indicate that it has numerous ingredients which exerts varieties of physiological effects including analgesic and cytotoxic activities. Interestingly, when administered along with the antibodies it potentiates the anti-bacterial role.

Phyto-chemicals: Identification of phytochemicals in elephant foot yam reveals the presence of alkaloids, tannins, carbohydrate, flavonoids, phenolics, saponins and steroids. The aqueous alcoholic extract displays more components than other ways of extraction. Although the existence of alkaloid has been noticed but no exact structural identification has been made yet. Below is some of the important bioactive phyto-components.

It is a diterpenoid isolated from the elephant yam that has major biological effects while acting as anti-bacterial (better for gram + ve than gram – ve), antifungal and cytotoxic effects. In nature it exists as racemic (±) mixture.

It is a flavonoid that has strong antioxidant role and antibacterial property covering both gram + ve and gram – ve types.

Ambylone is a triterpene which has strong antibacterial, antifungal and cytotoxic behavior.

1, 3, 5-benzenetriol is a trihydroxy phenol. It acts as an anti-spasmodic drug used for the bowl pain particularly for the patients having irritable bowel syndrome (IBS) or gall stones and other GI problems.

These are the widely known phyto-sterols which have beneficial effects in human. The reports indicate that it can lower blood cholesterol (~ 15 %) along with LDL level (~ 10 %) in circulation thus reducing the risk of cardiovascular diseases. It also has positive impact by acting as anti-inflammatory also preventing the possibility of BPH or prostate cancer.

Those fatty acids belonging to unsaturated and saturated categories have both good and bad effect physiologically. Oleic can lower LDL simultaneously enhancing the HDL level. Linoleic acid is perhaps the most useful unsaturated fatty acid in physiology. It is a necessary ingredient to produce Prostaglandins, Leukotrienes and Thromboxanes. Those are important ingredients for maintaining and protecting normal health.  Myristic acid helps maintain the lipid bilayer on cell surface. Palmitic acid although intends to increase the level of LDL but it assists to produce Retinoyl palmitate subsequently generating Vitamin – A. Elephant foot yam also produces several vitamins. The major one is Vitamin E which is an essential component for health.

Several important phytochemicals in Amorphophallus campanulatus / Elephant foot yam / O`l

Name of chemicals	Nature	Plant part	Properties
Salviasperanol	Di-terpene	Whole	Antibacterial, Antifungal & Cytotoxic.
Ambylone	Triterpene	Root & Tuber	Antibacterial, Antifungal & Cytotoxic.
3,5-diacetyltambulin	Flavone	Whole	Antibacterial, Antifungal & Cytotoxic
Polysaccharide	Sugar	Tuber	Splenocyte activation / Immune boosting.
Vitamin – E	Vitamin	Tuber	Antioxidant & Maintaining good health
1,3,5 – trihydroxy phenol	Phenolic	Tuber	Antispasmodic for any gastric pain or IBS.
Phyto-sterols	Sterol	Tuber	Anti-neoplastic, reduction of LDL &  Cholesterol.
Linoleic acid	UnsaturatedFatty acid	Tuber	Help maintain normal health producing PGs,  LTs And TBxs endogenously.
Oleic acid	Unsaturated Fatty acid	Tuber	Lowers LDL & increase HDL in plasma.
Myristic / Palmitic acid	Saturated Fatty acid	Tuber	Help synthesize Vitamin – A  But enhances LDL in plasma.

Pharmacological effects

Antibacterial and antifungal action – The extract of tuber, leaf and stem by alcohol, chloroform or aqueous medium shows strong antibacterial effect against Bacillus cereus, Bacillus subtilis, Staphylococcus aureus, Staphylococcus epidermidis, E coli, Proteus vulgaris, Pseudomonas aeruginosa and Klebsiella pneumonas etc. The antifungal effect is detected against Aspergillus flavus, Aspergillus Niger, candida albicans and Rhizopus oryzae. The identifiable compounds are Ambylone, Salviasperanol and 3, 5, -diacetyltambulin.

Antioxidant effect – Both alcoholic and aqueous extract of elephant foot yam display strong antioxidant effect which is seen to be more potent than any other solvent extracts. The presence of flavonoids, tannins and phenolics are considered to be the underlying cause because of their scavenging ability towards any generated free radicals like the superoxide anions or NO.

Anti-inflammatory and analgesic effect – The experiments on laboratory animals reveal that the methanolic extract of elephant foot yam can significantly exert analgesia dose-dependently (100 – 500 mg / Kg body wt) when administered peritoneally. The effect is very comparable to Diclofenac, commercially available non-steroidal anti-inflammatory drug. Similar way, anti-inflammatory effect is more pronounced for methanol rather than the CHCl₃ extract. It is also dose-dependent (200 – 400 mg / Kg).

Anti-nociceptive effect – In animal experiments using acetic acid induced pain model, the methanol extract shows significant pain inhibition (~ 46 %) at dose of 400 mg / Kg body weight.

Anthelmintic effect – The methanol extract of tuber shows higher activity in this regard compared to petroleum ether and CHCl₃ when studied against Pheretima posthuma (kind of earth worm) and Tubifex (sludge worm). The death and paralysis time are much comparable to drug, Albendazole. Seemingly, the effective component is tannin.

Hepato-protective effect – Extract by alcohol or water of tubers offers hepato-protection against Acetaminophen or CCl₄ induced liver injury in laboratory rats at 500 mg / Kg dose.

Chemoprevention against colon carcinogenesis – The dried methanolic extract of tuber shows good chemo-preventive effect against DMH induced neoplastic progress in rat colon. The effect has been identified due to the antioxidants like flavonoids and tannin plus several phyto-sterols present in the extract.

Miscellaneous effects –

1. Anti-hyperglycemic.
2. CNS depression activity.
3. Synergistic depression activity along with diazepam and phenobarbitone.

Sesbania sesban / জয়ন্তী।

General features: The botanical name of this plant is Sesbania sesban (SS) which is commonly known as Egyptian Sesban. In Bengali, it is called Jayanti (জয়ন্তী)।. It is a tropical plant that belongs to Fabaceae family of Sesban genus along with the five other members. The plant earns reputation for its medicinal significance. SS grows in many places of Africa, Australia and in India also several places of China. The origin of SS is much unknown. The plant is normally grown in agricultural areas for its unique ability to fix nitrogen in the soil. It is a perennial legume tree attaining to a height of ~ 30 ft and the diameter of stem is ~ 5 inches. The leaves are linear and oblong, 1.0 inch long and ~ 0.2 inch wide. The floral arrangement is inflorescenes which is 12 inches long and racemes holding approximately 2 to 20 yellow flowers striped with purple or brown streaks. The fruits are pods which are 5 – 8 inches long and slightly curved or occasionally linear holding 20 to 50 seeds. The young shoots are straight and green. The leaves, pods and flowers are used for edible purposes. The plant is included in the group of ‘fourteen vegetable greens’ (Choddo shak / চোদ্দোশাক।) which is normally consumed during Diwali festival in India. In that regard fresh new leaves and flowers are eaten after cooking along with the others mostly by frying chopped greens with spices. The young pods are cooked as vegetable curry. In many places of South East Asia, the matured and dried seeds are grinded and fermented to prepare a paste which is used as dips or dressings. But immatured seeds are not used due to toxicity. Even in case of use, they are kept soaking in salt water for at least three hours before the use. The dried stems and twigs are used for the firewood. The barks are employed for making fibers that provide good quality ropes. Due to its tropical or subtropical heritage, the plant cannot resist low temperature (~ 15C^◦) or heavy frost. In many regions, besides edible needs, various parts of the plant are emloyed to treat rheumatic swellings, high fever, boils and abcesses and anthelmintic needs.

Traditional medicinal uses: Most of the plant parts of SS find its appliactions to cure or prevent various diseases or disorders as indicated by Ayurveda. The seeds, bark and leaves are employed for menorrhagia, spleen enlragement, diarrhea and anthelmintic needs. The leaves have particularly antitumor, anthelminitic, antiinflammatory, antipyretic and contraceptive effects. Decoction prepared from leaf can treat sore throat, syphilis, gonorrhea and jaundice. The juice made of bark is able to treat dysuria. The oil from seeds have antibacterial, cardiac depressant and hypoglycemic property. Additionally, it has the spermicidal and hemolytic actions.

                                  Traditional medicinal uses of Sesbania sesban

Plant parts	Traditional uses
Seed	Astringent taste, Menorrhagia, Emanogogue, Spleen enlargement, Fertlity control,  and Diarrhea.
Seed oil	Cardiac depressant and Antibacterial.
Leaves & Stems	Antinflammatory, Dysuria and Sleeping aid, Antioxidant & Spermicidal.
Leaf juice	Anthelmintic, Antimicrobial, Antidiabetic.
Bark juice	For cutaneous eruptions.

Phytochemical property of chemicals present in Sesbania sesban: The seed of SS has several anti-nutritional factors eg, Tannins, Saponins and Trypsin inhibitors. These act as a problem for disallowing them to use as animal feed. Further, the seeds synthesize Olenolic acid, Stigmastane – 5.24(28)-diene-3β-O-β-D-galactopyranoside and Galactomannan. The extract has high level of Phenolics, Flavonoids, and Anthcyanins. The green pods and leaves have Campesterol, β – Sitosterol whereas the flowers contain Cyanidin and Delphinidin with glucoside linkage. Both pollen and pollen tubes have α – ketoglutaric acid, Oxaloacetic acid and Pyruvic acid. The extract from root shows Oleanolic acid – 3- β – glucuronide that has potent spermicidal activity. The glucuronide derivative of Saponin shows mollusccidal property. Further investigation shows that stem and root extract produces few alkaloids, phytosterols, flavonoids, oil and gums. The leaf extract has no fixed oil.

                                                            Major phytocomponents

Plant parts	Phytocomponents
Pods	Cholesterol, Campesterol, β – sitosterol, Kaempferol
Leaf	Crabohydrates, Glycosides, Proteins, Amino acids, Saponins, Tannins, Alkaloids, Phenolics, Flavonoids, Fibers, Oleanolic acid, Campesterol, Lupeol, Β – sitosterol, Cholesterol, Chikusetsu saponin, α – Amyrin, Lignoceric acid, Oleic acid, Stearic acid, Kaempferol.
Flowers	Cyanidin, Delphinidin glucosides.
Pollen	α – Ketoglutaric acid, Oxaloacetic acid and Pyruvic acid.
Seeds	Oleanolic acid, Stigmastane -5,24(28)-diene-3β-O-β-D- galactopyranoside and Galactomannan.
Root	Oleanolic acid 3 β – D- glucuronide.
Bark & Stem	Myo-inositol, Glucose, Fructose, Erythritol, Galactitol, Arabinitol.

The plant is a large reserve of triterpenes and practically all of them are identified as being beneficial for health. Those compounds provide numerous physiological benefits either to prevent or cure many illnesses. Additionally, the alkaloid Melatonin isolated in SS has proven its act as a sleeping aid. In a way, each individuals exhibit its pharmacological role. As for further example, Galactomannan is a dietary fiber that helps digestion. Stigmastane is an antiinflammatory steroid that acts by stabilizing the cell membrane.  Chikensetsusaponin offers cardio protection. Oleanolic acid and its derivative shows hepatoprotective and anti-tumor effects. Obviously, phytosterols are widely known for their beneficial role. Similar way, Flavonoids and anthocyanins in SS exert strong antioxidant and other useful effects that are immensely beneficial for cardivascular health.

Myo-inositol is often used for the reduction of diabetic nerve pain, insomnia, panic disorder, attention deficit hyperactivity disorder and promoting the hair growth. It also helps in the case of autism sufferers.

Cyanidin or Delphinidin is a potent chemopreventive agent naturally synthesized as plant pigment displaying natural colors. It belong to the category of anthocyanins. Anthocyanins are powerful antioxidants. They also inhibit UVB induced COX – 2 expression and PGE2 generation in skin cells thereby blocking the subsequent inflammatory responses. In addition, those compounds exhibit anti-neoplastic behavior. Essentially, they are beneficial for maintain the good health.

Pharamcological effects: The plant offers numerous pharmacological actions that are beneficial to health owing to its therapeutic uses for controling or preventing disorders and diseases.

Antiinflammatory action – The various extracts of SS leaves Show potent antiinflammatory actions when administered either topically and orally. The activity is quite comparable to non-steroidal antiinflammatory drug Diclofenac. The action could be mediated by the steroids, triterpenes and flavonoid components present in the leaf particularly, Stigmastane and Lupeol while blocking the COX – 2 enzyme and associated Arachidonic acid metabolic pathways.

Antidiabetic effect – The leaf extract indicates antidibatic potential when sunbjected to the experiments on normal and Streptozotocin induced diabetic animals. It lowers glycosylated hemoglobin but subsequently enhances serum HDL and Insulin with simultaneous lowering of blood glucose, LDL and Triglyceride. The effect is almost iedntical to the antidibatic drug Glibenclamide.

Antioxidant activity – The effect is seen dose-dependent when tested in vitro using alcoholic extract of leaves and flowers. The anti-oxidant action is evaluated following DPPH and NO scavanging action. At 100 µg / ml concentration the ability is ~ 77 %.

Antinociceptive effect – The aqueous and nonaqueous extract of wood stem or bark are subjected for evaluation following hot plate and acetic acid induced writhing test in mice. The effect is dose-dependent as well as very significant.

Antimicrobial effect – The extract of stem and leaves shows considerable antimicrobial effect against ten types of bacteria and five varieties of fungi species at a dose of ~ 500 µg / ml.

Fertility control and spermicidal action – The effect is noticed for seed extract or for its dried powder form after administering about 30 days using 250 – 400 mg / kg. Nearly, 100 % antifertility effect has been reached. For male animals genital organ is noticeably decreased. In case of females, shrinkage of uterus is noted. At higher dose of 400 mg / kg disruption occurs within ovary as well as in the endometrium. The identified component is Oleanolic acid 3-β-D-glucuronide which shows dose-dependent effect considering its spermicidal action. The effect is mediated while affecting the integrity of sperm membrane.

Anthelmintic effect – The aqueous or aqueous-alcoholic extract of leaves are potent against Moneiziaexpams (tape worm) and Paramphistomes (flat worms in cattle) at doses of 5 – 10 µg / ml to bring the complete paralysis.

Sleep aid – The leaves and stem extract acts as sleeping aid which is known for a long time. The recent study identifies the presence of Melatonin (~ 7.3 ± 2.8 ng / g) within the leaves and stems of SS. Melatonin isn a hormone produced normally within the Pineal gland that is widely known for its regulating effect on sleep-wake cycle. Logically, it could be the reason behind this effect of SS.

CNS stimulation effect – The extract of SS bark shows significant CNS stimulation when caffiene is used as being the control. No exact component has been identified yet.

 

Enhydra fluctuans / হিলমেচিকা / হিঞ্চে।

General features: It is an annual herbaceous edible tropical herb belonging to Asteraceae family, often used as vegetable green during cooking or salad, possessing slight bitter or no taste. The English or botanical name is Enhydra fluctuans (EF). It is a semiaquatic plant that normally grows in the aqueatic environment often mistakenly identified as Water cress / Helencha /হেলেঞ্চা, which belongs to Braceace family. In Bengali or Ayurveda, it is properly named as Hilmechika / হিলমেচিকা / হিঞ্চে।.  The plant, EF grows all over the South East Asian regions particularly in Malay, Sri Lanka and eastern part of India and Australia which is thought to be its native land. It is a prostrate and tends to spread on the surface whose stems are fairly fleshy and enlarges to about 1.0 ft in length. It is somewhat branched and rooting at the lower nodes also fairly hairy by the nature. The leaves are linear oblong about 1.5 – 2.0 inches in length, usually pointed at the tip and truncated at base also toothed at margins. The flowering heads have no stalks and stood at the angle between stem and the leaves. The flowers are white and greenish or greenish-white in appearance and the fruits are achenes enclosed by strong receptacles. In most cases, either the leaves or young plants are used for edible reasons. It is also one of the necessary items belonging to the members of celebrated ‘Fourteen vegetable greens’ (Chodddo Shak / চোদ্দো শাক), consumed during the Diwali festival (Lighting festival) in India.

Folk medicinal uses: As indicated by Ayurveda, EF has been used to treat liver disorders, skin and nerve disorders. In India, juice made from the fresh EF leaves are used as a tonic or else treatment for neuralgia and other nerve disorders or even as a laxative. In other South East Asian nations like in Malay, the young leaves are consumed mainly for the laxative reason. In Philippines pastes made from the fresh leaves are applied to the skin for any eruptions or infections. It is also frequently applied to the female breasts to control the inflammation. In many rural areas it is used to cure gonorrhea. The paste prepared from leaves is often applied to the forehead for the remedy of headache or cooling the body in summer or even during the high fever.

Important chemical constituents in EF:  Besides having the usual primary constituents like chlorophyll, starch, fibers and minerals, the plant is uniquely enriched with proteins and β – carotene. In addition, it possesses a large reserve of saponins and tannins. The other ingredients are Cholesterol, Myricyl alcohol, Sitosterol, Stigmasterol, glucosides, sesquiterpene lactones (Germacranolide, Enhydrin, and Fluctuanin) and few diterpenoid acids or their isovalerate or angelate derivatives. Other plant flavonoids like Gibberellins A9 and Gibberellins A13 are also isolated from the plant. Very minute level of alkaloids has been detected but none has been identified or characterized effectively.

The saponin found in EF has been analyzed to have the chemical structure shown below In general, saponins are known to have positive impact on health by lowering absorption of fats and lipids through the intestine subsequently reducing cholesterol and LDL level in circulation. Saponins also boost the immune system and helps maintain the normal body weight.

Myricyl alcohol or Tricontanol is along chain alcohol often synthesized within the plant. It acts as a growth stimulant to them.

β – Carotene is also an herbal product that helps produce vitamin – A by the enzyme cleavage. The enzymatic cleavage of one molecule of β – Carotene generates two molecules of Vitamin – A.

β – Sitosterol, the molecule is mainly synthesized within the plants. Although being phytosterol it acts a precursor to anabolic steroid Boldenone. β – Sitosterol has the property to reduce the level of circulating Cholesterol also enables to prevent or cure benign prostate hyperplasia (BPH).

Stigmasterol is unsaturated phytosterols which is metabolized to Progesterone, Estrogen and Corticoids. Those are important steroids needed for normal physiological functioning.

Gibberellins exist in different forms. They are plant growth hormones and diterpenoid acids by nature but not the flavonoids. Identification and characterization of bioactivity of Gibberellins brought the historic Green Revolution in the field of agriculture by boosting the food productions all over the world. It helps plant growth by breaking away the dormancy and enhancing the event of germination. It also catalyzes the breakdown of storage starch within seedlings at different stages producing glucose by inducing the enzyme α – Amylase which essentially causes rapid growth of the plant. Although few reports on animals indicate adverse health effects but nothing has been recorded about the human so far.

Germacrene lactones are widely known for their anti-mitotic and other biological actions acting against the tumor cells. The lactones have oxygen linking ring with carbonyl moiety at β position (O=C=CH₂) in the following figures. The unsaturated Carbonyl (= C=O) follow Michael type addition reaction with any nucleophiles within biological components like – SH or amino acid cysteine. The alkylation of thiol group affects number of biological function. Besides their oxygen rich assembly, it also helps plants survival from various predators and microbes. The beneficial actions on human health are anti-inflammatory, anti-tumor and antibacterial or anti-parasitic / antimicrobial effects. In many of the cases the action is somewhat specific. The structures shown below are Fluctuans – Enhydrin, Fluctuanin, Fluctuadin and two chlorine containing compounds, Melampolides.

Baicalein is a bioactive flavone having versatile physiologic role. It often has the glycoside linkages. It is a positive modulator of Benzodiazepine site or non-benzodiazepine site of GABA_A receptor inducing anxiolytic effect without causing sedation. It selectively works on the α₂ and α₃ subunit of GABA_A receptor. It is recorded that Baicalein can impose anti-depression effect. It also acts as an estrogen antagonist. Further it inhibits lipoxygenases therefore can act as an anti-inflammatory agent. In addition, it blocks the ET-1 induced proliferation of pulmonary arterial smooth muscle cells.

Mostly the hydrolysable tannins are noticed within EF which usually exert antioxidant effects as well as provides bitterness in taste without causing any significant de-proteinization within the physiologic system.

Pharmacological effects: The versatile uses of EF require to identify the mechanism behind its numerous pharmacological effects, which are seen to be beneficial for maintaining the normal health. Below is the list of few of them.

Anti-inflammatory effect – The experiments on laboratory animals following carrageenan induced paw edema or cotton pellet implanted granuloma indicated that extract of EF particularly the fraction enriched with flavonoids exhibits strong anti-inflammatory effect. The action is mediated via the inhibition of enzymes COX – 2 and 5 – LOX. The isolation of flavonoids eg, Baicalein is identified to block the metabolism of Arachidonic acid cascade subsequently exerting the anti-inflammatory role.

Antioxidant effect – The various extracts of EF show strong antioxidant actions when tested in different ways. The antioxidant property of EF is widely known. The extraction by ethyl alcohol shows the highest free radical scavenging ability that includes NO and super oxide and others. The presence of flavonoids and tannins could be liable behind this act.

Anthelmintic effect – The alcoholic extract of EF shows strong anthelmintic effect, which is vary comparable to the drug, Albendazole which works by binding to the colchicine interacting site of β – tubulin inhibiting the polymerization of microtubules but uniquely having more affinity toward β – tubulin of the parasites subsequently preventing the formation of spindle fiber essential during cell division.  But the exact mechanism in case of EF is not yet revealed. It is speculated that possibly by inhibiting spindle fiber formation inside the worm needed for the cell division it eventually causes dysfunction and death to the parasites.

Anti-clotting activity – It has been widely known that thrombolysis works by modulating the enzyme, plasminogen which works by dissolving the fibrin clot leading to solubilize and implicating its further proteolysis. But in that concern, the action of EF could be somewhat different. It is speculated that presence of numerous phytocomponents is in some way responsible for its thrombolytic behavior, but none are specifically identified neither the mode of action although the action is seen dose-dependent.

Antidiarrheal effect – Either the methanolic or aqueous extract can perform antidiarrheal activity on castor oil induced diarrhea. Further investigations indicate that aqueous extract inhibits / prevents the growth of S. aureus, S. dysenteriae and S. boydii whereas the methanolic extract partially inhibits S. flexneri, S. dysenteriae and S. boydii.

Hepatoprotective effect – The experiments on laboratory animal model using CCl₄ induced oxidative damage has shown that Ethyl acetate extract of EF, largely enriched with flavonoids offer significant hepatic protection by elevating the level of antioxidant enzymes with subsequent inhibition of lipid peroxidation.

Anticancer effect – The specific flavonoid fraction was tested for anticancer activity against Ehrlich’s ascites carcinoma in Swiss albino mice. The flavonoid glycosides of Baicalein (Baicalein – 7 – O-glucoside and Baicalein – 7 – O – di-glucoside) are identified to provide durable anticancer / antitumor actions reducing significantly tumor volume as well as enhancing the life span of experimental animals.

Miscellaneous actions – A) Phagocytic and cytotoxic activity, B) Neuroprotective potential, C) CNS depression action, D) Analgesic activity, E) Antidiabetic activity.

 

Alternanthera sessilis / Sessile joywood /শালিঞ্চে / শাঞ্চে।

General features: The plant is named as Alternanthera sessilis (A sessilis) or Sessile Joywood. In Bengali, it is called Shalinche / Sanche (শালিঞ্চে / শাঞ্চে).  So far, it only exists in two varieties, green and red. The red coloration arises due to the production of few anthocyanidine derivatives that are essentially the metabolites of chlorophyll. Regarding other ingredients, they are about the same by nature. The herb tends to grow all around the tropical and subtropical regions of the world. It belongs to Amaranthaceae family. It is a perennial creeping plant that sprouts in high humid or aquatic places like swamps, ditches or inside the shallow rice fields. It grows to about 3.5 ft tall. The origin of A sessilis is somewhat unknown although often claimed to be the native of Brazil. It is also considered to be an aquatic plant. Hence it is often noticed to be kept inside the aquarium for home decorations. But interestingly it would not grow any bigger under the submerged condition. It has been cultivated in the southern territory of United States and South American nations. The plant is also spotted in India, Sri Lanka and other South East Asian territories. In many rural areas, it is used in a significant extent. It has prostrate stems hardly ascending but frequently rooting at the nodes. The leaves are obovate or occasionally linear-lanceolate which is 4 – 6 inches long 1- 1.5 inch wide. The petioles are 0.05 – 0.2 inch long. The flowers are white and shiny. They are spiky bract which are about 0.03 – 0.06 inches long and glabrous. Generally, the plant flowers from December until the end of March. Often, it is used for food particularly in the South East Asian countries either as an ingredient of salad or as cooked vegetable. The taste is very identical to spinach. Uniquely, the herb has large content of potassium and calcium. Fresh green leaves have ~ 1000 mg / 100 g of potassium and ~ 500 mg / 100 g of calcium. As per the Hindu rituals, following the traditional customary, it is consumed as vegetable green particularly a day before the Diwali festival in India. It is one of the members of traditional ‘fourteen vegetable greens’ (Choddo shak / চোদ্দো শাক).  The tradition still persists in the Northern and Eastern part of India. The wild herb, besides having food and medicinal uses is further utilized as poultry feed, ornamental plant (especially the red colored variety) for hedging. The extract of stems and leaves are conventionally used for treating the eye trouble in the villages. It is also frequently administered preventing the vomiting of blood. The herb has special ability to restore sexual virility. The poultice made out of fresh leaves are used to control or cure the boils or infections on skin. It exhibits potent diuretic action along with tonic and laxative effects. It is used for treating dysuria and hemorrhoid. It is employed further in cosmetics for preparing medicinal hair oil and natural mascara, named Kajal (কাজল) for the beautification purposes of women.

Folk medicinal use: According to Ayurveda, the plant shows anti-pyretic, lactogenic, wound healing, anti-diabetic and blood purifying role. In many regions of India it has been used as eye tonic. A sessilis also has the strong antioxidant, anti-microbial, anti-bacterial, hepato-protective, anti-inflammatory and hematinic actions. Owing to its antibacterial property, the plant is effective against gonorrhea. In frequent occasions it is also employed for remedying headache, dysentery and diarrhea. These acts presumably rely on the presence of flavonoids, triterpenes, tannins, phenolics, saponins and other aromatics synthesized within the plant.

Traditional / Folk uses

Parts	Uses	Way of application
Stems & leaves	Gastric and stomach problems, anti-ulcer effects	Leaves and stems are roasted and Orally taken.
Leaves and shoots	Galactogue, fodder and night blindness.	Orally taken similar way.
Shoots	Vegetable	Cooked
Whole plant	Prevent dementia, enhancing virility and immunity.	Cooked
Whole plant	Cures diarrhea, leprosy, skin diseases, fever and stomachache.	Extract and poultice
Leaves	Stomachache	Fried in butter / ghee with black Pepper and salt for 2 -3 days.
Root, stem & leaf	Blood dysentery	Decoction twice a day.
Whole plant	Blood & skin diseases,  hair growth also inducing  lactation	Juice.
Leaves	Eye disease	Consumption periodically.

Chemical constituents: Uniquely, the herb shows large reserve of Potassium and Calcium compared to the other minerals. The analysis reveals its mineral content per 100 gm of dry material as: Na – 286 mg, K – 4500 mg, Ca – 520 mg, P 50 mg, Mg – 80 mg, Zn – 10 mg, Fe – 10 mg, Cu – 1.6 mg, Mn – 7 mg, Cr – 7 mg.

 The major phyto-chemical constituents in A sessilis are flavonoids, triterpenes, carotenoids, saponins and steroids / sterols. A few of them serve as a part of the defense mechanism acting against predators like insects, microbe and herbivores. The ethanolic or aqueous extracts of aerial parts shows nootropic effect helping enhance the cognitive functions. The fledgling sprouts contain various triterpenes, carotenoids, steroids, flavonoids, saponins and several sterols. Among the flavonoids the noticeable ones are Vitexin, Quercitin, Rutin, Catechol, gallic acid and ellagic acid. In addition to other components, the root contains significant level of Lupeol, widely known triterpenoid. Besides having the individual role, these compounds in concerted way exhibit anti-inflammatory, antimicrobial, anti-protozoal and anti-tumor properties. They also act as powerful antioxidants thus help scavenging the ROS, or any free radicals generated indigenously which might be the basis of preventing or curing numerous diseases.

Flavonoids and Phenolics in A Sessilis

The phyto-sterols are widely known for their beneficial effects on health. Most of them normally affect the cholesterol absorption within body perhaps via the intestine subsequently lowering the risks of cardiovascular diseases. Among the cholesterol lowering behavior Campesterol and α – Spinasterol are noticed to be the more potent. Besides the general behavior, most of the individuals have other specialties. For example, β – sitosterol prevents benign prostate hyperplasia (BPH). Whereas, stigmasterol acts as a precursor to synthesize Boldenone, an anabolic steroid acting for the enhancement of human and cattle growth.

The other phytocomponents are Pheophytin A & A`, Oleanolic acid, Cycloeucalenol, Phytol, and 24-methylene cycloartenol. The Pheophytin derivatives apparently look like Chlorophyll lacking Mg⁺² at the core. They usually are intermediate components in the electron transfer pathway during photosynthesis. Cycloeucalenol molecule takes part in the biosynthesis of phyto-sterol which also has the role in the reduction of cholesterol in circulation. Oleanolic acid, a triterpenoid shows potent anti-tumor, anti-viral, anti-inflammatory and hepatoprotective affect. Regarding Phytol, it has anti-nociceptive and anti-convulsing effect.

Pharmacological actions of A sessilis: The extracts of A sessilis display numerous pharmacological properties. Some of them are described below.

Anti-microbial, anti-fungal and Antioxidant effect – The extract inhibits several bacterial and fungal strains. The antifungal action is caused due to its interactions with three target proteins, 14 – α – sterol demethylase, Mevalonate 5 – diphosphate decarboxylase and N- myristoyl transferase. Among them the highest affinity is noticed toward the first one. The identifiable compound for antifungal action mainly relies on 3,3` – (propane – 2,2` – dyl) bis (3,4,5,6,7,8 – hexahydro – 1H-isochromene) found in the ethanolic extract of leaves, shown below. The plant also shows strong antioxidant potential due to its large reserve of flavonoids.

Anti-inflammatory effect – The fresh leaf extracts by CHCl₃ or petroleum ether shows potent anti-inflammatory properties as evidenced by the animal experiments. The potency can be comparable to Diclofenac, a commercial known over the counter non-steroidal anti-inflammatory drug (NSAID) that acts by blocking the COX – 1 & 2 preventing the Prostaglandin synthesis from Arachidonic acid. The extract follows the identical course while blocking the same enzymatic interactions. Further investigation reveals the identifiable components are mostly the sterols present in leaf extract.

Anti-cancer effect – Studies on various cancer cell lines using particularly colorectal (HT-29) and breast cancer (MCF-7) cell lines and others show that ethanolic extract of leaves have strong cytotoxic effect by inducing anti-proliferative as well as apoptosis in dose-dependent manner. Among the extracts from other parts, the leaf extract displays the most potency. Further investigation identifies the several triterpenoids and possibly the sterols could be liable for this act.

Anti-diabetic and anti-hyperlipidemic effect – The in vivo experiments using Streptozotocin induced diabetic rats showed potent reduction of blood glucose with subsequent lowering of cholesterol, LDL and Triglycerides. The leaf extract is seen to be more potent in that context. Further experimentations reveal that stimulated Insulin release from the pancreatic β – cells are the primary factor behind this effect.

Antioxidant effect – Both ethanolic and aqueous extracts show strong antioxidant activity along with the free radical scavenging actions. The large reserve of flavonoids and phenolic components like Ferulic, Vanillic acid, catechin and epigallocatechin are identified to be major factors.

Analgesic effect – The experiments on laboratory animals using ethanolic extract of fresh leaves shows analgesic effect. The effect is seen to occur both centrally and peripherally. The identifiable compound is Lupeol. Lupeol is known to exert analgesia under inflammatory condition by inhibiting IL-4, IL-5 and IL-13. The possible effect of other sterols could be responsible also in the analgesic action.

Hematinic effect – The extract of leaf or whole plant can exert significant hematinic effect which has been verified in the laboratory experiments by using the animal models. The level of Ferritin has been increased in all types of experimental animals whether mice or rats, when anemia is induced artificially by bleeding.

Cassia sophera / Sena sophera / কলকাসুন্দি

General features: The shrub is commonly known by the name Sena sophera. Its English name is Cassia sophera (C sophera). In India, it is called Kasundi in Hindi whereas in Bengali, its name is given Kolkasundi (কলকাসুন্দি). It is a tropical plant that normally grows in the wastelands or forests. It is a genus of Cassia Linn and belonging to Fabaceae family (Caesalpiniaceae subfamily). There are about 600 species widely distributed all over India and other tropical regions of the world. It is presumably originated from India / Bangladesh or other South East Asian countries and in some places of Southern China. Besides the Asian nations, it is also found in several South American and African countries. The shrub is used as a folk medicine in rural areas mostly for treating respiratory ailments. It is a good source of mucilage, flavonoids, polysaccharides and Anthraquinones. Phytochemical identification indicates that it provides high level of antioxidants. Although considered being a medicinal plant but frequently used for edible purposes as a vegetable green particularly the leaves or green pods cooked with spices. Normally, the fresh pods are used to make curry. Whereas the dried seeds and leaves are occasionally used as substitute for coffee. The plant reaches to a height of ~ 10 ft. The leaves show insect repellant property. It is often allowed grow along with the other crops. This practice prevents damages from the land snails. Due to insecticidal action, dried leaves are stored with stockpiles of grains. The plant has ability of fixing nitrogen in the soil. It is also used for the ornamental purposes for bright yellow flowers which are racemes by nature. The leaves or leaflets have tapering at the end with single gland at the base. In recent days, the use of various members of Cassia are rising. C sophera is particularly one of them. The plant possesses enormous medicinal potential while acting as anti-oxidant, anti-microbial, anti-parasite, anti-inflammatory, and anti-diabetic and other beneficial role. Due to its large reserve of anthraqunone derivatives it also acts as good laxative.

Folk / traditional medicinal uses: The leaves are mostly utilized for traditional folk medicine that contains high level of Kaempferol and Anthraquinone derivatives (Chrysophanol, Physcion, Rhein, Emodin and others). Those components are known to have anthelmintic, expectorant and febrifuge effects. The infusion prepared from leaves can control or cure rheumatism, fever, inflammation and malaria. The leaf extract is able to cure conjunctivitis also helps healing wounds and cure ringworm infection. The extract also shows anthelmintic property. The decoction made of roots or barks helps relieving painful menstruation also, if given to children can stimulate the nervous system. The bark extract can efficiently control diabetes. The extract of entire plant can restrain epilepsy. The seeds reduce fevers also treat nephritis or Bright’s disease. According to the Unani medicine, also mentioned in ethno-pharmacological literature, the herb is highly effective in treating Pityriasis, Psoriasis, Asthma, acute Bronchitis, Cough, Diabetes and convulsions among the children. It is also effective in controlling osteoarthritis.

Chemical components: The major phyto-chemicals in C sophera are alkaloids belonging to Piperidine family, flavonoids (rutin, rhamnetin, kaempferol and quercetin), Anthraquinones and essential oils which have numerous terpenes and long chain fatty acids. Advantageously, the essential oil extract from C sophera is used for preserving food and beverages because of the antimicrobial constituents. Usually, essential oils are counted to be non-toxic but active against numerous micro-organisms although the limit to be added should be judiciously considered since it may create adverse reactions like nausea, vomiting or irritability on skin. But majority of Cassia species have noticeably large content of Anthraquinone derivatives either in free or with glycosidic linkage.

Naturally occurring Anthraquinone derivatives in Cassia sophera

Anthraquinones are the organic molecules having 9, 10 di-oxo-anthracene moiety. Until now, about 79 naturally synthesized anthraquinone derivatives are identified. Among them the notable ones are Emodin, Physcion, Rhein, Chrysophanol and Sopheranin and few others. They have been known widely for bioactivities while working as anticancer, anti-inflammatory, diuretic, anti-diabetic, vaso-relaxing and exhibiting phyto-estrogen actions. They are seen particularly effective against tumor proliferation and auto-immune disorders. In that way, many of the anthraquinone derivatives help prevent from life threatening metabolic problems.

Interestingly, replacing any of the side groups by – OH, the molecule(s) is often referred as hydroxy anthraquinone(s) which displays the bright color by absorbing light at the visible range of wave length. Usually, anthraquinone derivatives have their characteristic absorption spectra. The existence of typical chromophore like conjugated double bonds produces strong absorption at the UV region. The UV absorption majorly occurs due to benzenoid transitions in addition to the absorption by the quinonoid groups displaying peaks around 240 – 260 nm having the high intensity at 250 nm also around 320 – 330 nm with medium sized peak, further especially at 322 nm. The quinonoid band appears at 260 – 290 nm. Those characteristic band patterns are not tremendously affected by the substitution on phenol rings. The unsubstituted anthraquinone has small peak at 405 nm thereby displaying light yellow color. The substitution at 1 and 4 positions causes strong bathochromic shift intensifying colors more than any other substitution. Usually, the colors of naturally occurring anthraquinone derivatives vary from light yellow to dark red, brown and pink or violet. Owing to its quinonoid moiety, anthraquinones can efficiently take part in the redox reactions exerting both anti-oxidant and pro-oxidant reactions. Emodin and Physcion acts as anti-oxidant causing anti-microbial effect. As per the exception, only a few expresses pro-oxidant behavior. For example, Chrysophanol accelerates peroxidation of Linoleic acid. Chemically, anthrone, anthraquinones and substituted anthraquinones particularly with phenolic –OH at C1, C6 and C8 and even with methylated (-CH₃) group at the C3 position act as anti-oxidant displaying significant scavenging of generated free radicals. The order of anti-oxidant activity is, Anthrone (95 %) > Alizarin (93 %) > Aloe-emodin (78 %) > Rhein (71 %) > Emodin (36 %) > Anthraquinone (8%). Experiments convinced that the anti-oxidant behavior of these derivatives are mostly due to the scavenging effect of free radicals also including the innate reducing ability. On the contrary, the pro-oxidant effect of Chrysophanol is exerted by enhancing the free radical production. Further it has been also established that these derivatives act as good metal chelating agents. They can efficiently chelate the toxic metal ions like, Cu⁺², Al⁺³, Hg⁺² and Cd⁺² or others of similar category. The chelation of mercury by natural anthraquinones produce non-toxic complex thereby relieving the intracellular – SH group(s) free to work accordingly. Most of the anthraquinone derivatives show anti-tumor activity due to the cytotoxic effect on those cells. In frequent occasions, they are able to control multi-drug resistance cancer cells by inducing apoptosis following different intracellular pathways as seen in case if breast adenocarcinoma, MCF-7 while arresting the cell cycle at G1 phase. Experiments show that numerous cancer / tumor cells stop proliferation when exposed to different naturally occurring anthraquinone derivatives. Emodin can suppress cervical cancer by blocking neo-vascularization and promoting the apoptosis. Emodin also inhibits the growth of pancreatic cancer cell line, PANC-1 by demethylating the tumor suppressor gene. Although Emodin shows many of its anti-cancer properties but FDA has not approved it for treatment since it is also a potential carcinogenetic substance. Further it causes diarrhea, nausea and renal failure. It has been noticed that even majority anthraquinones have great potential as anti-cancer drugs controlling versatile categories of cancers but its application is also a major concern so it should be administered very judiciously.

Major anthraquinone products in C sophera

Regarding anthraqunone content, the derivatives are synthesized slight differently in parts of the plant. Leaves and flowers have most of the Sennoside isomers and Chrysophanol whereas the roots and barks have 1,8-dihydroxy-2-methyl-anthraquinone, Chrysophanol, Physcion,1,8-dihdroxy-3,6-3,6-dimethoxy-2-methyl-7-vinyl-anthraquinone, 1,3-dihydroxy-5,7,8-trimethoxy-2 methyl-anthraqunone and heartwood has 1,2,7-trihydoxy-6,8-dimethoxy-3-methyl anthraqunone, 1,2,6-trihydroxy-7,8-dimethoxy-3-methyl Anthraquinone, Chrysophanol, Physcion, Emodin and Sopheranin.

Flavonoids in C sophera

The plant has appreciable amount of flavonoids. Among them, the majorly found ones are, Quercitin, Rhamnetin, Kaempferol and Rutin. The beneficial effect of them are widely known. The flavonoids are poorly absorbed in the human body (~ 5 %). It is also quickly metabolized and excreted. So it has been presumed that the anti-oxidant effect in blood is mostly due to the production of Uric acid but less from the absorbed intact flavonoids. The further physiologic effect is provided by its scavenging action on generated free radicals. Adding those together, it is quite evident that flavonoids are overall beneficial to health while acting as anti-inflammatory, anti-cancer, anti-bacterial as well lowering the risks from cardio-vascular diseases. Besides the flavonoids, there are also appreciable amount of tannins present in the plant. Flavonoids are widely for its beneficial role in health especially acting as good anti-oxidant. In general, they act as anti-inflammatory, anti-cancer, anti-diabetic and simultaneously lower the cardio-vascular risks by lowering the cholesterol and lipids in circulating plasma.

Major flavonoids in C sophera

Piperidine alkaloids

Most of the Cassia species synthesize several Piperidine alkaloids which is noticed also in C sophera also. Piperidine moiety is the characteristic of this alkaloid. About 700 of them are identified in both plant and animal kingdoms. Some of them possess high level of toxicity. They are widely known for anti-cancer, anti-bacterial, anti-histaminic, herbicidal, fungicidal and insecticidal properties. In addition they have potent actions on central nervous system while acting as stimulant as well as depressant also impose actions by interacting with the nicotinic receptors within neuromuscular joints.

Essential oil

The leaves of C sophera is the major source of essential oil (~ 0.8 % w / w). Approximately 29 components have been identified having 94.1 % oil composition. The major ones are Benzyl alcohol (9.1 %), Iso-eugenol (5 %), Germacrene D (4.8 %), Iso-creosol (5.7 %), Phenyl ethyl alcohol (5.1 %), Azulene (4.7 %) and Linolenic acid (1.6 %). Benzyl alcohol acts bacteriostatic, preservative and used against removing head lice. Iso-eugenol exists in cis – and trans – isomers. Both of them find uses in cosmetics. Germacrene D is a sesquiterpene which shows antimicrobial and insecticidal properties. It plays the role of insect pheromone. Iso-cresol has strong antimicrobial effect. Phenyl ethyl alcohol has the pleasant odor which is produced by the fungus named Candida albicans exerting anti-microbial and preservative effects. Azulene is a pigment displaying the blue color and often used in the cosmetics. Linolenic acid is a ploy-unsaturated fatty acid exists in ci s– and trans – forms having several isomers showing olefinic bonds at different positions creating α – (ω -3 or n – 3 fatty acid) and γ – (ω – 6 or n – 6 fatty acid) isomers. They are actually dietary components having distinctive beneficial role on health. The large variety of individuals show anti-bacterial and anti-microbial effect. In that context, the use of essential oil as a whole is noticed to have the potent anti-bacterial effect also for human pathogenic and bacteria from the soil. The extracts by any solvent either hexane, ethyl acetate or alcohol show almost the similar anti-bacterial behavior with slight variations.

Pharmacological actions of C sophera: The plant has large potential for medicinal actions. In that regard its pharmacological effects needs to be highlighted since several activities may not be beneficial for health. Following is the discussion about some of the important pharmacological effects.

Analgesic effect – The seed extract of C sophera induces analgesia centrally as indicated by the laboratory experiments using external thermal nociceptive stimuli confirming the opioid type analgesic effect. The inhibitory effect of flavonoids on pain perception has been well documented which occurs due to the prevention of generation of inflammatory mediators. It has been further recorded that flavonoids can enhance the serotonin level which in turn interacts with the receptors 5-HT2A and 5-HT3 producing analgesic action centrally. In a way, both anti-inflammatory and analgesic actions are credited for those flavonoids present in seed.

Anti-oxidant effect – In vitro experiments indicate that the constituents present in the extract of C sophera have strong free radical scavenging ability. The identifiable components are mostly flavonoids or glycosides.

Hepato-protective effect – Applying experimental animal model while inducing hepatic damage using CCl₄, it has been reported that ethanolic extract of C sophera leaves can efficiently prevent the injury. The fact has been verified biochemically and histo-pathologically. The leaf extract can bring back the level of AST, ALT and ALP and total bilirubin content to normal. The identifiable constituents are flavonoids.

Hypoglycemic and Hypolipidemic effect – The aqueous extract of C sophera leaves exhibits potent hypoglycemic effect by enhancing the peripheral glucose level within Streptozotocin induced diabetic laboratory animals. It also significantly lowers the elevated level of Glycosylated hemoglobin (HbA1C) ~ 50 % with simultaneous increase of insulin level (~ 41 %). The level of total cholesterol (~20 %), LDL (~ 22 %) and triglycerides (~ 58 %) in circulating also decline considerably. The further investigation indicates that the leaf extract has strong stimulating influence on pancreatic β – cells to release insulin and the effect is not mediated by the K-ATP channel. Although no definite compounds are identified but the suspected agents might be the combination of alkaloids and flavonoids.

Anti-inflammatory effect – The ethanolic extract of leaf shows significant anti-inflammatory action when tested on the laboratory animals. The level of PGE₂, PGF₂ Serotonin and histamine are seen to be alleviated including the peptide Substance P. The identifiable components are flavonoids and saponins. Among them Rhamnetin is noticed to be the predominant factor.

Anti-asthmatic effect – The extract of C sophera shows potent anti-asthmatic behavior due to its anti-allergic, anti-histaminic and anti-inflammatory as well as adaptogenic properties. It also works as an effective bronchodilator while preventing or controlling the asthma attack.

Anti-bacterial effect – The ethanolic extract of C sophera leaves can efficiently control the growth of numerous pathogenic bacteria from the soil. The identifiable components are within the mixture of essential oils which contains ~ 29 components.

Laxative effect – The strong laxative effect of C sophera has been noted for a long time. The identified compounds are anthraquinone alkaloids along the mucilages built in the plant.

 

 

Tinospora cordifolia / Guduchi / Amrita / গুলঞ্চ

General features: This perennial plant is commonly called Heart-leaved moonseed or Guduchi / Giloy. The botanical name is Tinospora cordifolia (T cordifolia). In Bengali, it is named as Guloncho / গুলঞ্চ.  It also bears the name Amrita in Hindi and several other languages, including Sanskrit (Ancient Indian language) meaning ‘immortality’. The shrub has been extensively studied for its large phytochemicals reserve which are versatile by the nature and immensely beneficial for human health. In addition, the herb shows unique mineral content eg, Potassium (~ 46 mg / g), Calcium (5.5 mg / g), Iron (0.4 mg /g), Copper (0.16 mg /g) and Zinc (0.1 mg / g). It is an herbaceous vine belonging to Menispermaceae family, a native of tropics like, India, Sri Lanka and Myanmar. The deciduous shrub spreads considerably by climbing with twining branches. The leaves are simple, alternate with long petioles about 6 inches long, round or pulvinate at the base and apex. The basal one is longer and partially twisted and half way around. The lamina is broad and ovate or ovate-cordate 4 – 8 inches long and 3 – 7 inches broad and deeply cordate at the base and prominent reticulum beneath. The flowers are greenish yellow in color and unisexual by nature. The flowers appear when there have less leaves. Male flowers are clustered whereas female ones are solitary inflorescence. Flowering occurs between the months of March and June. Fruits are aggregate of 1- 3, ovoid smooth drupelets on thick stalk bearing scarlet orange colors. In many areas the shrub has been cooked and consumed as vegetable green especially during the autumnal season being a part of Hindu ritual during Diwali Festival that dictates to use fourteen vegetable greens (চোদ্দ শাক). T cordifolia is one of them. Essentially, it is a medicinal plant often used in numerous Ayurvedic medications to treat or cure various ailments practiced for centuries in India and other South East Asian nations. In ancient times, in Indian subcontinent, it is also used for treating bacterial infections / sexually transmitted diseases like Gonorrhea and Syphilis. As per additional measure, the plant shows strong diuretic and tonic property. Currently, it is seen to have controlling effects on HIV infections. The tincture prepared from T cordifolia finds official recognition in Indian Pharmacopoeia. As a folk medicine, it is still used to cure general weaknesses, fever, dyspepsia, dysentry, syphilis, impotency, gout, viral hepatitis, skin diseases and anemia. It enables to cure or prevent arthritis, diabetes, hepatitis and jaundice. The shrub also exerts emetic effect. In recent days, the plant draws large attention for its extraordinary medicinal role on health including anti-malarial, anti-neoplastic, anti-inflammatory and immune-modulatory effects. The major chemical components have been identified and well-characterized by the numerous pharmacological studies acknowledging distinctly their biological role on health.

Ethnomedicinal / folk uses: Various parts of the plant are used as folk medicine eg;

Leaves – Used for treating gout and ulcers.

Fruits – The dried fruits mashed with honey and ghee is used as tonic or treating for jaundice and rheumatism.

Root – The aqueous extract is used to treat leprosy (Mycobacterium lepromatosis), gut obstruction and acting as emetic agent.

Stems – It is used to treat numerous diseases eg, diabetes, arthritis, inflammation, liver problems, blood problems, cardiac problems, skin diseases and many others.

Natural components: A very large variety of phytochemicals have been identified from different parts of the plant. Those are categorized as alkaloids, diterpenoid lactones, steroids, glycosides, aliphatics and polysaccharides. The table summarizes several of the biological effects relating chemical contents and its actions.

Major categories of phyto-chemicals in T cordifolia

Medicinal uses: According to ancient Ayurveda, T cordifolia was used to enhance the vitality. The recent scientific research confirms its many beneficial effects on health that includes diabetes, inflammation, glucose metabolism, neurology and immune system. The use of T cordifolia acts as immune stimulatory. It is seen potent to be an anti-allergic supplement. As per further addition, its consumption benefits patients suffering from the diabetes. It helps lower the absorption of sugar produced from the metabolism of carbohydrate. It enables to reduce diabetes related pathologies like retinopathy, neuropathy or nephropathy. It is a Mono amine oxidase inhibitor (MAO) aiding to enhance the level of Catechol amine / Dopamine in brain. The plant synthesizes few phyto-androgens thereby helping protect from the damage of DNA induced by the radiation or any environmental toxicity. The plant also behaves like an adaptogen thereby improving the resistivity against any stress.

Identified chemical components and its physiologic effect: The major phyto-chemicals isolated from various parts of the plant body, root, stem, leaves and others fall into the categories like, alkaloids, diterpenoid lactones, aliphatics and glycosides. T cordifolia also synthesizes various steroids like Tinosporine, Tinosporides, Tinosporoside, Cordiofolids, Cordiofol, Hepatocosanol, Clerodone, Furano diterpene, Diterpenoid furano lactone tinosporidine, Columbin and β – sitosterol. Additionally, the plant is also enriched with protein (11.2 %) and loaded with Calcium and phosphorous. All those individually or concertedly exert beneficial effects by acting as anti-oxidant, hepato-protective, anti-inflammatory, anti-spasmodic, anti-osteoporotic, anti-diabetic, anti-allergic, anti-microbial, anti-neoplastic, and anti-stress and various others. Below is the list of several compounds found in different parts of the plant.

Bio-active phytochemicals in T cordifolia and its respective physiologic role

Category	Compounds	Plant  sources	Biological effect
Alkaloids	Beberine, Choline, Palmatine, Tembeterine, Magnoflorine, Tetrahydropalmatine, Tetra hydro Jatrorrhzine, Aporphine Alkaloids, Tinoscorside A, Tinoscroside B.	Stem & Root	Anticancer, Anti-inflammatory, Immuno-modulatory, Antiviral Infection, Anti-diabetic also for Treating Neurological and Psychiatric Conditions.
Glycosides	18 – norclerodane glucoside, Furanoid diterpene glucoside Tinocordiside, Tinocordiofolioside, Cordioside, Palmatosides.	Stem	Treating neurological problems, Eg, Parkinson, ALS, dementia, Cognitive deficiencies, loss of Neurons within spine and Hypothalamus, Immunomodulation : Increase of IgG and macrophage activation, Inhibition of NF – κβ, scavenging NO and exerting anticancer effects.
Diterpenoid lactones	Furanolactone, Clerodane Derivatives, Tinosporides, Tinosporine, Isocolumbin, Columbin.	Entire plant	Vasorelxant: relaxing norepinephrine induced contractions, Inhibits Ca+2 influx, Anti-inflammatory, anti-microbial, Anti-hypertensive, Anti-viral. Inducing apoptosis in Leukemic, cells by activating Caspase – 3 and Bax & inhibiting Bcl-2.
Steroids	β – sitosterol, Ecdysone, Hydroxy-ecdysone, Giloinsterol.	Aerial stem	Induces cell cycle arrest at G2/M Phase and apoptosis suppressing c-Myc, inhibits TNF – α & COX-2.
Aliphatics	Octacosanol, Heptacosanol, Nonacosan.	Entire Plant.	Anti-nociceptive, anti-inflammatory, Protection against 6 – hydroxy dopamine Induced Parkinsonism. Down regulates VEGF, inhibits TNF-α, From binding to DNA.
Miscellaneous	Jatrorrhzine, N-tans- feruloyl Tyramine, Giloin, Tinosporic Acid, derivatives of Tetrahydrofuran.	Whole Root.	Protease inhibitors for both Non-resistant and drug resistant HIV. Tyramine is Neuromodulator used in treating Depression.

Alkaloids: Among the constituents in T cordifolia, alkaloids of iso-quinoline moiety are the distinguishing components because of the prominent and closely related physiologic actions. A few of them are discussed below.

Berberine – It is an important plant alkaloid, heavily used in Chinese folk medicine. At present, modern medicine confirms many of the impressive uses. Berberine works by activating AMP-activated protein kinase (AMPK) which intensely regulates metabolism of the organs. It has potent anti-diabetic property helping type – 2 diabetic patients by, A) decreasing insulin resistance making Insulin more effective; B) Increasing glycolysis helping breaking down sugars inside the cells; C) Reducing sugar synthesis in liver; D) lowering the breaking down of carbohydrates; E) enhancing the production of beneficial gut bacteria. Alongside it lowers the level of Hemoglobin A1c quite significantly. Further, it helps the lowering of cholesterol in circulation thus reduces the chances of heart attack. Berberine is also a powerful anti-oxidant. It has more health benefits while acting as anti-depressant, anti-neoplastic, preventing fatty liver formation and also as powerful anti-microbial agent.

Palmatine – The compound Palmatine and Berberine and several of the isoquinoline category of alkaloids finds potential medicinal uses in treating diseases like Jaundice, Dysentry, Hypertension, Arrhythmia and Inflammation also in preventing / curing several of the liver diseases. Additionally, it has potent anti-microbial effects in controlling deadly viruses including Flavivirus (causing Encephalitis) and West Nile Virus, NS2B-NS23. It also shows anti-malarial property. Palmatine blocks delayed rectifier K⁺ – ATP and stimulation of Na⁺ – Ca⁺² exchanger and inhibits the L- type Ca⁺² current. It prolongs ventricular action potential in the heart, suggesting its possible use in treating arrhythmia and heart failure. Further it attenuates Ca⁺² activated Cl^– secretion via the inhibition of basolateral Charybdotoxin (scorpion venom – 37 AA peptide neurotoxin, blocks Ca⁺² activated K⁺ channels inducing paralyzing effect on muscles) sensitive (SK4) K⁺ channels also inhibiting cAMP activated Cl^– secretion by blocking the CFTR Cl^– channels. In this way, it exerts strong anti-diarrheal effect. Additionally, it reduces Osteoclast differentiation by inhibiting RANKL (a membrane protein, member of the TNF superfamily affecting bone generation) and OPG (Osteoprotegerin, bone generation factor) expression by the osteoblasts. In a way, it acts as an anti-resorptive agent for the Osteoporosis therapy. The compound and extract of T cordifolia show significant anti-leukemic role as studied in vitro using the HL – 60 cells. The anti-cancer action could be due to the inhibition of Reverse transcriptase and Topoisomerase I and II. Both Berberine and Palmatine can bind to DNA and induce Guanine specific DNA photo-oxidation via singlet oxygen (¹O₂) formation. In that way they are used for the photo-dynamic therapy.

Tetra-hydro-Palmatine – The levo enantiomer of Tetrahydro-palmatine is an extremely active agent thus being used for clinical purposes naming “Rotundine”. It is an active antagonist toward the Dopamine D₁ and D₂ receptors but also interacts with the D₃, α – adrenergic and several of the Serotonin (5 – HT) receptors too. It also acts as a partial agonist to D₁. The very high affinity toward D₁ and D₂ distinguishes it from the available Dopamine antagonist drug Haloperidol. The levo enantiomer also interacts with the D₃ receptor which is the interest for the anti-addiction effect. D₃ is liable for the addiction behavior therefore blocking D₃ may prevent the relapse effect.

Choline – It is found both in plant and animal kingdoms. The compound is a precursor of important neurotransmitter Acetyl choline. It is highly important for the stability of cell membrane also involved in most of the cell functions and importantly for preserving the memory and cognitive functions.

Tembetarine – The alkaloid has enormous potential in the medicinal world producing strong antibacterial, antifungal and cytotoxic effect toward tumor and cancer cells. It is claimed to have the anti-depressant role.

Magnoflorine – The alkaloid displays large physiologic effects regarding its anti-inflammatory, anticancer, suppression of induction phase immune response. Besides it plays a role in HDL oxidation and decreases the arterial blood pressure also possibly induces hypothermia. Magnoflorine inhibits the enzyme α – glucosidase thus having potential effect on diabetes. It is also an anxiolytic drug. The compound has strong effect on memory function possibly by the inhibiting the acetylcholine esterase. Magnoflorine also shows actions toward Muscarinic and Serotonergic receptors. It is the reason why for its major effects on CNS. It has the ability to regenerate peripheral neurons and enables to accelerate remyelination of unmyelinated or damaged nerve cells. The compound enhances the viability of neurons within hippocampus.

Jatrorrhzine – The compound shows anti-inflammatory, anti-microbial and antifungal property. It improves the blood flow also acts as non-competitive MAO – A & B inhibitor.

Aporphine alkaloids – Those compounds exist in two enantiomeric forms, (R) – Aporphine and (S) – Aporphines which belong to the class of quinoline alkaloids. A large number of derivatives / analogs are isolated showing considerable physiologic effects. Those compounds usually have anti-parasite, anti-malarial, antiviral activity possibly by DNA intercalating role also adding inhibitory effect on Topoisomerase. It has strong cytotoxic action on several cancer cells. As per further actions, it blocks LDL oxidation thus preventing the incidence of Atherosclerosis. (R) – Aporphine acts as an antagonist to Dopamine receptor D1 and D2. A few of its derivatives exhibit anti-psychotic and anti-nociceptive effect while interacting with the Dopamine receptor in brain or CNS.

Diterpene furano lactones: The identified ones are Columbin, Isocolumbin, Tinosporine and Tinosporide which are presumably distributed throughout the plant.

Isocolumbin – It shows strong anti-diabetic role which is possibly due to the impact of anti-oxidant action.

Columbin – It shows anti-venom action which is due to the inhibition of Phospholipase A₂ catalyzed hydrolysis of RBC. Further, its anti-parasite or anti-microbial action has been caused owing to the inhibition of cholesterol uptake in Trypanosomes thereby preventing steroid synthesis inside the parasites.

Tinosporin – Despite its numerous virtues and as a potential anti-neoplastic behavior it is a strong teratogen.

Syringin – It is glycosylated phenyl propenoid having numerous physiologic role. It has anti-allergic property due to its immune-modulatory action. Further it acts as anti-inflammatory, anti-nociceptive agent. It has also neuroprotective role by inhibiting Amyloid β (25 – 35) peptide induced neuronal cell death. Further it prevents apoptosis of neuronal cells decreasing Caspase – 3 activity and its expression. As per its added virtues, it is strong antidiabetic also shows anti-ulcer effect.

Steroids: Among the steroids, the major identifiable ones are Ecdysone, Hydroxy – ecdysone, Giloinsterol and β – sitosterol.

Ecdysone – The steroid, Ecdysone or its immediate metabolite 20 – hydroxy-Ecdysone is synthesized mostly inside the non-mammalian species or insects controlling reproduction and molting event. Interestingly, Ecdysone and its active metabolites are seen also being synthesized within few plants (~ 6 % of the plant kingdom) at significantly high levels. This phyto-steroid has considerable pharmacological significances especially designing of safe insecticides, since it has no toxic effects on humans. As an added factor, it has beneficial effects on health. Although no specific receptor(s) are identified in human but studies indicate that it probably interacts with the nuclear receptor allowing its dimerization for respective intracellular functions. Currently the cloning event of its receptor is introduced for gene induction within the mammalian cell system to conduct any necessary gene therapy. By itself, the steroid induces Acetylcholinesterase and Glutamic decarboxylase expression (25 – 30 %) which provides protective effects against several neuro toxins. Additionally, the compound shows anti-diabetic effect by its actions on phosphoenolpyruvate carboxy-kinase plus glucose – 6 phosphatase also inducing Akt phosphorylation within the hepatic cells and exerting anti-obesity function due to Adiponectin secretion on Adipocytes in humans or mammals. It also helps lowering lipid peroxidation thereby enhancing the cardiovascular health. Regarding its role on skin, it helps Keratinocyte generation thus helping the event of wound healing.

Makisterone – It has several identical behavior like ecdysone direction directing molting event, metamorphosis and reproductive behavior of several insects but without exerting any adversarial role in humans.

β – Sitosterol – It is another phytosterols which has been identified within various plants of different categories. It has numerous beneficial effects on human health. Primarily, it acts as a precursor to synthesize anabolic steroids within mammalians including humans. As per further favorable actions, it reduces / prevents the growth of benign prostate hyperplasia (BPH) and enables to lower the plasma cholesterol in circulation.

Miscellaneous components 

Pharmacological effects: It is necessary to discuss several of the pharmacological effects which are immensely beneficial for health.

Antidiabetic effect – T cordifolia, particularly the stem has been in use for a long time to control diabetes. The plant is superbly effective in controlling the disease. It has been identified that the alkaloid fractions having Magnoflorine, Palmatine, Jatrorrhzine are majorly responsible. The presence of tannins, cardiac glycosides, flavonoids and steroids also partially contributed in this act. The ethyl acetate, Chloroform and dichloromethane extract of stem can inhibit salivary amylase and glucosidase exerting effects on post-prandial glucose level.

Immunomodulatory effect – These compounds identified in T cordifolia are widely known for the immune-modulatory responses. They are further responsible for the cytotoxic actions. Those improve phagocytic actions of macrophages enhancing NO production by stimulating splenocytes also generating the ROS in neutrophils.

Anti-HIV actions – The extract of root shows several phytochemicals that can decrease the recurrent resistance of HIV virus enhancing the therapeutic effort. The components listed in the ‘Miscellaneous’ category in the table is seen to act as protease inhibitors for HIV and drug resistant HIV.

Anti-arthritic and anti-osteoporotic effects – The plant is widely known as a traditional medicine for rheumatoid arthritis treatment. T cordifolia has effects on the proliferation, differentiation, mineralization of bone matrix of osteoblasts confirmed by the experiments. The ethanolic extract stimulates growth of osteoblasts enhancing the differentiation of cells of osteoblast lineage by enhancing the mineralization process of bones. Ecdysone in T cordifolia shows anabolic and anti-osteoporotic effect. The steroid synthesized within the plant is seen also to induce considerable enhancement of joint cartilages. It causes osteogenic differentiation of mesenchymal stem cells when experimented in mice. In a way it may provide relief to osteoporosis and osteoarthritic affected patients.

Anti-microbial effects – The alcoholic extract shows anti-microbial actions against E coli, Staph aureus, Klebsiella pneumonia, Proteus vulgaris, Salmonella typhi, Pseudomonas aeruginosa, Enterobactor aerogene and Serratia marcesenses. In animal experiments T cordifolia extract works as functionary for bacterial clearance also improving phagocytic properties plus intracellular bactericidal capacities for the neutrophils. It is already confirmed that the extract has potent immunomodulatory role enhancing the phagocytic actions of PMN cells.

Anti-cancer effects – The alcoholic extract particularly from the root shows anti-cancer activities. The extract also provides radio-protective effect indicated due to the enhancement of body weight, tissue weigh and tubular diameter. Extraction by CH₂Cl₂ exerts potent cytotoxic effects in cancer cells. The effect is more pronounced than the chemotherapeutic drug, Doxorubicin. Some of the diterpene lactones are potent in that act and identified to be the underlying cause. The cells undergo apoptosis after being blocked at G1 phase owing to the expression of per-apoptotic gene, B_ax while decreasing the anti-apoptotic gene, B_cl – 2 expression. In vivo anti-angiogenic activity of B16-F10 melanoma has been detected by the increment of pro-inflammatory cytokines that includes IL-1β, IL – 6, TNF – α and anti-angiogenic agent IL – 2 also the tissue inhibitor of metalloprotease -1. The poly-saccharide fraction of T cordifolia can reduce the metastatic potential of melanoma cells, B16 –F10.

Anti-oxidant role – The alcoholic extract exhibits anti-oxidant properties if orally administered. It increased erythrocyte membrane lipid peroxide and catalase activities. The extract contains inhibitors of anti-oxidants and aldose reductase therefore it lowers the chemotoxicity caused by the free radicals. It possesses strong free radical scavenging ability while interacting with superoxide anion (: O^-2), hydroxyl radical (●OH), nitric oxide radical (●NO) and peroxynitrite (●ONOO^–). The extract from leaf has α – glucosidase inhibitor identified as Saponarin (Flavone glucoside, Isovitexin – 7 – O – glucoside) which also shows considerable hepato-protective and anti-oxidant action. Additionally, the alkaloid fraction of extract exhibits strong protection against aflatoxin induced nephrotoxicity. The extract also shows radio-protective action against sub-lethal dose of γ – radiation on the experimental mice.

Male anti-fertility effect – In experimental rats, oral administration of alcoholic extract of T cordifolia stem is seen to reduce sperm motility as well as the density. Simultaneously, it lowers the level of serum testosterone, protein, sialic acid and glycogen. In addition, it depletes the vesicular fructose content in testes. All these events cause reduction of fertility in male rats.

Hypolipidemic effect – The aqueous or alcoholic extract can lower the cholesterol, lipid, LDL and VLDL in the circulation of both diabetic induced and non-diabetic laboratory rats. The effect is somewhat less than any of the commercial statin drugs.

Anti-depressant effect – The herb exhibits potent anti-depressant effect along with improving the cognition and memory within brain. The process involved is preventing of reuptake of vasoactive amines which leads to the enhancement of norepinephrine, serotonin and dopamine as well as decreasing the level of GABA within the brain that have been noticed during its use. The enhancement is caused further due to the less degradation of those amines for the action of herb as MAO inhibitor. Additionally, the antagonism of GABA_B receptor and its associated G-protein signaling is identified to be an added mechanism in this context. The role of anti-oxidant also plays an important part in this protective function thereby improving the memory and cognitive function and mental concentration. The herb prevents cerebral ischemia also helps improving the CNS tissues suffering from any ischemic injury. T cordifolia is uniquely helpful in controlling depression, attention deficit disorders and Alzheimer’s disorder. The intact herb or its extract is considered to be a good psycho-pharmacological agent.

Anti-complement effect – The anti-complement action is known being a part of immunomodulatory effect and the designated components are already shown. In typical experiments, the identified components, Syringin and Cordiol prevent immuno-hemolysis of antibody coated ship erythrocytes by the guinea pig serum. The event of reduced hemolysis occurs due to the inhibition of C3-convertase acting in classic complement activating pathway. The compounds also enhances the IgG antibodies in serum. Interestingly, at high doses the effect is seen to be leveled off. Whereas the macrophage activation is noticed for Cordioside, Cordiofoliside A which is in increasing mode following the increment of concentration.

Conclusion: Undoubtedly, Tinospora cordifolia shows huge medicinal potential. It has been noticed that the level of the ingredients synthesized within often vary regionally. Expectedly, its medicinal efficiency will also vary accordingly. Further the isolation of numerous phytochemicals and its subsequent applications in medicine at recent days makes this herb a treasure trove in herbal chemistry.

Costus speciosus / Crepe ginger /কেঁউ / কেমুক / কেতকী।

General features: It is a perennial rhizomatous succulent flowering plant belonging to Costaceae / Zingiberaceae family. It has been placed in the genus of ‘Costus’ by the famed Swedish botanist Karl Linnaeus in 1753. The name Costus speciosus was actually offered by him. Prior to this naming, it was recognized as Hellenia following the name of Finnish botanist Karl Nicolas von Hellens. The plant has the uncanny similarity with ginger (Zingiber) in its appearance except having a row of spiral leaves in its frame. In English it is named Costus speciosus (C speciosus) or Crepe ginger. In Hindi it is known as Keukand whereas in Bengali, it is called Keu` / Kemuk / Ketaki (কেঁউ / কেমুক / কেতকী). The plant is a native of South East Asia thus tends to grow in the warm tropical or sub-tropical climate. Besides India, Indonesia, China and adjoining areas, it also grows in Australia (Queensland), Mauritius, Fiji, Hawaii, Costa Rica, Belize, West Indies, Micronesia, Melanesia and New Guinea. In most Western countries, it is cultivated for the ornamental reason whereas in Southeast Asian nations it is grown for the medicinal and herbal needs due to its immense beneficial role on health. The herb grows nearly 9 ft high from the horizontally spread rhizomes which are covered with sheaths at the lower end. The leaves are thick elliptical or oblong or oblong- lanceolate and arranged spirally. They are 8 – 14 inches long and 2.5 – 4 inches wide having silky underneath. The flowers are large white cone with spiked terminal having red bracts with yellowish throat. The tiny fruits are globular and trigonous and red capsules and 0.5-inch diameter. The seeds are black with white aril. The flowering occurs just after the rainy season, starting from the month of October to end of December. The rhizomes are either straight or slightly curved and cylindrical, 4 – 15 inches in length with 1.5 – 2.5 inches diameter. The plant grows from the seeds dispersed by birds after eating the small fruits. It has been used in folk medicine for treating asthma, rheumatism, diabetes, hepatic disorders and many fungal diseases. The plant is extensively cultivated since 1920 at the high altitude of Himachal Pradesh, Kashmir and Uttarakhand, particularly in the northern hill states of India. It is considered as green gold becoming an important income source of the local farmers. In Northern India, it is known as Kuth roots. The state governments of those regions encourage its higher production output. There is a large demand for the Kuth oil. The herbal industries in India and abroad are the major consumers. The annual production in India is ~10,000 kilograms a year and a major portion of it is exported to Europe, Japan and Middle East countries. Since the oil is an expensive item so adulteration in most of the commercially available products is very common.

History: As per the history, C speciosus is known from the ancient times in many parts of the world especially within Indian subcontinent and Mediterranean regions. The dried roots were used as incense out of eleven ingredients of Saussuria, mentioned in the Hebrew religious book, Talmud. The Greeks and Romans used it as perfume and spice, which was also mentioned by the famous Greek philosopher and botanist Theophrastus in ~ 400 B.C. As per the further history, it has been revealed that the Hellenist King Seleucus Callinicus around 250 B.C. imported it from India as a gift to the Milesian King for medicinal use. The elder Pliny, the famous Roman scientist (23 – 79 AD) identified two varieties of Costus, white and black. The white variety is noticed to be more fragrant and named as Costus speciosus. Since then its dried root is used as incense. It is one of the common members of spice exported to the ancient Rome. In Arabic, it is called Qust which was used as a medicine at the time of Prophet Mohammed particularly during the post-menstrual wash for women. The oil extracted from dried roots after mixing with olive oil was applied to treat Alopecia and Chloasma (formation of dark coloration on skin). The root extract was traditionally used to treat toothache, headache, skin diseases like ring worm, asthma, dysentery and rheumatic problems. The legend tells that even the Prophet once said that “If someone’s child gets ‘Azra’ (meaning headache in ancient Arabic language) then mother should grind Qust in water and apply to the child”. In Islamic medicine C speciosus was frequently recommended to treat pharyngitis, tonsillitis among the children also curing pleurisy or to use as an antidote in case of snake bite. In Islamic world it is perhaps one of most effective folk medicines.

Traditional / folk uses: The rhizomes and roots are the most usable parts of this plant for major medicinal needs. They are bitter and astringent by taste. Experiences indicate that they have been traditionally in use for anthelmintic, febrifuge, depurative, purgative, expectorant, toxin removal, and aphrodisiac, tonic or stimulant purposes. The recent pharmacological studies make further addition to the list like anti-hyperglycemic, antifungal, antioxidant, anti-inflammatory, antibacterial, anti-cholinesterase action, diuretic, larvicidal, anti-stress and estrogenic. It also has anti-spasmodic and anti-fertility actions particularly those are grown in Indo-china or Indonesia. As a folk medicine practiced in many areas of the world, it has been further used to treat dropsy, pneumonia, jaundice, mental problems and urinary problems. Leaf prepared from leaves are commonly used as a febrifuge. It has several other identical roles like the rhizome. It is claimed to cure leprosy and possesses anti-vermin effect in addition to its anti-inflammatory, cardiotonic and anti-depressing role on CNS.

Use of Costas speciosus root oil: The oil extracted from C speciosus roots has light yellow or brownish color having weird smell. Although no detailed studies are performed but it shows several of its benefits. The oil has strong larvicidal role on mosquito larvae. In addition, it provides potent insecticidal effects. The compounds that are majorly responsible are Dehydro-costus lactone and Costunolide. These compounds either individually or as a mixture in root oil exhibit powerful anti-inflammatory actions. Studies further indicate that the oil also has potent anti-cancer action particularly on the breast cancer. Further, the oil offers calming effect during the stress, inhaling it during the child birth reduces pain and anxiety among women. Owing to its somewhat unpleasant odor it is mixed with the other pleasant smelling essential oils as flavoring agent for inhaling use.

Chemical constituents and biological role: The major identifiable phyto compounds synthesized within rhizomes and leaves are alkaloids, steroids, glycosides, phenolics, flavonoids, tannins and β – carotenes. The plant also reserves appreciable amount of fatty acids and oil especially in seeds and rhizomes. The composition is Palmitic – 56 %, Stearic – 8.5 %, Oleic – 23 %, Linoleic – 7 % and Arachidic – 2 %. The notable phyto-chemicals isolated from the plant are Diosgenin, β – sitosterol, Furostanol saponins, Saponins-costuscosides, β – D-glucoside, Prospagenins, Dioscin, Gracillin, Di-hydro-phytylplastoquinone and α – tocopherol quinone. A large varieties of steroids and saponins are found in the leaves, stems and rhizomes of C speciosus. The major constituents are Diosgenin. Its highest level is in the flower (1.21 %) and next is the stem (0.65 %) whereas the leaves have the least (0.37 %). The other steroidal constituents are Tigogenin, Dioscin, and Gracillin, Furastanol and β – Sitosterol and its glucosides.

In addition to those, a large number of other bioactive phytochemicals are identified in the plant eg, β – amyrin, Camphene, Costunolide, α – Humelene, Lupeol and Zerumbone. The majority of them have anti-cancer / anti-proliferative properties when studied both in vivo and in vitro. For example, Diosgenin is a phyto-steroid that has anticancer, cardio-protective, anti-diabetic, neuro-protective, immune-modulatory, skin-protective, anti-inflammatory and estrogenic role. Additionally, it can also inhibit lipid peroxidation. Furastanol which is a saponin, inhibits COX – 2 generation causing anti-inflammatory effect also exhibiting anti-proliferative actions on several cancer cells.

Papaverine is an opium alkaloid but synthesized in it also. The compound is often used to treat erectile dysfunction. In addition, it exhibits strong analgesic and anti-spasmodic effects. It is an inhibitor of phosphodiesterase – 4 & 10. The later type resides only in the brain. Tigogenin is a steroidal saponin that can prevent osteoporosis and shows potent anti-diabetic properties. Dioscin is also a steroidal saponin. It induces apoptosis in cancer cells including hepatic and pancreatic carcinoma. Gracillin, another steroidal saponin has powerful anticancer property. β – Sitosterol, widely known phyto-sterol is the precursor of various anabolic steroids. It has a role in reducing blood cholesterol and used in treating benign prostate hyperplasia (BPH). Zerumbone which is a sesquiterpenoid cyclic ketone synthesized in the plant by the oxidation of α – Humulene catalyzed by the enzyme, Zerumbone synthase using NAD⁺. This sesquiterpene shows strong anti-oxidant, anti-inflammatory and anticancer property. β – Amyrin imposes anti-inflammatory and antinociceptive effect. The persistent nociception occurs due to the activation of cannabinoid receptors (CB1 & CB2) also owing to the inhibition of generations of cytokines, NF – κβ, CREB and COX – 2. Another well-known pentacyclic triterpenoid Lupeol also plays a series of biological role. It acts as anti-inflammatory, anti-microbial, anti-proliferative, anti-invasive, anti-diabetic, anti-angiogenic and cholesterol reducing agent. It can also efficiently heal wound, helps lowering cardio-vascular and kidney diseases along with rheumatic arthritis. Costunolide is the other sesquiterpene lactone that shows numerous physiological effects as an anticancer, anti-inflammatory, anti-viral, anti-mycobacterial agent. Additionally, it shows potent inhibitory action on telomerase action and exerts apoptosis on numerous human tumor cell lines.

Pharmacological role:  The folk use of C speciosus deserves mechanistic interpretations that compels to search for its pharmacological effect in health. Interestingly, it has been noted that ways of extractions make large differences regarding the degree of pharmacological / medicinal actions reported in frequent instances, since extractable molecules differ in solubility towards the solvents owing to its polarity variation. Below is the few pharmacological role of C speciosus.

Anti-oxidant effect –   Phenolics, flavonoids and several others within C speciosus provide protections against the hazardous role of naturally generated ROS by scavenging or chelating the metal ions involved during the adversarial role. The methanolic, ethanolic and chloroform extracts of roots, leaves, stems and segments of rhizomes of C speciosus indicate great antioxidant effect, particularly, if extracted by using the methanol. The high solubility of glycosides, tri-terpenoids, flavonoids, tannins and steroids are considered to be responsible for antioxidant role, noticed also in the vivo studies. The majority of underlying components are identified. Each one individually shows the anti-oxidant property but no synergism is yet recorded for the mix. The effect is only seen as additive.

Anti-diabetic action – The anti-diabetic role of C speciosus is impressive as well as multifaceted. The effect has been identified to be due to the presence of Costunolide and other sesquiterpene lactones. Among them Costunolide is noticed to be the most prominent one. The compound(s) stimulates pancreatic β – cells helping secrete Insulin subsequently inhibiting the expression of NOS thereby assisting to regenerate the β – cells also. The oral administration of crude C speciosus extract to Streptozotocin (STZ) induced diabetic rats is seen to normalize the plasma Insulin and C-peptide levels. Additionally, the expression of Insulin, Insulin receptor, Glucokinase, Pyruvate kinase and Succinate dehydrogenase and glucose transporting protein are also promoted. The effect is somewhat comparable to Glibenclamide treated animals.

Further the extract shows inhibitory effect on α – amylase and α – glucosidase enzymes expectedly delaying carbohydrate digestion and subsequent glucose absorption in the body. In that way, the event lowers the post-prandial elevation of blood glucose therefore decreasing the glycation of plasma proteins which is considered beneficial for health.

As per additional assistance, the extract helps expression of intestinal monosaccharide transporter genes and gluconeogenic enzymes also furthering the ability to regenerate β – cells of pancreas for maintaining the normoglycemic effect.

Anti- cancer effect – The anti-cancer effect of chemo-therapeutic agents is normally exerted through cytotoxicity by attacking the specific molecular targets involved in the growth of cancers. The identifiable components are cyclic sesquiterpene lactones. Amon those Costunolide is seen highly effective thus used as regular medication in the cancer therapy. Costunolide arrests the cell cycle at G2/M phase of human breast carcinoma, MDA-MB-231 and MCF – 7 cell lines by altering the expression of cell cycle regulators (Cyclin D1, D3, and CDK – 4 & 6 and others). It downregulates the over expression of NF – κβ subunits p65, 52 and 100 in those cells. The compound enables to lower the viability by inducing apoptosis (IC₅₀ ~ 40 µg) by activating Caspase – 3 and Caspase – 9). The other active component Diosgenin shows similar apoptotic role when tested on hepatocellular carcinoma, HepG2 cells (IC₅₀ ~ 32 µg / ml). It is much active (IC₅₀ ~ 11µg / ml) than Costunolide in the case of MCF-7 cell lines. Additionally, it increases the level of death receptor – 4 (DR4) and Caspase – 3. Interestingly, C speciosus shows no adverse effects on normal cells.

Anti-inflammatory effect – Scores of studies regarding the inflammatory role of C speciosus have been reported following the traditional uses at past and present. The recent scientific assessment by numerous laboratory investigations further confirms the fact that C speciosus is considerably effective in treating inflammation, rheumatism, fever and bronchitis. Once again, the most potent compound identified is Costunolide which attenuates the effect of TNF – α, IL, IL-6, iNOS and COX – 2 through the inhibition of NF – κβ and mitogen activated protein kinase pathways. The n- hexane – chloroform soluble matters of methanolic extract of rhizome shows several powerful biological compounds eg, 22, 23 – dihydro-spinasterone, Dehydro costus lactone, Stigmasterol, Arbusculin –A, Santamarine, and Reynosin.  They considerably reduce the production level of IL-1 β, IL – 6, TNF – α, PGE2, LOX – 5 and COX – 2. These effects signify that the plant is superbly effective in regulating any inflammatory diseases which has been established by using both in vivo and in vitro models. Most of the sesquiterpene lactones provide good anti-inflammatory effect and additionally the presence of sterols synergize it further.

Hypolipidemic effect – In this context, the active compound exerting Hypolipidemic effect is also Costunolide. The incidence of hyperlipidemia causing high concentration of lipid in circulation occurs largely within the diabetic patients, primarily due to the deficiency of Insulin. Under the deficient situation, fatty acids liberated from the adipose tissue accumulates in plasma causing hyperlipidemia. It is noticed that Costunolide can significantly decrease the total serum cholesterol, LDL – cholesterol and triglycerides. Simultaneously, serum insulin and HDL – cholesterol levels are substantially enhanced. The effect is due to the stimulated secretion of Insulin from β – cells by Costunolide while inhibiting the expression of NOS. Identical behavior is noticed by Eremanthin, another sesquiterpene lactone from C speciosus. In addition, other components of C speciosus impose different effects regarding lipid digestibility by enhancing the expression of fatty acid transporter gene within intestinal cells.

Hepato-protective effect – The rise of marker enzyme levels in plasma, like Aspartate amino-transferase (AST), Alanine aminotransferase (ALT), Lactate dehydrogenase (LDH), Alkaline phosphatase (ALP), Acid phosphatase (ACP) including the bile pigment, Bilirubin due to the leakage from liver indicates hepatic disorders under any circumstances. The oral administration of C speciosus extract brings that to the normal level. The effect is seemingly better than the drug Silymarin (a racemic mixture of Silibinin-A & B) widely known plant flavonoids, available commercially. Numerous studies have convinced that C speciosus enables to protect liver from the inflammation and injuries by drugs or any toxic products.

Anti-microbial effect – The extract of leaves and rhizomes exhibits antibacterial and antifungal actions. It is also seen effective against several viral infections like influenza, viral hepatitis and human immune-deficiency viruses.

Adaptogenic actions – The function of an adaptogen is to exhibit anti-depressive, anxiolytic, nootropic and anti-fatigue also CNS stimulating actions in brain. In this context, the mechanism involved regarding the extract of C speciosus is noticed to reduce the stress induced rise of Serotonin (5 – hydroxy tryptamine) and 5 – Hydroxy Indole acetic acid (5-HIAA) within brain neurons which prevents the alarm system by provoking the increment. In that way, the extract possibly exerts the anti-depressant effect. Additionally, as per its other folk use, C speciosus is successfully used against the headaches. The underlying mechanism or any particular active ingredients is still left unknown.

Antispasmodic and erectile function effect – The presence of alkaloid, Papaverine is identified to be the liable factor for those actions. The extract lowers vaso-spasm and helps penile erection by allowing the blood flow to the organ thus acts as a smooth muscle relaxant while also behaving as an inhibitor of Phosphodiesterase – 4 & 10 A inhibitor, causing the rise of intracellular cAMP level. It also has direct effect on the Calcium channel. It also acts an anti-psychotic drug.

Anti-acetylcholinesterase effect – The extract has anti-acetylcholinesterase property although no specific alkaloids or others have been identified yet. The extract is therefore used for treating Glaucoma. It also helps patients suffering from Parkinson or Myasthenia gravis and rapid eye movement sleep within autistic children.

Toxicological effect – No specific data is so far available regarding the use of any parts of C speciosus. Versatile tests on laboratory animals even at a high dose of extract (~ 1200 mg / Kg / day) on Wistar rats or mice for 3 months exhibits no significant level of toxicity in any organs except the lowering of cholesterol and glucose levels in plasma.

 

Cordia dichotoma / Indian cherry / Clammy cherry / Gunda /শেলুকা / বুহাল / বহুবারা।

General features: The plant grows in moist tropical or subtropical regions of South and South East Asia, Papua New Guinea, Australia and other temperate zones which causes size variations concerning the plants, fruits and leaves. The botanical name is Cordia dichotoma (C dichotoma) but in English it is called Clammy cherry or Indian cherry. In Hindi it is named ‘Gunda’ whereas in Bengali it bears several names like ‘শেলুকা / বুহাল / বহুবারা।‘. The plant belongs to Borganaceae family. It is a deciduous tree which usually grows 10 – 16 ft tall and 4 – 5 ft wide. Some of the species can even grow further attaining ~ 70 ft high and 10 – 15 ft diameter bole. The stem bark is quite smooth and greyish brown. The unripe fruits are globular in shape, about 0.5 inch diameter with shining green or pinkish yellow that turns black on ripening. The flowers are short trailed, bisexual by nature and white in color that blooms at night. Flowering takes place from March and lasts until May when new leaves appear. Whereas the fruits ripen within June to August. The leaves are elliptical – lanceolate to broad ovate with round base which are also slightly dentate. The plant is considered being the native of Indian subcontinent, Indochina, Myanmar, Malaysia, Australia and Japan. In India it grows almost everywhere even in the dry climate of Rajasthan. The green fruits are pickled and frequently eaten with salads or with Chapatis as vegetable. The leaves are normally fed to the cattle. The tree as a whole has huge medicinal benefits. In rural India it is frequently used for anti-bacterial, anti-viral and antitussive uses. The folk uses of fruits are directed to treat common cold, fever, dyspepsia, cough, respiratory distress and catarrh. The stem bark can cure diarrhea, leprosy, gonorrhea and burning sensation during urination. Additionally, it also has numerous other medicinal and nutritional effects. About 300 species exist within the Cordia genus. Interestingly, all of them exhibit biological or physiological effects. Some even displays antifungal, larvicidal and anti-bacterial actions in addition to other health benefits preventing or curing various diseases and disorders. In Rajasthan and Western Ghats, the fresh flowers smashed in plain yogurts are often spread over the body for protecting against drastic heat and sun.

Nutritional and other aspects: The unripe green fruits are usually used for making pickle while preserving in spiced oil and lemon juice which is often eaten with salad or any cooked vegetables and Chapattis, the practice is popular in Indian dinner. In most occasions the ripen fruits are consumed to enjoy its sweet and astringent taste. The fruits have therapeutic values against diabetes especially owing to its Chromium content (0.2 mg / 100 g). The grinded seeds enriched with oils and proteins are consumed for the cattle food. The gum exuded from C dichotoma containing 97 % polysaccharide is used for the pharmaceutical needs. The plant also produces natural cellulose that can be woven for making the fabrics. Table shows the nutritional content of leaves, seeds and fruits.

Plant part	Nutritional component ( / 100 g)
Leaves	15 % protein,  27 % crude fibers,  52 % Nitrogen free extract, ~17 % Ash, 4 % Ca, 0.3 % Phosphorous.
Seeds	32 g water, 46 % oil, 31 % protein.
Fruits	6 g water, 35 g protein, 37 g fat, 18 g carbohydrate, Ca – 55mg, P – 275 mg, Zn – 2mg, Fe – 6mg, Mn – 2mg, Cr – 0.2 mg, Cu – 1.6 mg.

Folk medicinal use:  The plant has been known for ages due its large potential to treat numerous health problems which has been already introduced in the Ayurveda. It is also included in the Mediterranean Unani medicine of Persian and Arabic nations. The bark extract is commonly used to treat dyspepsia. Often it is mixed with pomegranate to control the dysentry. But to minimize the colic pain the extract is often mixed with coconut water. The leaves, fruits, bark and seeds exhibit anti-diabetic, anti-inflammatory, analgesic and immune modulating properties. The fruit extract or syrup made from it are used to treat following health problems: 1) Fever, 2) Cough, 3) Worm infestations, 4) Blood & bleeding disorders, 5) Seminal problems (untimely or less ejaculation volume) and 6) Asthma. The fruits are heavily enriched with medicinal components. Like fruits, the bark extract is used for treating; 1) Blood disorders, 2) Wounds, 3) Digestive help, 4) Small pox, 5) colic due to intestinal worms, 6) Leprosy, 7) spider bite, 8) Blisters and 9) ulcers. In Mediterranean regions like in Egypt, dried fruits are sold in the market as Sapistan which are used as Unani medicine. The dried fruits have effects on chronic bronchitis, influenza and also acts as laxative.

Chemical components: The major phyto-components identified in leaves, fruits, seeds and barks fall into the categories of pyrrolizidine alkaloids, coumarins, flavonoids, saponins, terpenes and sterols.

Seeds – Betulin, α – amyrin, octasanol, Lupeol – 3-rhamnoside, β – sitosterol, β – sitosterol – 3 – glucoside, hentricontanol, hentriacontane, taxifolin – 3 – 5-di-rhamnoside, hespiritin – 7 – Rhamnoside and fatty acids (palmitic, stearic, arachidic, behenic, oleic, linoleic acid). Few flavonoid glycosides (robinin, rutin, rutoside, datiscoside and hesperidin) and a flavonoid glycone (dihydro-robinatin) and 2 phenolic derivatives (chlorogenic and Caffeic acids).

Major chemical components from seeds

Bark –  Allantoin, β – sitosterol, 3`- 5-di-hydroxy-4`-methoxy flavanone – 7 – O – α – rhamnopyranoside and gallic acid.

Fruits & leaves – Pyrrolizidine alkaloids like Macrophylline, coumarins, flavonoids, terpenes and sterols like β – sitosterol. Further fruits also produce arabino-glucan, D- glucose and L-arabinose. They also contain quercetin and quercitrin.

A large majorities of the similar compounds have been usually identified throughout the plant.

Pharmacological properties: The pharmacological role of extracts of plant parts are studied in the laboratory and some of the corresponding active components are subsequently identified. For example, the ethanolic extract of bark shows significant antibacterial and antifungal actions. It is active against Gram negative bacteria like E coli, P aeruginosa and Staph aureus. The antifungal effect is studied and confirmed against Aspergillus Niger, Aspergillus clavatus and Candida albicans, the pathogenic fungi. The antibacterial effect is comparable to ampicillin, ciprofloxacin, norfloxacin and chloramphenicol whereas the antifungal action is closely similar to Nystatin and Griseofulvin. Recent discoveries indicate that naturally occurring flavonoids could be immensely responsible for the antibacterial and antifungal actions. The mechanism behind the effects are due to several reasons, inhibition of nucleic acid synthesis, cytoplasmic membrane function, energy metabolism, preventing biofilm formation, inhibiting porin action on cell membrane, altering membrane permeability and reducing the pathogenicity. The other important component in bark extract is Allantoin which is often used in the cosmetics for moisturizing and keratolytic effect. It also has medicinal effects in producing wound healing, exerting soothing effect and anti-irritant effect. It is a good skin protectant also acts an inflammatory modulator. Allantoin helps fibroblast proliferation and often used as desquamation of upper dead skin layers. In case of atopic dermatitis, instead of steroids, Allantoin is applied also. The presence of β – sitosterol in appreciable level makes the extract medicinally important. The compound exhibits enormous physiological role acting against allergies, inflammation, asthma, bronchitis, and rheumatic arthritis, also lowering plasma cholesterol preventing heart diseases, prostate and colon cancers, benign prostate hyperplasia and relieving pain, boosting immune system and enhancing sexual function. The extract of fruits and leaves have strong antioxidant role due to the presence of flavonoids, saponins, coumarins and others. But the potent antimicrobial properties is noticed in leaf extract due to the presence of Macrophylline which is a pyrrolizidine alkaloid.

Concerning coumarin and its derivatives, they have enormous medicinal uses. It is usually used as anti-coagulant (Warfarin) and increasing the level of anti-thrombin in plasma also used for treating lymphedema. The compounds exerts uricosuric (helping removing urea from circulation) and antioxidant effect. Coumarins has potent antimicrobial role too. The triterpene Betulin shows strong anti-tumor activity. It enhances insulin sensitivity, lowers obesity, atherosclerosis, lymphatic diseases and tuberculosis and several other health problems. Amyrin has anti-nociceptive and anti-inflammatory effects via the activation of cannabinoid receptors (CB₁ and CB₂) also inhibiting the production of inflammatory cytokines like NF – κβ, COX – 2 and CREB (transcription factor for cAMP binding element). Lupeol is a pentacyclic triterpene, sterol by the nature. Like the others it also exerts considerable physiologic effects. It has anti-inflammatory, anti-microbial, anti-protozoal, anti-proliferative, anti-invasive, anti-angiogenic and cholesterol reducing agent. Studies indicate that Lupeol modulates IL-2, IL-4, IL-5, IL – β, proteases, cFLIP, Bcl-2 and NF-κβ. Taxifolin and its glycosides are potent anti-oxidant also having significant anti-tumor effects on ovarian cancers by inhibiting fatty acid synthase enzymes. It is also useful against methicillin resistant staphylococcus bacteria. The high level of flavonoids and its various glycosides makes this plant very healthy for diet. Besides being anti-oxidant, they are good for cardio-vascular diseases, exert anti-cancer effect, being anti-inflammatory and often anti-bacterial also. The phenolic derivatives like Caffeic acid or Chlorogenic acid have numerous biological effects. For example, Caffeic and Chlorogenic acids have strong anti-oxidant actions and also exhibits anti-inflammatory effect. In addition they can slightly lower the arterial pressure. Caffeic acid on the other hand has immunomodulatory effect and in addition it shows anti-tumor role particularly Fibrosarcoma when studied in vitro using human HT – 1080 cell line.

Medicinal uses: The majority of medicinal uses are followed by viewing the folk practices. The tasty fruits are edible and seen to be effective against colic pain, cough, fever and several diseases of skin also for seminal weakness or sexual disorders. The bark extract is effective against many illnesses due to its large content of Gallic acid and β – sitosterol.

Bark – The extract is used as tonic to prevent colic, dysentery, dyspepsia, chronic diarrhea, strangury and catarrh. It is further used in controlling fever, boil and tumor, and also ulcers in the mouth. Gargling the extract can even strengthen the teeth. It provides relief on itch. Both bark and root extract has strong larvicidal property in addition to fungicidal and destroying several pathogenic parasites due to the presence of meroterpenoid napthaquinones and cordioquinones.

Seeds – The seed extract has potent free radical scavenging property owning to the presence of abundant level of flavonoids like Kaempferol, Quercitin, iso-rhamnetin and Taxifolin. In addition the extract also exhibit strong anti-inflammatory action. The methanolic extract has powerful anti-microbial, anti-fungal and larvicidal effects.

Fruits – The fruits or its extract or mucilage can treat coughs, problems of chest, uterus urethra also acts as laxative. The ripe fruits are sweet and demulscent.

Kernel of fruits – This extract can cure ringworm when applied on the specific areas.

Leaf – The alcoholic extract leaf shows abortifacient effect on female laboratory rats also indicate anti-implantation action thus acting as natural contraceptive. But they are effective in reducing headache and ulcers.

 

Clerodendrum infortunatum / Bhandira / Ghentu (ঘেঁটু)

General features: The botanical name of this perennial shrub is Clerodendrum infortunatum (C infortunatum). The English name offered is ‘Hill glory bower’. In Sanskrit, the plant is known as Bhandira whereas the Bengali name is Ghentu (ঘেঁটু) and in Hindi it is called Bhat. The plant belongs to Lamiaceae family but often categorized within Verbenaceae also. Although growing mostly in the wild but it is traditionally valued for the medicinal properties therefore well-documented in the ancient Indian apothecary (Ayurveda). There are approximately 150 species of Clerodendrum known so far. All of them grow in the tropical climatic condition thus claimed to be the native of South Asia like India, Pakistan, Myanmar, Thailand, Malaysia and Sri Lanka. The plant is a flowering shrub. The hollow stem is 5 – 7 ft high producing hairy leaves on both sides and slightly oval shaped,  2- 8 inches wide and 3 – 9 inches long. Flowers are often white or purple-pink in color. The plant grows from April to August in cluster. They are ~ 4 inches long drooping downward with extended corollas about ~ 2inches in size. The fruit berries turns black when ripe and ½ inch in diameter. Even today, the parts of this plant is used as folk medicine to treat various ailments like, diarrhea, venereal and scrofulous problems, varieties of wounds, post-natal complications, removing ascarids (worms) in anus, laxative, anthelmintic and cholagogue.

History: The name Clerodendrum was awarded by the famous 18^th century Swedish scientist / botanist, Karl Linnaeus. He included the plant in his book “Species Plantarum”, written around 1753. He offered the Greek words ‘Kleros’ signifying fate whereas ‘Dendron’ a tree. He further mentioned about its medicinal potential revealing the origin being native of Asia. Later in 1997, phylogenetic analysis of DNA showed that Clerodendrum is polyphyletic indicating not having common ancestors.

Traditional medicinal uses: The extract of C infortunatum exerts strong diuretic effect. It is also highly effective in treating blenorrhoea (vaginal mucus discharge problem). The sap from leaf exhibits antiseptic action therefore often used for the skin wash in many rural areas. Further, the leaves warmed over hot pots are used as poultice to reduce any swelling of muscle or stomach. In addition, the fresh crushed leaves is also used as a poultice to treat burns, boils, wounds, skin ulcers or skin diseases. The leaf juice is used as herbal bath for the newborn children or children suffering with furuncles (boil). Regarding the root, it acts as diuretic and Galactogogue (enhancing breast milk production). Interestingly, the root extract is a good antidote against Antiaris (cardiac glycoside) poisoning. It is further used to treat dysentery, intestinal infection and kidney malfunction and also often used for curing jaundice. The recent studies on C infortunatum find several more medicinal actions in addition to those known for its folk uses. The plant has anti-hyperglycemic / antidiabetic, anticonvulsant, anti-pyretic, antispasmodic and anti-venom effects.

Chemical compounds: The main phyto-chemicals synthesized inside various plant parts could be characterized in a broad category as, Phenolics, Sterols, Sugars, Flavonoids and saponins.

1. Phenolics – Acetoside, Fumaric acid, Methyl / Ethyl esters of Caffeic acid.
2. Flavonoids – Apigenin, Acacetin, Methyl / Ethyl esters of Acacetin – 7 – O-glucoranide, Cabruvin, Quercetin, Scutellarein, Scutellarein – 7 – O – β – D – glucoranide, Hispidulin.
3. Steroids – Clerodolone, Clerodone, Clerodol and Clerosterol.
4. Terpenoids – Clerodin (saponin diterpenoid)
5. Oil – Glycerides of Lenoleic, Oleic, Stearic and Lignoceric acid.
6. Sugars – Raffinose, Lactose, Maltose, Sucrose, Galactose, Glucose & Fructose.

Several di-terpenes have been isolated from C infortunatum. Isomers of Clerodin are identified among them. Clerodinin A is the predominant one which has potent antifeedant property along with its possession of extreme bitter taste. Oleanic acid has potent hepato-protective actions. It can prevent inflammation, fibrosis and helps rapid recovering of necrosis tissues. It helps amending protein metabolism disorders. It is highly anti-inflammatory, diuretic, immune booster by raising white cells, cardiotonic and anti-diabetic and can prevent growth of murine sarcoma cell line S-180.

Roots – Several triterpenoids and sterols have been identified. Those are mainly Clerodolone, Clerodone, Clerodol and Clerosterol. In addition to these important ones, few sugars like raffinose, lactose, maltose, sucrose, galactose, glucose and fructose are noticed to be present.

Major compounds in root

Flowers – In the case of flowers, the major compounds are, Fumaric acid, Caffeic acid and its esters, β – sitosterol or its glycosides along with few flavones like Apigenin, Acacetin and several of its glycosides.

Major compounds in flowers

Leaves and aerial parts – They are enriched with flavones and sterols eg, Scutellarin, Hispidulin and its glycosides and Stigmasterol and Poriferasterol. Additionally, several Saponins are also present in the leaves.

Major compounds in leaf and aerial parts

Seeds – It contains numerous phyto-sterols and its derivatives eg, 24 – β- ethyl sterol, Clerosterol, 22 – dehydro-Clerosterol, 24-methyl sterol, 24 methyl cholesterol, 24 methyl – 22 – dihydro cholesterol, 24 – β – ethyl – 22-dehydrocholestanol.

Important components in seeds

Medicinal and physiological role: Surprisingly, this wild plant expresses enormous medicinal / physiological effects that are beneficial for health.

Anti-bacterial / anti-fungal actions – The solvent extracts of roots, leaves and stem display considerable inhibition against various bacterial and fungal infections. The major bacteria are Staphylococcus aureus, Salmonella typhi, Kleibsiella pneumonia, and Bacillus megaterium etc and among the fungi are Candida albicans, Aspergillus Niger and others.  The effect of leaf extract is seen somewhat more potent than the roots or stem. Possibly, benzoic acid and its derivatives could be liable for this act.

Analgesic and anticonvulsant effect – The saponin fraction shows potent dose dependent (20 – 100 mg / kg) analgesic and anticonvulsant effects within the laboratory animals.

Anti-oxidant effect – The alcoholic extract made from dry leaves display strong antioxidant effects due to large reserve of various flavonoids which enable to scavenge any generated free radicals (ROS or iNOS) indicated by the in vitro assays.

Anti-inflammatory actions – The alcoholic extract of leaves show considerable anti-inflammatory actions when tested on the laboratory animals. The inhibition is comparable to the non-steroidal anti-inflammatory drug, Phenylbutazone.

Hepato-protective activity – The experiments by inducing liver injury using CCl₄ on the laboratory animals show that plant extract can significantly protect the liver. The level of hepato-protective potential is very identical to Silymarin, having active principle Silibinin – A & B.

Anthelmintic effect – Both aqueous and alcoholic extract of dry leaves or roots show significant anthelmintic property against numerous worms eg, Pheretima posthuma (earth worm) and Raillietina tetragona (tape worm). The identifiable compounds are sterol and flavonoids.

Anti-cancer action – The methanolic extract of C infortunatum was studied in detail bot in vivo and in vitro. In all cases a dose-dependent inhibition of tumor cell volume and increase of life span have been observed. The inhibitory action is due to suppression of lipid peroxidation and enhancing the enzymatic defense systems.

Major chemical contents of C infortunatum and its individual physiologic actions

Compounds	Physiologic effects
Clerodolone	Anti-inflammatory, Anti-pyretic.
Clerodol	Strong anti-inflammatory, Anti-pyretic.
Clerodone	Anti-tumor, Preventing oral cancer, Inhibiting growth of cancer cells.
Clerosterol	Highly cytotoxic to human cancer cells eg, Melanoma and Keratinocytes.
Caffeic acid	Anti-oxidant, Anti-inflammatory, Anti-viral, Anti-neoplastic.
β – Sitosterol	Lowering of plasma cholesterol, Cardio-vascular disease, Preventing colon cancer, Rheumatoid arthritis, Psoriasis, Cervical & Prostate cancer, Lupus, Asthma, Bronchitis, increasing sexual activities.
Apigenin	Anti-inflammatory, Prevent cancers, Neuro-protective, Anxiolytic, Hypoglycemic, Sleep promoting, Bone healing, Anti-obesity and Anti-oxidant.
Acacetin	Anti-inflammatory, Anti-nociceptive, Anti-aromatase, Anti-cancer (inducer of Apoptosis), Effective against dementia, neurological disorders and Alzheimer’s.
Scutellarin	Protective against cerebrovascular and cardiovascular ischemia by cyto-protective actions, alleviating neuronal apoptosis and cognitive impairments, promoting neuronal differentiation, inhibiting oxidative stress, slowing down Alzheimer’s progression.
Hispidulin	Anti-oxidant, Antifungal, Anti-inflammatory, Anti-mutagenic, Anti-neoplastic.
Poriferasterol	Cell membrane stabilizing role, transferring signal during heat shock or any external Stress, Anthelmintic.
Stigmasterol	Helping maintain cell membrane structure, Lowering of LDL and plasma cholesterol, Promising against curing anti-methicillin resistant Staphylococcus aureus.

Sesbania Grandiflora / Vegetable humming bird / Agati / বকফুল।

General features: The botanical name is Sesbania grandiflora (S grandiflora) but commonly called ‘Vegetable hummingbird’ or ‘Agati’ in English. In India, particularly in Bengal the colloquial name is Bok-phul (বকফুল). The plant belongs to the genus of Sesbania and family of Fabaceae. It is a fast-growing plant reaching to 20 – 30 ft high and composed of soft woods. The leaves are 8 -12 inches long grown as leaflets of 10 – 20 pairs. The flowers are oblong 2- 4 inches in length in lax with 2 – 4 flower racemes. They are mostly white but occasionally red, pink and yellow varieties are also available. The pods are slender and straight. They are 12 – 18 inches long holding ~ 30 seeds inside which are 0.3 inch in the sizes. The plant is believed to be the native of South East Asian nations or Northern Australia. The tree has been cultivated in several regions of India including also Sri Lanka requiring largely hot, sunny and humid climate. The flowers of S grandiflora are consumed as vegetable in many South Asian and South East Asian nations eg, Vietnam, Laos, Thailand, Philippine, Java, Sri Lanka, India and Maldives. They are mainly used in making the curries. But besides making curries, the young pods and leaves are also used in the salads. In Bengal, the flowers are eaten by frying in dipping with lentil batter. In Sri Lanka and other Southern Indian states like in Tamilnadu, fresh green pods and leaves are consumed to make curry using coconut gravy. Recently, it is noted that leaf extract enables to inhibit the formation of advanced glycation end-products which presumably is the cause behind several neurological disorders like Alzheimer. The large reserve of linoleic and aspartic acid is thought to be liable for the anti-glycation action.

Mythological viewpoints: It has been described by the Hindu mythology that flower of S grandiflora was appreciated during ancient Vedic period of India by many sages (munis) including the famous personality like Agastya, a great sage and scholar who seems to be the author of many books like Skanda Purana, Varah Purana, Agastya Samhita and several others. According to the legend, he was the pioneer in constructing medicinal aspects of numerous plants in order to treat various ailments inscribed in Atharva Veda, the ancient Indian Medica. His wife, Lopamudra was one of the great philosophers of ancient India. It is also a folk lore that the flowers of Sesbania grandiflora are born at the shining of star, Agastya seen pointing to the north of Sirius. Further the legend says that following the advice of King of the heaven (Devraj) God Indra, Agastya started the practice of medicine using the herbs from the herbal enriched Himalayan region, viewing as the major source. Presumably, the name ‘Agati’ is offered to S grandiflora plant following the Nepali language since Nepal is the country situated on the Himalaya. The countless medicinal virtues of this plant particularly leaves and flowers or even the bark and roots were revealed by the great sage to cure numerous illnesses.

Edible uses: Flowers – They are used either as cooked or raw condition in salads. But it is mostly preferred to make curries or deep fried after dipping in the batter. It is a delicacy in many places of India. The center of the flowers is removed before any use. The flowers of S grandiflora are enriched with sugar and minerals particularly iron. It produces a flavor of mushrooms. The fresh young pods are cooked as vegetable like stews or else used in the salads. The seeds isolated from matured pods are cooked as lentils which are full of proteins. In some Asian nations, the pods are fermented to produce syrup often used in cooking foods.

Folk medicinal uses: In rural India, the young leaves are used for diuretic and aperient actions. The crushed leaves are also used as a poultice for curing sprains, bruises and swellings. It is also applied for rheumatism and itches. Tea prepared from the dried leaves has antibiotic, antitumor and contraceptive properties. The bark extract has astringent taste but exhibits several beneficial effects acting as febrifuge, tonic, anti-pyretic, preventing diarrhea, dysentery, colic or any gastric troubles. In several places of India it is even used in controlling the diabetes. The flower extract is used as emollient, laxative, preventing sinus congestion. In many regions pastes made of young roots are applied to treat rheumatism. It is believed that consumption of flowers can prevent night blindness whereas the juice from fruits would improve the memory. The leaf extract is believed to exert anxiolytic effect.

Phyto-chemicals and actions: Each part of the plant is a rich source of minerals, vitamins and several other beneficial factors.

Leaf – Per 100 g – 8.4 g protein, 1.4 g fat, 2.2 fiber, 1700 mg Ca, 260 mg P, 4.0 mg Fe, 9000 IU vitamin A, 0.21 mg Thiamine, 0.1 g Riboflavin, 9.2 mg Niacin, 270 mg vitamin C, 2005 mg K, 2600 µg β – carotene.

Flower – Per 100 g – 14.5 g protein, 4.0 g fat, 77.3 g carbohydrate, 10.9 g fiber, 145 mg Ca, 300 mg P, 5.5 mg Fe, 291 mg Na, 1400 mg K, 640 µg β – carotene, 1.0 g Thiamine, 0.72 mg Riboflavin, 14.5 mg Niacin, 473 mg vitamin C.

Seed oil – 12.3 % palmitic, 5.2 % stearic, 26.2 % oleic and 53.4 % linoleic acids.

Bioactive components – The major bioactive chemicals identified in the methanolic extract of leaves are: alkaloids, glycosides, steroids, terpenoids and tannins. In addition, there are others like 3, 4, 5-trimethoxy-phenol, erucic acid, 2-furancarboxyladehyde, vitamin E, 4 – methyl-oxazole, palmitic acid, 9 – hexa-decanol and di-octyl esters. The existence of alkaloids have been traced but none have been isolated nor are any structures established. The alcoholic extract of leaves also have high level of Quercitin, Myricetin, and Kaempferol. The other major compounds isolated and identified in roots are the iso-flavonoids like, Isovestitol, Medicarpin, Sativan and the other lupane type triterpene, Betulinic acid.

Besides other organic components belonging to the family of terpenes and flavonoids, a novel protein, SF2 has been isolated from the S grandiflora flower which shows potent anticancer / antitumor actions in course of in vivo and in vitro experimentation by preventing cell proliferation while inducing apoptosis demonstrated by the DNA fragmentation and externalization of phosphatidyl serine in cell lines like colon cancer SW480 or Dalton lymphoma ascites. Presumably, the activation of Caspase 3, 8 and 9, poly ADP – ribose polymerase cleavage along with Cytochrome C release indicates apoptosis inducing cell death. The mechanism involved is the down regulation of apoptotic factors like Bcl-2, p-Akt, COX-2 etc. Advantageously, the protein does not exhibit any toxicity. The protein also shows analgesic and anti-inflammatory actions possibly due to the inhibition of COX-2 generation. Further, the presence of Isovestitol, Medicarpin and Sativan displayed considerable anti-tubercular and antimicrobial property.

Essentially, various tannins, flavonoids steroids and coumarins are identified in all parts of the plant. The majority in the form of saponins are either triterpenes or steroidal by the nature. The very commonly found ingredients are Leucocyanidin and Cyanidines which in largely available within the seeds whereas the flowers majorly synthesize Oleanolic acid or its methyl ester and Kaempferol – 3 – rutenoside. The bark produces large quantities of gum and tannins.

Erucic acid – CH₃ (CH₂)₇ CH = CH (CH₂)₁₁ CO₂H. It is a mono-unsaturated ω – 9 fatty acid. It exists in most of the edible oils (canola, mustard, sunflower, corn etc) in appreciable amounts. It is synthesized by the enzymatic elongation of Oleic acid. It breaks down to shorter fatty acids inside the human liver. Experiments in rats showed that its consumption causes myocardial lipidosis within animals but no such occurrences are ever noticed in the case of human.

3, 4, 5 – tri-methoxy phenol –

The compound, 3, 4, 5-trimethoxy phenol inhibits Tyrosyl-DNA-phosphodiesterase-1 (Tdp1) also takes part in the synthesis of Co-enzymes Q. It is a potential anticancer drug thus widely employed as chemotherapeutic agent. The enzyme, Tdp1 catalyzes the hydrolysis of DNA adducts when covalently linked to the 3` – phosphate of DNA. The inhibitors of Tdp1 targets not only the Topoisomerase -1 but also synergizes with various other commercially available drugs including the inhibitors of Topoisomerase – 2 and other DNA alkylating agents also.

2 – Furancarboxyladehyde / Furfural – 

The compound shows anti-malarial effect. It also acts as antagonists to peroxisome proliferators but agonist toward Estrogen β – receptor pathway.

4- methyl-oxazole –

The compound exhibits numerous physiological role by acting as bronchodilator, anti-asthmatic, kidney and prostate problems. Various oxazole derivatives are widely known for their physiologic role in medicines.

Medicarpin –

Medicarpin stimulates osteoblasts for bone generations also heals several bone defects. Further, it exhibits anti-fungal and anti-parasite activities also enables to prevent cancer cell proliferations.

Betulinic acid –

It is a pentacyclic tri-terpenoid. The compound shows anti-retroviral, anti-inflammatory and anti-malarial properties. Uniquely it exhibits anti-cancer / anti-proliferative effect while inhibiting the enzyme Topoisomerase also activating Caspases, subsequently inducing apoptosis of tumor cells, as evidenced by the fragmentation of DNA.

Oleanolic acid –

It is a pentacyclic triterpene. It exhibits anti-tumor, antiviral, hepato-protective properties. Recent studies indicate that Oleanolic acid can act as anti-HIV and anti-HCV drug. Some of its derivatives work more potently in that regard. It is a powerful anti-inflammatory compound works by inducing Interferon – γ. It also reduces sperm motility as well as the quality thereby causing temporary infertility to the men. Withdrawing it helps regaining the fertility back to the original state.

Flavonoids –

Those are the major flavonoids identified either in free or coupled with the glycosides within different parts of S grandiflora plant. Factually, it has been firmly established that flavonoids are immensely beneficial for maintain good health. They are powerful anti-oxidants. The action mostly relies on its final break down to Uric acid which actually plays the major antioxidant role. Besides this act, these flavonoids inhibit blood coagulation, thrombus formation including the aggregation of platelets thereby reducing the risk of atherosclerosis. They intend to reduce the oxidative stress also its related signaling pathways. As per further benefits, they improve capillary functions, regulate vascular inflammatory mechanisms causing reduction of arterial blood pressure lowering the risk of hypertensions and hyperglycemia including the process of aging.

Pharmacological actions:

Hypoglycemic effect – The antidiabetic effect of flower extract has been confirmed by laboratory experiments using Streptozotocin, Alloxan induced or glucose overloaded animals. The results showed that oral administration of fruit and flower extract restored all the parameters eg, plasma glucose, serum insulin glycosylated hemoglobin, hepatic glycogen, serum marker enzymes aspartate and alanine transaminase, creatinine sulfate, glycogen and alkaline phosphatase and others. It also lowers triglyceride, cholesterol and LDL and considerably enhances superoxide dismutase and catalase action indicating the lowering of lipid peroxidation.

Hypourecimia effect – Uricemia induced by the high fructose diet is a metabolic syndrome causes an increased level of uric acid in the circulation. The reduction of uric acid is an innovative treatment to control the diabetes also. The aqueous extract of S grandiflora leaves can bring the levels of uric acid and Creatinine down to the normal.

Inhibitory actions toward enzymes – The fruit and flower extracts of S grandiflora can lower Advanced Glycation End (AGE) products as well as the early glycation of hemoglobin (HbA1c). The inhibition of enzymes like α – amylase and α- glucosidase by the extracts which is responsible for the carbohydrate metabolism could be responsible for that actions. The alcoholic extracts show significant reduction of α – amylase (52 %) and α- glucosidase (56 %) activities. Considerable reduction (~ 50 %) of glycation to form HbA1c is also noticed when using the alcoholic extract of flowers. Although the presence of Piperidine, Cinnamaldehyde and Linoleic acid are identified as being the liable factors but the recent isolation of two proteins SGF60 and SGF90 are also seen to be the additional cause behind these effects.

Anti-inflammatory effect – The large reserve of flavonoids along with several triterpenes are the source of strong anti-inflammatory actions. It has been known that procyanidins and flavonoids enable to trap chemically the generated reactive oxygen and inducible nitric oxide. Flavonoids can also inhibit the enzymes liable for producing those reactive free radical species. The enzymes are COX, LOX and iNOS. By inhibiting them they prevent to generate the inflammatory mediators.

Anti-cancer effect – The alcoholic or other solvent extracts of S grandiflora leaf exerts significant anti-proliferative and apoptotic effects on various human cancer cell lines like breast (MCF-7), Liver (Hep-G2 & Hep-2), lung (A549) and colon (HT-29 & HCT-116) including neuroblastoma (IMR-32). Activation of caspase, decrease in mitochondrial membrane potential, reduction in the activation of NF-κβ were observed in all cases indicating the presence of effective constituent(s) within the leaf. The methanolic extract is particularly more effective toward the lung cancer cells, A549.

Miscellaneous effects –

1. Cardiovascular effects – lowering of cholesterol, LDL, VLDL and triglycerides by the leaf extract.
2. Anti-microbial effect – Highly potent against Bacillus cereus, Micrococcus luteus, Staphylococcus epidermidis, Clostridium sporogens, Streptococcus faecalis, Streptococcus pyogens, Staphylococcus aureus, Bacillus subtilis, Agrobacterium tumifaciens, Klebsiella pneumoniae, Salmonella typhi, Pseudomonas aeruginosa, Serratia marcesens, Entobacteria aerogens, Proteus vulgaris and Escherichia coli). The petroleum ether and alcoholic extracts exhibited mild antifungal property against the tested fungal strains like Cryptococcus neoformans, Gibberella fugikoroi, Rhizophus oligosporus, Neurospora classa, Myrothecium verrucasia, Aspergillus Niger and Candida albicans.
3. Anti-arthritic action – The effect is due to its potent anti-inflammatory actions.
4. Leucorrhea – The flower extract is used in treating leucorrhea for women caused by the imbalance of estrogen.
5. Anti-asthmatic effect – The bark extract shows broncho-dilatory and antiasthmatic effects.
6. Effect on memory – The ethanolic extracts of S grandiflora seeds show significant neuroprotective role among the laboratory mice experiments. The extract reestablished memory in case of drug (Celecoxib) induced amnesia within the animals. Further it reduces the action of Acetylcholine esterase and restore the antioxidant enzymes like SOD, GSH and Catalase in the experimental animals. The extract helps improve cognitive dysfunction in drug treated animals while modifying the cholinergic system. In that way, it is a good preventive substance in developing Alzheimer’s disease by blocking any oxidative stress. Also inhibition of advanced glycated end product (AGE) formation is an additional aspect in this regard because presumably those are one of the constituents in Alzheimer plaques of brain.

 

Tricosanthes dioica / ‘Pointed gourd’ / পটোল / পলতা।

General feature: The plant belongs to the Cucurbitaceae family genetically analogous to squash or cucumber. In that way, it is vine by the nature except being perennial. The leaves are heart shaped and grown over the fence or any support. It is considered to be a native of the Indian subcontinent. It is dioecious having both male and female botanical organs within the same plant body. The fruits are dark green with frequent white stripes and the shapes vary from oblong to almost round having 3 to 6 inches in length and 1 – 2 inches in diameter. The flowers are tubular and white and take ~ 20 days to bloom.  The botanical name is Tricosanthes dioica (T dioica) whereas in English it is often termed as ‘Pointed gourd’. In India, its name changes by the regions. The plant has tuberous taproots. The cuttings are used for propagation because seeds germinate poorly. In Bengal it is commonly called Patol (পটোল), a fabulously popular vegetable that grows under hot, humid or moderately warm condition in well-drained sandy soil. This vegetable is produced in West Bengal, Assam, Orrissa, Bihar and Uttar Pradesh where it is often cooked to make curry by mixing with spices or occasionally using the fish. The plant parts are used either for cooking or as folk medicines.  In that regard, particularly the use of T dioica leaves are noteworthy which bears the name as Palta pata (পলতা পাতা) in Bengali. The fresh green leaves are used to make curry or fried by dipping into the lentil batter. A number of studies were conducted to evaluate its folk medicinal use. The plant shows no toxicity concerning its use as vegetable using leaves, roots, seeds or stems besides the fruits.

Ethno-medicinal uses: The fruits and leaves are frequently consumed as vegetable but cooked in different ways by following regional guidance. The leaves are considered as tonic although it acts as febrifuge and additionally preventing the liver or spleen enlargement. As described by the ancient Indian apothecary literature ‘Charaka Samhita’ leaves are the good antidote for alcoholism and jaundice. It can be used also to alleviate edema and alopecia. Further, it acts as antipyretic, diuretic, cardiotonic as well as laxative. Recent studies and identification of numerous phyto-chemicals confirms the medicinal behavior also finds something more. Following are the few folk uses: A) Leaves are used to hyperacidity; B) Anti-parasitic, B) Anti-periodic, C) Febrifuge, D) Anti-coagulants, E) Blood purifiers, F) Antiseptic, G) Tonic. The fruits improve appetite and digestion.

Several traditional uses of T dioica / Patol (পটোল)

Country	Region	Plant parts	Use
Bangladesh		Fruit	Treating teeth, fungal infection in nail, bad Smell in mouth
		Leaf	Acidity and constipation
India	West Bengal	Fruit	Treating chicken pox and its scar
		Leaf	Diarrhea
	Orissa	Fruit	Tonic, Febrifuge, Skin disease, Spermatorrhea, Laxative, Enlargement liver & spleen.
		Leaf	Alopecia, fever, hemorrhage, fistula, leprosy, Erysipelas, diseases of mouth, inflammation, Wounds and expectorant.
		Root	Febrifuge, Cathartic, Tonic, ascites, anasarca.

Phytochemicals and its physiologic role: Each part of the plant is a large source of numerous phytochemicals which are identified as, peptides like Trichosanthin, lectin, several triterpenes  eg, Curcurbitacin B, Euphol, α – Amyrin, β – Amyrin, Lupeol, Traxerol, Betulin, Karounidiol, Sterols, Steroidal saponins, Tannin and flavonoids.

Trichosanthin (TCS) is the most notable component among all of them. It is a type -1 ribosome inactivating protein (RIP), 24-kDa molecular weight containing ~ 247 amino acids. It inactivates the ribosome by site specific cleaving of N – C glycosidic linkage preventing elongation factor for binding to the 60S ribosomal unit exerting an arrest of protein synthesis. TCS prevents HIV by increasing CD4⁺ T cells in virus infected patients. It enables to prevent Hepatitis B and tumor growth while exerting apoptosis in numerous cancer cell lines by activating caspase – 3 and -8 pathways increasing intracellular ROS causing cell cycle arrest at the G1 phase. During that act intracellular Ca⁺² level goes up with simultaneous lowering of cAMP and PKC subsequently inhibiting the telomerase activity. It could be the reasons involved in the anticancer act. Further, the peptide inhibits tumor migration and angiogenesis in nude mice showing no side effects. Among the affected cancer cell lines are cervical, breast, prostate, lung, prostate, choriocarcinoma, melanoma, colon, hepatoma, stomach, lymphoma and several others. The peptide also acts as a potent abortifacient and immune suppressant.

Besides the TCS, large reserve of sterols, tetra cyclic and pentacyclic triterpenes have been identified and characterized in the roots, seeds and leaves of the plant. The root synthesizes noticeable amount of colocynthin, hentriacontane, cucurbita-5, 24 dienol (saponins) a bitter glycoside and tannins. The fruit contains high level of Ca⁺², Mg⁺² and Fe⁺², nicotinic acid (vitamin – B₃), riboflavin (vitamin – B₂), vitamin – C, thiamine (vitamin-B₁) and serotonin.

Cucurbitacin B is isolated from the T dioica fruit. It is a tetracyclic terpenoid. The compound has been widely studied for its potent anticancer role particularly when administered with low doses of methotrexate or curcumin against multi-drug resistance cancers like human hepatoma. Synergistic effects are observed in both the cases.

α- & β – Amyrin – The isomers are pentacyclic triterpenes. It is mostly found in the root. They show antimicrobial and antifungal property. Additionally, they also exert anti-nociceptive and anti-inflammatory actions by activating Cannabinoid receptors (CB₁ & CB₂) while preventing the generation of cytokines and the expression of NF- κβ, CREB and COX-2. Further the β – isomer inhibits the Lipoxygenase actions too.

Euphol – It is also a triterpenoid found in the root. It has several biological properties like hypotensive, anticolitis, anti-inflammatory, antinociceptive and antiviral effects. The anti-nociception effect is mediated by its interaction with the cannabinoid receptors, CB₁ and CB₂. The recent studies further indicate that Euphol has anti-cancer role especially toward breast and gastric cancers by arresting the cell cycle and ERK1/2 mediated apoptosis.

Taraxerol – It is an oleanane (oleanane is a triterpene structure which is the central core of many plant products particularly the triterpene) triterpene isolated from the root of T dioica. The compound possesses strong anti-tumor, anti-inflammatory, antimicrobial and anti-venom (snake) activities. It potently inhibits mammalian sarcoma 180 cell line and few mammary tumors implanted in nude mice. It is further effective against human gastric epithelial cell lines eg, AGS. It is also active against human glioblastoma, U87. The compound induces cell cycle arrest and promote apoptosis. In addition it also induces autophagy and inhibition of cell migration. Besides these, its further action is to inhibit cyclo-oxygenase and acetylcholine esterase and reversing the insulin resistance in adipocytes, 3T3L1.

Lupeol – It is also a triterpene found in many vegetables, fruits and medicinal herbs. It is effective against various ailments like inflammation, arthritis, diabetes, renal problems, cardiovascular problems, microbial infections and hepatic toxicity also against numerous cancers.

Karounidiol – It is a triterpene of multiflorane type isolated from the seeds. It is very active against tumor promotion when induced by phorbol ester also shoed cytotoxic potential against several tumors especially toward the renal cancer cell lines.

Betulin – It is also a triterpene identified and isolated from the seeds of T dioica. The compound is previously known for its antiseptic and anti-rachitic properties. Afterwards the investigation leads to the fact about its numerous biological effects eg, lowering of cholesterol, anti-inflammatory, hepato-protective, wound healing, anti-tumor and choleretic (stimulation of bile secretion) effects. Studies indicate that its cholesterol reducing property is due to inhibitory action on the maturity of sterol regulatory element-binding protein. Inhibition of this protein lowers the cholesterol synthesis. In that way, it reduces atherosclerosis. As per further action, it enhances insulin synthesis.

Important sterols – Appreciable number of sterols have been isolated particularly from the roots of T dioica. Among those 24 – methyl-cholesterol and 28 –isofucosterol appear to be the most important ones. They have antibacterial activity against many particularly effective for Bacillus spp. (spore forming bacteria) and Ochrobactrum pseudogrignonese.

Major phyto-compounds identified in T dioica.

Parts of plant	Compound	Nature
Root	Euphol	Triterpene
Root	Tirucallol	Triterpene
Root	Cycloartanol	Triterpene
Root	Taraxerol	Triterpene
Root	β- amyrin	Triterpene
Root	Butyerospermol	Triterpene
Root	Isomultiflorenol	Triterpene
Root	24 – methylene – 24 – dihydro- lanosterol	Triterpene
Root	α- amyrin	Triterpene
Root	Lupeol	Triterpene
Root	24 – methylene-24-dihydro- parkeol	Triterpene
Root	24 –methylene-cycloartanol	Triterpene
Root	Multiflorenol	Triterpene
Seed	7-oxo-dihydro-karounidiol- 3-benzoate	Triterpene
Seed	Karounidiol-3-benzoate	Triterpene
Seed	Karounidiol	Triterpene
Seed	7-oxo-dihydro-karounidiol	Triterpene
Seed	Betulin	Triterpene
Seed	29 – hydroxy-	Triterpene
Seed	Cucurabita-5,24-dienol	Triterpene
Root	24-methyl-cholesterol	Sterol
Root	24-methylene-cholesterol	Sterol
Root	24-methyl cholesta-7,22-dienol	Sterol
Root	24-ethyl cholesta-5,22-dienol	Sterol
Root	24-ethyl cholesta-5,22,25-trienol	Sterol
Root	24-ethylcholesta-8,22-dienol	Sterol
Root	24-methylenecholest-7-enol	Sterol
Root	24-ethyl-cholesterol	Sterol
Root	24-ethylcholesta-8,22,25-trienol	Sterol
Root	24-ethylcholesta-5,25-dienol	Sterol
Root	24-ethylcholesta-7,22-dienol	Sterol
Root	24-ethylcholesta-7,22,25-trienol	Sterol
Root	28-Isofucosterol	Sterol
Root	24-ethylcholest-7-enol	Sterol
Root	24-ethylcholesta-7,25-dienol	Sterol
Root	28-Isoavenasterol	Sterol
Root	Avenasterol	Sterol
Root	Colocynthin	Gylcoside
Root	Trichosanthin	Protein
Fruit	Cucurbitacin	Triterpene
Fruit	Vitamin A	Vitamins
Fruit	Vitamin C	Vitamins
Fruit	Nicotinic acid	Vitamins
Fruit	Riboflavin	Vitamins
Fruit	Thiamine	Vitamins
Fruit	Serotonin	Miscellaneous
Fruit	Carotene	Miscellaneous
Leaf	24-α-ethyl-20-ene-hydro-stimasterol -8β-:14β-di-3-O-β-D-xylo-furanoside	Saponin

Pharmacological actions: Numerous pharmacological effects concerning different parts of T dioica plant are already extensively studied both in vivo and in vitro. Number of cases of human studies are also officially reported. The major pharmacological actions which are studied are given below.

Anti-hyperglycemic effect – The effect has been tested in animal models using Streptozotocin induced diabetic rats. By administering the fruit extract, a significant lowering of blood glucose levels has been observed in fasting (~ 29 %) and postprandial conditions (~ 31%). Additionally, reduction in the level of AST (23 %), ALT (37 %) and ALP (35 %) and serum creatinine (36 %) are also noticed. Almost identical results are seen while using the seed extract. The leaves of T dioica produces near similar results but the effect is more pronounced in case of mild diabetic rats. In that case, the glucose level is dropped by 41% for fasting and 87 % for postprandial condition. Further, leaf and fruit extract cause considerable loss in the body weight.

Anti-hyperlipidemic effect – In animal experiments using the rabbits, the oral administration of aqueous fruit extract showed strong hypocholesteremia and hypotriglyceremic effect. The total cholesterol level is decreased by 57 % whereas the triglycerol is reduced by 19 % and the HDL is enhanced by 33 %.

Antitumor effect – The root extract at high doses showed significant anti-tumor activity which is possibly due to anti-oxidant behavior. The presence of Trichosanthin is presumably the underlying cause.

Anti-inflammatory action – The extract of T dioica stem and leaves by ethyl-acetate, methanol or chloroform showed potent anti-inflammatory role in animal experiments. The attenuation of TNF- α, COX-2 and NF- κβ are noticed in all cases which is reason behind that anti-inflammatory effect.

Anti-nociception effect – The effect is solely mediated by the triterpenoids present in the plant as evidenced by various animal experiments.

Miscellaneous actions –

A) Anti-oxidant; B) Cytotoxic; C) Hepato-protective, D) Chemo-preventive; E) Immunomodulatory; F) Wound healing; G) Anti-pyretic; H) Anti-fungal; I) Neuro-pharmacological actions; J) Anti-ulcerative.

Hibiscus / জবা ফুল।

General features: It is a flowering plant belonging to the Malvaceae family. The genus is very large containing several hundred species including both annual and perennial categories. The plant is grown in tropical or subtropical climate displaying flowers of spectacular colors. Due to the vibrant flower color, they are mainly cultivated for the ornamental / decorative reasons forgetting the scientific or medicinal role behind. The generic name was introduced from the Greek ‘Hibiscos’ as inscribed in the legendary book De Materia Medica (large five-volume encyclopedia relating to the herbal medicine and its medicinal role) by the famous Greek physician, scientist and pharmacologist, Pedanius Dioscorides in ~ 40 AD while working for the Greek Army. The book is still widely mentioned even long after his demise over 1500 years ago. Hibiscus / Jaba (জবা in Bengali) is a deciduous shrub producing dark green leaves that can reach ~ 30 feet height and 15 – 20 feet wide in a frost-free climate.  They can be grown short and single stemmed by virtue of pruning. The peripheral diameter of a flower is ~ 6 inches.  They are versatile in color ranging from white, beige, yellow, peach, purple and red or even mix. They are trumpet shaped (except Hibiscus sabdariffa) and very prominent, holding five or more petals. The dark green leaves are alternate, ovate or lanceolate showing toothed or lobed margin which are approximately 6 – 9 inches in length and 1- 1.5 inches wide which also depends on the nature and variety of species. The fruit is five lobed capsule holding numerous seeds within each lobe which gets released when the capsule splits open at maturity.

Cultural and religious features: The flower is the emblem of women’s emancipation. In Europe and America the flower symbolizes a perfect woman or wife. In Victorian England offering a Hibiscus bunch is the acknowledgement of woman’s delicate beauty. In China it implies fame and glory. Concerning the religious feature, red hibiscus has a special place in the Hinduism of India. In rich and colorful cultural heritage and mythology, hibiscus has a significant role. As per the Hindu mythology, every God / Goddess has the respective beloved flower which signifies individual’s nature and fondness. In that regard, hibiscus is convoyed with the Goddess Kali. She is a furious expression of primordial spirit and energy leading to death and destruction as well as the birth and creation. The legend indicates that being superbly empowered by the Gods at heaven, the Goddess went on a rampage to destroy the demonic empire terrorizing the world, which later turned unstoppable. Following deep consultation, the Gods at heaven sent the husband, Lord Shiva who lay down on her way. Inadvertently stepping on Him, she lost the fury out of deep embarrassment that eventually stopped her the destructive battling move. Being greatly embarrassed, the Goddess stuck out her tongue which is a common norm unconsciously practiced by the Indian women at their embarrassing moment. To the Hindus, the red hibiscus represents Goddess’s bright red tongue. But the very act universally represents the momentary act of sudden embarrassment for all women. To the contrary, the red hibiscus symbolizes Kali’s bloodlust fury which insentiently possessed over her at the battling moment. Anyway, according to the Hinduism, the flower is a mystic sign of female empowerment which raises a pulse in the force of human life.

Household use and health benefits: Hibiscus of all varieties are frequently employed for numerous food supplements claiming to provide several health benefits. The dried flowers are used as spices in Latino cooking. One of the prominent varieties that is largely used is Hibiscus sabdariffa / Roselle in making jam or jelly. In India, it is used for making Chutney (Indian sweet and tart dish). Additionally, those having the dark or light red colors are used either in the cooking or making popular drinks in many tropical regions. Among the drinks the most popular one is Hibiscus tea. Red colored flower, botanically named as Hibiscus Rosa – sinensis (লাল জবা) is commonly found and abundant in nature. It is used as spices in the Mexican cooking for coloring food or drink. Hindus in India use it for worshipping the Goddess, Kali. Besides flowers, the dried leaves and dark red calyces are also packaged for making tea which is slightly sour or tart by the taste. In ancient Egypt, hibiscus tea is consumed to lower the body temperature, chronic heart and nervous disorders. It is a potent diuretic and enhances the urine production. In recent days, the plant draws attention for several of its beneficial role on health like lowering of high blood pressure and cholesterol levels. It also has high potential for having anti-cancer regimen also aiding the weight loss and accumulation of undesirable body fat due to its role on metabolism. Further it reduces the fat build up within liver which seems to be due to large presence of anthocyanins. Approximately 10 gm of dried calyces provide ~250 mg of anthocyanin. Generally considered to be safe but occasionally it interferes with the acetaminophen (Tylenol / Paracetamol, anti-inflammatory drug), chloroquine (antimalarial drug) or diclofenac (anti-inflammatory drug) although the effect is seen minimal. Concerning additional effects, it lowers the bioavailability of several other drugs. Interestingly, the plant / flower extract successfully controls the head lice.

   Hibiscus sabdariffa / Roselle / অম্লমধু।

Hibiscus sabdariffa / Roselle: It is perhaps the most usable variety among entire family because of its fruity appearance and taste. In India, it bears numerous names in different regional languages eg, in Maharashtra it is called Ambadi whereas in Bengal it is named as Amlamadhu (অম্লমধু), meaning sweet and sour taste. It is incredibly popular in the Myanmar, thus often used in many Burmese cuisine which is cooked with green chilies, vegetables and dry fish. In Maharashtra, Gujrat and other parts of India, Ambadi is normally cooked with the vegetables and eaten with hand-made breads. In Andhra, it is cooked with the lentil and eaten with rice. In Philippine, a large section of foods are cooked with various Hibiscus flowers including Roselle. In Bengal, it is normally selected for making the Chutneys therefore consumed as a dessert. In other parts of the globe, like in several tropical islands in South Pacific and Caribbean, it is crushed and extracted for making syrup to use for the cold drinks while mixing with the other fruit juices. Hibiscus sabdariffa / Roselle is universally considered to be healthy due to the large reserve of Vitamin C and anthocyanins, strong antioxidants. Uniquely, the plant can exert strong anti-fertility effect. It stimulates the contraction of uterus as seen in the animal experiments although unfounded within human. But it acts as emmenagogue and stimulate menstruation helping abort the fetus in women. Concerning the pharmacological studies, it should not be consumed by the pregnant women.

Folk medicinal use: From veryancient times majority of the species belonging to this genus are used for various folk remedies. According to the Ayurveda, its tiny fruits are regarded to be tonic, aphrodisiac and astringent. In Unani medicine, the dried fruits are used for treating several urinary disorders. In many rural areas, the leaves are used for making poultice to cure boils, sores or sprains. The decoction made from flowers are employed to cure chronic bronchitis or other bronchial problems including the toothache. The bark mucilage is seen to act like an emmenagogue. The seeds of Hibiscus abelmoschus provide diuretic, demulcent and stomachic effects. It has also antiseptic, coolant, carminative, tonic and aphrodisiac property. The extracts of bark, flowers and fruits of all varieties are used to treat skin diseases like, eczema, scabies, psoriasis and ringworms. In Ayurveda, the Bhavapraksh (famous ancient medicinal science written in 14^th century by the great Hindu scholar, Bhavamisra who modernized the scientific aspects of herbal medicines considering its various drug actions) it has been mentioned that consuming hibiscus rosa-sinensis (লাল জবা) during menses would prevent pregnancy. The fact has been proven by numerous experiments on lab animals and human. The flower extract changes the estrous cycle imposing antifertility.

                                              Hibiscus abelmoschus / হলুদ জবা।

Medicinal actions of Hibiscus: The presence of large number of bioactive phyto-chemicals within all varieties of hibiscus identifies their natures are, flavonoids, anthocyanins, terpenoids, steroids, polysaccharides, alkaloids, amino acids, lipids, sesquiterpenes, quinones and compounds of naphthalene groups. Those are known to exert anti-bacterial, anti-inflammatory, anti-hypertensive, anti-fertility, hypoglycemic, anticancer, antifungal and antioxidative effects. Due to the extremely high level of phenolics and flavonoids, all members of this family draw interest both as a food supplement also having the subsequent medicinal role.

Anti-inflammatory – In laboratory experiment of both in vitro and in vivo using flower extract shows strong anti-inflammatory activity. The identified compound is Gossypin, a glycosyl- hydroxy flavone, which exerts potent anti-inflammatory property by inhibiting the NF-κβ activation pathway at ~ 10 µM doses preventing inflammation. The compound is synthesized at very high level in Hibiscus vitifolius but exists to a lesser extent within others.

                                                             Hibiscus vitifolius

Antimicrobial action – The powerful anti-microbial effect of fatty acid fraction from the stem bark is partly due to Canthin-6-one, a β-carboline alkaloid, synthesized within most members of the Hibiscus family but seen at a very high level particularly in Hibiscus syriacus. The compound is extremely cytotoxic exhibiting potent antifungal, anti-parasite and antimicrobial effect destroying both gram positive and gram-negative bacteria. Further, the aqueous or alcoholic extract of calyx from Hibiscus sabdariffa shows powerful antimicrobial property preventing number of pathogenic bacteria particularly methicillin resistant Staphylococcus aureus (MRSA) and several others. The presence of high level of protocatechuic acid and several of its glycosylated derivatives are noticed to be liable for the effect. The compound enables to induce apoptosis in human leukemia cell lines indicating anticancer effect. The other components like compound (3) Hibiscanal and (4) Hibiscanone can also prevent various pathogen.         

                         Hibiscus syriacus / Rose of sharon / Korean rose

Effect on fertility- Amongthe varieties, Hibiscus rosa-sinensis / লাল জবা has the most potent infertility effect particularly offered by the ingredients extracted by using either benzene or ethanol as a solvent. The infertility effect is mediated via the inhibition of implantation. Interestingly, the level of contents within the flower follows seasonal variation. Those collected during winter months show the highest potency afterward its effectivity goes downward following spring, rainy season and summer months. Several antifertility compounds are identified and characterized from various extracts. Among them two are seen to be the most potent / effective to prevent the pregnancy for both human and animals also nontoxic. In males, the extracts affect spermatogenesis as well as other functions of the testis and accessory the sex organs including pituitary.

Contrarily, the aqueous extract of Hibiscus macaranthus causes anabolic and virilizing effect which is indicated by the increment of serum testosterone level also enhancing spermatozoa count within the lumen of seminiferous tubules. Testis also show increased production of testosterone as well as the higher level of prostatic acid and phosphatase within prostate and testis. In case of Hibiscus sabdariffa the effect is quite opposite although for a long time it is considered to be an aphrodisiac. Its extract significantly lowers the epididymal sperm counts causing also the disruption of normal epithelial organization as well as hyperplasia of testis thickening the basement membrane. At higher doses, it disintegrates the sperm cells.

                                                          Hibiscus macaranthus

         
Two most potent anti-fertility compounds isolated out of ten active                                  components from Hibiscus rosa-sinensis

 

Antitumor effect- Theaqueous extracthibiscus sabdariffa flower and buds possess substantial antitumor property. In addition to the protocatechuic acid, the two other powerful cytotoxic compounds, Myriceric and Uncarinic acids have been identified. They show anti-proliferative effect by inducing apoptosis which is associated with the reduction of phosphorylation in retinoblastoma (RB) and subsequent Bcl-2 expression. The antitumor effect is observed also in human lung carcinoma, breast carcinomas, and leukemia and colon cancer cells. The studies reveal that apoptosis occurs via ROS mediated mitochondrial pathway.

Anti-tumor compound

Anti-hypertensive effect – Overa long time, the Hibiscus family members is widely famed for its powerful hypotensive or blood pressure lowering effect. In that regard, Hibiscus rosa-sinensis and Hibiscus sabdariffa are noticed to be very potent. Hibiscus rosa-sinensis, the red colored flower (লাল জবা) has several components that exert significant hypotensive effect. Experiments had proven that aqueous-alcoholic extract inhibits Angiotensin-I converting enzyme (ACE) which is the major underlying cause behind the hypotensive action. Several compounds (1& 8 – 13) presented in the list are identified to be also the major cause behind that inhibitory role. Those flavones can inhibit the actions of several serine proteases like elastase, trypsin and α – chymotrypsin which are often acting behind the hypertensive effects. The aqueous extract of Hibiscus sabdariffa produces strong vaso-relaxation when tested in vitro on the isolated rat aorta. The vaso-relaxation effect is mediated due to the inhibition of Ca⁺² influx from the surrounding medium inside the cell also simultaneous blocking the Ca⁺² release from the intracellular store of endoplasmic reticulum. Further, the extract acts as a potent diuretic by inhibiting Na⁺ and water reabsorption. It acts better than the loop diuretic, Furosemide since it does not cause over-reactivation of renin-angiotensin-aldosterone system maintaining K⁺ concentration in the body. In human studies, it has been noticed that Hibiscus sabdariffa extract can lower both systolic and diastolic pressure within the patients ranging from 30 to 80 years of age. The effect is somewhat better than the Captopril.

Hypo-cholesterolemic – The experiments on human and animals have convincingly proven that aqueous or alcoholic extract or even dried calyx of Hibiscus sabdariffa can lower the level of triglyceride, cholesterol and LDL and lipoprotein cholesterol or VLDL in a very dose-dependent manner by ~ 25 to 33%. Histopathologic examination also reveals the prevention of foam cell formation, inhibition of smooth cell migration and calcification of blood vessels. The reducing effect is supposedly mediated due to the racemization pathway of (+) hydroxy-citric acid / (+) HCA to (-) HCA with the help of enzymes from gut flora. The significant reduction is achieved when 10 % extract of Hibiscus sabdariffa was consumed. Biochemical studies already have proven that hypo-triglyceridemic effect is achieved by (-) HCA isomer via competitive inhibition of cytoplasmic enzyme, citrate lyase.

Hypoglycemic action – The compound 32 in below list isolated from the flower showed considerable hypoglycemic effect which is more than Glibenclamide or tolbutamide (sulfonyl urea drug) in both human and animals. The extraction from Hibiscus rosa-sinensis and Hibiscus sabdariffa indicates the most effect. They follow the mechanism of sulfonyl urea but not the biguanides (Metformin).

Antioxidant – The extract of Hibiscus rosa-sinensis and Hibiscus sabdariffa shows compelling antioxidant property compared to the others in its family. The extracts or else dried powders are known to exert strong anti-inflammatory actions which could be due to this antioxidant effect. It is noticed that the protocatechuic acid has strong impact in that regard since it prevents Nitric oxide synthase enabling to prevent inflammation or liver damage by the endotoxins. In addition, the large reserve of anthocyanins / flavonoids efficiently scavenges any endogenously generated free radicals within the body thereby protecting from inflammation, infiltration and necrosis. The aqueous extract or even dried powdered calyx of Hibiscus sabdariffa or Hibiscus rosa-sinensis are seen to prevent Cu⁺² induced oxidation of LDL in vitro signifying the powerful anti-oxidant role. The major antioxidant property is seen in Syriacusins A, B & C (18 – 20) although there are also others exhibiting potent similar role (compounds 21-31).

 

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List of several bioactive phytochemicals from different members of Hibiscus family

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Name of the plants	Bioactive components / Fractions	Functions / Activities
Hibiscus ablemoschus	Aqueous extract	Larvicidal effect
Hibiscus cannabinus	Tri-norcandalene phytolexins, Volatile oil of leaves.	Anti-fungal
Hibiscus elatus	Flavonoids	Anti-oxidant
Hibiscus macaranthus	Ethanol extract-aerial parts & roots Aqueous extract of leaves	Antifungal & antimicrobial Antifertility, Virilizing & Anabolizing effect
Hibiscus rosa-sinensis	Benzene & EtOH extract – flowers Aqueous extract – leaves Benzene, CHCl3 & EtOH extract of Flowers Glycoside of leaves EtOH extract of flowers	Antifertility Antifertility Antispermatogenic   Hypotensive, Antispasmodic Hypoglycemic Anti-convulsant.
Hibiscus sabdariffa	Oil fraction Protocatechuic acid and aqueous Fraction of flowers Polysaccharides, phenolic acids (of flower buds) & Anthocyanins Aqueous extract of flower EtOH fraction of flowers – Phenolics	Antifungal & Antibacterial Antibacterial Antitumor Antitumor Anti-hypertensive Antioxidant, smooth muscle Relaxant, anti-spasmodic.
Hibiscus syriacus	Seed oil Fatty acid fraction from bark Napthalenes from root bark Pentacyclic tri-terpenes Lignans from root bark	Antimicrobial Antifungal Antitumor, antioxidant Antioxidant Antioxidant

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Mollugo pentaphylla Linn / Pig weed / Carpet weed / গিমে শাক।

Mollugo pentaphylla Linn / Pig weed / Carpet weed / গিমে শাক।

General features: It is a perennial herbaceous plant which usually grows in open grassland. In many parts of the world, it is considered as a weed therefore bears an English name, Pig weeds. In Bengali, it is named as গিমে শাক, which is actually the native of tropical regions even it grows in almost every state of the USA and Canada. In ancient Ayurveda (Ancient Hindu apothecary) it is described as ‘Tropical beauty’ (গ্রীষ্ম সুন্দরক). It belongs to Mollunginaceae family of the flowering plants. It is less than a foot tall. The branches are slender, glabrous or hairless. The leaves are 0.6 – 1.2 inches in length and 0.06 – 0.12 inch wide, whorled, opposite and lance like. The flowers are grown in compound cymes or inflorescence and short stalks. They are white, green or orange colored.  The sepals are very small ~ 0.06 inch in length. The capsule is as along as sepals and spherical in shape holding large number of seeds, dark in color. More than a dozen of species of same genus exist in the nature. One of them is commonly known as Mollugo Hirta and Mollugo verticillata. They are identical in appearance and can be used for edible purposes. It is produced around September to October which is propagated by seeds dispersed via water in anthropogenic habitats. It tends to grow in sunny, sandy or stony sites in fields, teak forests, and low land and rice fields or in moist tropical condition. The growth is difficult to control only by the tillage since it can even flourish from the cut-stems. Although used as vegetable but it possesses a great deal of medicinal properties that are beneficial for the human health. The plant contains carotene, Vitamin C, saponins and many other chemical components including high level of Potassium nitrate. From the very ancient times it is used in rural areas as medicine and vegetable.

Use of folk medicine and edible vegetable: Whether an entire plant or extracts of the leaves is employed as important folk medicine in many South East Asian nations as anticancer, antitoxic and diuretic agents. It is adopted also for curing the mouth infections. The paste made out of leaves are applied frequently in rural India and Malaysia as a poultice to cure the leg sores. In India, it finds its uses as laxative, emengogue, stomachic and antiseptic medicine. In China, it is used to make soups to promote appetite whereas the extract prepared from the fresh roots is administered to cure eye diseases. In Thailand, the entire herb is utilized for anti-pyretic purposes. The burning of dried plant is traditionally used in Solomon Islands to repel the mosquitoes. In many places of India like in West Bengal and Bangladesh, it is consumed as a fried vegetable after frying with ghee (butter fat) which produces slight bitter taste. The infusion prepared from whole plant promotes menstrual discharge in women. The leaves smeared with warm oil is applied behind the ears to offer relief from the earache. Additionally, it has been recorded from the folk use that Mollugo pentaphylla provides several beneficial actions regarding health, providing anti-microbial, anti-cancer, anti-bacterial, anti-fungal, spermicidal, resisting / preventing / curing whooping cough and hepatitis. Recent animal experiments in the laboratory verified most of those acts including its anti-ulcer effect.

Phytochemical constituents and associated pharmacological role: The plant is a rich source of physiologically beneficial chemicals. Several ways of solvent extraction identifies common categories of chemicals, phytosterols, terpenes, flavonoids, saponins and organic acids synthesized within it.

Major ingredients of Mollugo pentaphylla Linn

Among the alcohol extracted components the major ones are cis – Vaccenic acid, Palmitic acid, Phytol, Octadecanoic acid, Stigmasterol, Benzoic acid, Vitamin E, esters of palmitic acid. Additionally, important isomers of tri-terpene naming Mollugogenol A, B and D are isolated which express anti-fungal action as well as spermicidal activity by inflicting damage to the sperm membrane due to increasing lipid peroxidation. Besides those components the herb contains varieties of flavonoids, terpenes and saponins.

Cis – Vaccenic acid lowers total cholesterol, LDL-cholesterol. Its level is seen high within orbitofrontal cortex for bipolar and Schizophrenics. Its oxidation produces body smell of old males.

Phytol is the precursor for synthesizing Vitamin E and K₁. It is a chemical deterrent to many predators.

Stigmasterol is a phyto-sterol which can prevent several cancers like Ovarian, Prostate, Breast and Colon. It lowers the serum cholesterol (~ 30 %) by inhibiting the intestinal absorption. The compound also antioxidant, hypoglycemic role also inhibits the thyroid.

Vitamin E – It is a fat soluble vitamin displaying strong anti-oxidant effect. It also helps in gene expression and intracellular signal transduction. It also helps lowering of cardiovascular, cancer and dementia problems. It reduces scar tissues resulting in wound healing.

Apigenin – The flavonoid has multiple pharmacological role: A) Chemo-preventive due to autophagy action; B) Inhibits drug metabolism by inhibiting mitochondrial enzyme CYP2C9: C) Prevents renal damage; D) Modulates GABA_A receptor; E) Antagonist to the NMDA receptor; F) Non-selective antagonist toward µ-, δ- and κ- opiate receptors; G) Inhibits COX-2 causing anti-inflammatory effect.

β – Sitosterol – This phyto-sterol is a precursor to many anabolic steroids. It reduces circulating blood cholesterol and reduces the possibility of benign prostate hyperplasia (BPH).

Mollugogenol A, B & D – These triterpenes isomers have potent anti-fungal, anticancer and anti-microbial effects in human and cattle cancer cells.

Medicinal and pharmacological effects: The underlying mechanisms behind many of the medicinal effects have been already identified as well as the component(s) involved but a section still remains unknown. Below is the few known actions exerted by this vegetable herb.

Antiulcer effect – The alcoholic extract shows potent anti-ulcer effect in pyloric ligation induced ulcer or ethanol induced ulceration of laboratory rats. It was effective against stress induced ulceration also. The effect is very comparable to Ranitidine. Analysis of phyto-constituents show the presence of flavonoids, saponins and glycosides.

Hepato-protective effect – The similar extract exerts significant protective effect on liver function when orally administered with or without CCl₄ in usual induced animal model using CCl₄. The liver function has been determined by measuring the indicators like, serum Glutamate oxaloacetate transaminase (SGOT), serum Glutamate pyruvate transaminase (SGPT), Alkaline phosphatase (ALP), Acyl carrier protein (ACP) and Bilirubin. The protective effect is identified due to flavonoids, tannins and saponins.

Anthelmintic effect – The ethanolic fraction has significant anthelmintic property when tested on Ascardia galli (parasitic round worm) and Pheretima posthuma (Earth worm). The effect is comparable to the either control Piperazine citrate or Albendazole. Possibly, more than one components are active since the above known drugs work via different mechanisms. Piperazine works by paralyzing via the GABA_A receptor which is conspicuously expressed in the parasite thereby allowing pass through the intestine. On the other hand Albendazole works by killing them while disrupting the micro-tubule assembly.

Anti-inflammatory, anti-pyretic and analgesic effect – The anti-inflammatory of ethanolic extract of M pentaphylla has been verified in the laboratory by various ways within experimental animals using Dexamethasone as a control. The same extract reduces fever within 3.0 hrs within the animals having Brewer’s yeast induced pyrexia. In standard tail immersion experiments using painful acetic acid induced writing model, the extract significantly lowers the effect of painful stimulus. The presence of several saponins, phyto-sterols and anti-oxidants are identified to be the underlying causes.

Anticancer effect – Both in vitro and in vivo studies on varieties of human cancer cell lines even sarcomas, the alcoholic extract shows extreme cytotoxicity which is somewhat absent for normal cells / tissues. The major identifiable components are Apigenin, Mollupentin, Mollugogenol A, B & D, β – sitosterol and Oleanolic acid. Each individual component follows different pathways to exert anti-neoplastic actions.

Major anticancer compounds in Mollugo pentaphylla

Anti-diabetic effect – The aqueous extract of fresh leaves shows potent anti-diabetic effect when tested on normoglycemic and alloxan induced hyperglycemic rats for 30 days period (250 – 450 mg / kg). The anti-diabetic action has been evidenced by the considerable fall in blood glucose besides the ability of enhancing the plasma insulin level. Further, there is also the lowering of oxidants and simultaneous increase of antioxidant enzymes in the liver. The presence of β – Amyrin type tri-terpene has been identified as being the active ingredient along with the conjoint effects of other anti-oxidants.

Anti-oxidant action – The aqueous leaf extract show strong anti-oxidant and free radical scavenging activity which is almost similar to the ascorbic acid. The presence of numerous anti-oxidant compounds is the underlying cause.

Miscellaneous effects – A) Anti-bacterial and anti-microbial; B) Laxative; C) Anti-parasite; D) Spermicidal; E) Photo-protective; F) Anti-microbial.

Chenopodium album / Fat Hen /Bathua / বেতো শাক।

General features: The botanical name is Chenopodium album Linn but commonly called Fat hen / Goose foot or Pigweed. Some also call it Wild Spinach. It is green herbaceous edible plant which wears occasionally a touch of reddishness. The entire plant is edible. In India, it is named as ‘Bathua’ in Hindi and ‘বেতো শাক’ (Betho –shak) in Bengali. The plant belongs to Amaranthaceae family of Chenopodiaceae genus. It grows annually to reach 3 – 5 ft height, spreading ~ 3 ft around. The erectile stems are succulent. Both stems and leaves are inodorous and is used as vegetable. The leaves are somewhat oblong or lanceolate, irregularly lobulated in shape having saw like edge. They are 2 – 5 inches long 1.5 – 3.0 inches wide. Under the surface of leaf there exists removable white mealy layer. The leaves grow alternately as one at each node while rising up with the stem. The flowers are either bisexual or female and Cultivation and uses: The plant is cultivated mostly for vegetable need but the seeds are also consumed as grains for human and animal feed in many African and Asian nations. In many of the western countries as in Europe and America it is considered being weeds since it competes with the corn, soybean and sugar beet crops resulting in crop-losses still C album is ecologically beneficial. It attracts Leaf miners and other beetles. In that way it protects the neighboring crops. A green vegetable dye is also occasionally extracted from the young shoots to color wool or silk. The crushed fresh roots are used as a soap substitute in many rural areas.dense white spikes growing as branched inflorescence, 5 – 15 inches long, blooming at the tip or end of the branches. Flowering occurs within July to October. The fruits are tiny round pods that open around the tips displaying shiny small black seeds sticking inside in large number.  The plant amply occurs during winter season and used only for the culinary reasons. The chopped fresh leaves are often used for making the curries, soups, stuffed Indian bread (Paratha). The seeds are also included in the cooking and baking of breads or making beverages in the Northern Indian provinces like Himachal Pradesh and Kashmir. The genus of Chenopodium has several taxonomies. Although all are edible but some can provoke slight health problems. In that concern, C album is least to interfere any. Its native origin remains unknown. Carl Linnaeus, the famed Swedish botanist described it in his book ‘Systema Naturae’ in 1753 claiming to be a European plant. Although it is naturalized in Asia, Africa, North America, Oceania and Australia even available in the Antarctica, seemingly providing a notion that it grows anywhere particularly in the nitrogen rich soil.

Edible uses: It could be used as spinach substitute although it has bland taste, so often cooked with stronger flavored spices. Due to its carminative role it is frequently cooked with the beans to prevent gas or bloating. The sprouted seeds are also eaten with the salads. Occasionally, the dried seeds are grinded and mixed with flour to make chapattis. Before any uses, seeds are soaked in the water for overnight to remove saponins. Seeds have ~ 49 % carbohydrate, 16 % protein, 7 % ash whereas the leaves have ~ 4 % protein, 0.8 % fat, 9 % carbohydrate and 3 % ash. The fresh young flowers are used as broccoli substitute.

Nutritional values: The plant is majorly grown in the Northern Indian region and therefore its grains earn the name ‘Himalayan grain’ which is quite the same as Andean ‘Quinoa’ considering the average contents and nutrients. Ironically, some considers it only suitable for the poultry. But the Chenopod grain is better than wheat, barley, maize and rice. Its protein quality equals to the milk, enriched with high Lysine (~ 6g / 100g protein), Methionine (~ 2.5 g / 100 g protein) and Cysteine (~ 1.5 g / 100g protein). Although readily available in most parts of India still due to the lack of awareness its popularity is steadily decreasing, ignoring the fact even about its unique medicinal effects. It is remarkably inexpensive, also can be cooked as green leafy vegetable along with properly chosen regional spices. The leaves have high level of oxalic acid (lesser than tomatoes) therefore it is advised to consume less for the rheumatic and kidney stone sufferers. But repeated washing of chopped vegetable with cold water would remove the oxalic acid to a large extent. The cultivation of this crop would provide enormous nutritional support to the entire population. 

Medicinal uses: Although not considered as medicinal herb, but the plant has few subtle medicinal role besides the virtues of nutritious and healthy diet. The leaves possess anthelmintic, anti-inflammatory, anti-rheumatic, odontalogic and mild laxative properties. Its decoction is used in curing the tooth carry. The poultice prepared from leaves is applied to the swollen feet, rheumatic joint, bug bites and sunstroke to relieve pain and subsequent problems. The seeds can treat urinary problems especially, to prevent any semen discharge through the urine. The root extract is used to treat blood dysentery. Further the consumption of powdered herb suppresses the estrous cycle.  

Chemical constituents and pharmacological actions: The plant possesses essential oil, carotene and vitamin C. The leaves are enriched with essential oil and minerals especially regarding the potassium content. In addition to those seen below, it also contains tartaric acid, butyric acid, tri-ethyl amine and urease. The total protein content is ~ 203 g / Kg along with it the seeds contain high level of amino acids. Further, the Na / K ratio in this vegetable is less than 1.0 which is the reason behind its recommendation to include in diet for lowering the hypertension.

The presence of α – Pinene offers number of medicinal role. The compound is categorized as a bicyclic monoterpene and exists as four isomers thus available in the racemic form. It acts as a good bronchodilator also as an anti-inflammatory component. It inhibits acetyl-choline esterase thereby helping boosting the memory function. It is also a positive modulator of GABA-A receptor working via the benzodiazepine binding site imparting anxiolytic effect favoring the anti-panic action.

Ascaridole is naturally occurring organic peroxide. It is a powerful anthelmintic enabling to expel parasitic worms from the body. It is a major remedy for human to get rid of intestinal worms. It is also effective against the malaria. At high doses it produces toxicity causing several health problems including nervousness and depression.

p – Cymene is a hydrocarbon often counted to be a member of the terpene family. It has vaso-relaxant effect working via the K⁺ channel. Additionally, it exerts anti-nociception and anti-microbial properties. The production of NO and its subsequent role may be the underlying cause for its anti-nociception role.

d- Camphor is a terpene and exists in two enantiomers as (R-) and (S-). In nature it is available under racemic condition. It is used in the perfumery, culinary and medicinal purposes. The compound stimulates nerve endings creating hot and cold sensation. The hot sensation is exerted via TRPV3 and TRPV1 ion channels whereas the cold sensitivity comes from the stimulation of TRPM8 channel. The compound can induce tachycardia, vaso-dilation on skin also enhances secretion through the perspiration and urination. It can regulate dysentery / diarrhea. If used as emollient, it suppresses chest congestion created by the cough and cold.

Ferulic acid is a natural phenol which acts as a powerful antioxidant scavenging / preventing the generation of free radicals like reactive oxygen species (ROS) which causes DNA damage and accelerates the process of aging. On the other hand it inhibits melanin production on skin inducing the process of whitening.

Geraniol is a monoterpene. It has many biological properties while behaving like, insecticidal, mosquito repellent, anti-microbial, anti-oxidant, anti-inflammatory, anti-cancer and anti-epileptic. It also helps vascular permeation of the skin.

 Pinocarvone is a bridged hydrocarbon like camphor. It possesses few biological properties eg, anti-bacterial, acaricidal (kills ticks and mites), anti-nociceptive and anti-gastric ulcer.

Limonene is a monoterpene hydrocarbon mostly used as food flavoring agent and majorly resides in the citrus food. It is effective in relieving gallstone, gastroesophageal reflux disease or heartburn.

α – Spinasterol has several important pharmacological role. It inhibits Glomerular mesangial cell proliferation (IC₅₀ ~ 3.9 x 10^-12 g / ml) caused usually due to the high blood glucose. It shows therapeutic potential to control the development of diabetic neuropathy. It can prevent prostatic hyperplasia induced among the animals in laboratory experiments. So it is counted as being beneficial for managing benign prostate hyperplasia. It is a novel antagonist for TRPV1 receptor imposing anti-nociceptive action. In addition it also displays anti-inflammatory effect.

Long list of other components within C album possess enormous biological and physiological effects which are beneficial to the human health as depicted below.

Important pharmacological effects:

1. Antioxidant effect – C album possesses large number of anti-oxidant phyto-constituents such as flavonoids, glycosides of Kaempferol, quercetin, Isorhamnetin, catechin and anthocyanidins.  Approximately eight flavonoids along with their glycosides have been isolated. All of them are potent in inhibiting the free radicals and oxidative chain reactions within tissues and membrane. They are reducing agents thus enable to donate hydrogen thus subsequently quenching the singlet oxygen.
2. Anti-microbial actions – The major effects are noticed regarding anti-microbial and anthelmintic actions. The actions are duly imposed by the alcoholic or solvent extracted components of which many are not fully identified yet. The solvent extract is active against Staphylococcus aureus, Bacillus subtilis, Bacillus polymexia, Sreptococcus faecalis, Pseudomonas aureogenosa, Salmonella typhi, Vibrio cholera, Shigella dysenteria, Escheria coli, Penicillium notatum, Aspergillus niger and candida albicans. The components in extract prevents the progression of those diseases. Further it has the ability to inhibit the cell growth of human breast cancer cell lines by enhancing the cellular toxicity. The aqueous extract of C album has preventing action on Staphylococcus aureus. It displays strongest antifungal activity causing 96 % reduction of fungal growth.
3. Anti-pruritic and anti-nociceptive activity – The typical model of scratching behavior induced by Serotonin can be inhibited by the ethanolic extract of C album. It is previously recorded that serotonin facilitates the process of inflammation and pain also potentiates the effects of other pain mediators like noradrenaline or Prostaglandin E. It is thus hypothesized that the anti-nociceptive effect of extract could be due to the inhibition of serotonin’s action. Numerous reports confirm that alcoholic extract of C album is safe causing no adverse physiologic effect while curing inflammation and relieving pain.
4. Anthelmintic effects – Parasitic / worm infection is recorded among 2 billion people of the poor and developing nations particularly within the tropical and subtropical regions of the world. Schistosomiasis accounts for ~ 40 % of all tropical diseases. The subsequent effects of Schistosomiasis infection are malnutrition, anemia, cognitive impairment, stunted growth which perhaps leads to the other diseases. The leaf extract has potent anthelmintic, antiphlogistic, anti-rheumatic properties.

Ipomoea Aquatica / Water Spinach / কলমী শাক

Ipomoea Aquatica / Water Spinach / কলমী শাক

General features: It is semi–aquatic tropical plant belonging to the convoluvalaceae family, normally considered as greens but also as a vegetable for its tender shoots and leaves. About 600 – 700 species of Ipomoea are found allover the tropical and subtropical regions. Being in the same family, Ipomoea aquatica tends to grow under the similar tropical conditions especially in the South East Asian regions like in West Bengal, Bangladesh, Thailand, Vietnam, Indonesia, Malay, Burma, Philippines, Cambodia and Srilanka where it is used in almost daily cuisines although many members of its family are also not edible which are thereby used for decorative reasons. Despite culinary uses, the plant is recognized for its medicinal values, thus often used as folk medicine in the rural areas. In Bengali it is widely known as Kalmi Shak (কলমী শাক). Its origin remains unknown. In english it is often called Water or Chinese spinach. I aquatica grows in the heavily moist watery soils under bright sun light. The stems are 7 – 10 ft high and hollow which makes to float on water. The leaves are arrow headed shape or could be lanceolate, 2 – 6 inches in length and 1 – 3 inches broad. The flowers are white and trumpet shape with lilac coloration inside the center. It spreads via planting of cuttings of the stems or spreading of the seeds produced from flowers creating seed pods. It grows naturally in the waterways requiring little or no care. It is a multicellular photosynthetic eukaryotes belonging to the Plantae kingdom. It is a part of many South Asian diet in the rural areas. In the list of USDA it is considered to be invasive weed particularly in the states of California, Florida and Hawaii. In Texas it is allowed for cultivation and commercial sale as an exotic vegetable. It invades wetlands blocking the passage of boats by  creating dense floating mats. But the plant is heavily used for edible needs for its large popularity among the South East Asian populations. It is usually cooked with shrimp, cuttlefish along with the chili pepper, garlic, ginger and soy sauce. The chopped fresh plant is blanched with different vegetables using peanut sauce to make salads according to the Indonesian cuisine. In Thailand, it is normally cooked with green papaya to make cuurry. In Philippine it is cooked with meat or fish adding soy sauce along with boullion cube (dehydrated blocks of meat, vegetables and other stocks). In Japan it is cooked like Tempora, frying after dipping into the batter. In West Bengal and neighboring Bangladesh, it is proverbial not to consume this plant during rainy season but no exact reason behind this mythical practice is very unknown. Thus it remains as a mystery.

Ethnomedicinal use: The plant finds its ethnomedicinal uses regarding numerous illnesses which has been seen practiced from the ancient times. In ancient Ayurveda, the use of I aquatica has been mentioned to cure jaundice and nervous impairment via the oral administration. Since then, it is also frequently used to cure liver diseases, diabetes, constipations, abcesses, mental and intestinal problems. The similar uses are noticed in many African nations like Somalia and Tanzania. It is also effective against hypertension, CNS problems and mental depression. It acts as good antimicrobial agent against E Coli, Bacillus subtilis and Pseuodomona aeruginosa. In rural areas, it is used as anti-inflammatory, anti-epileptic and hypolipidemic agent. For a long time it is believed to offer nootropic effect which has been established by examining the rat hippocampus. The plant inhibits Prostaglandin synthesis which is possibly a part of the reason behind its anti-inflammatory role. The plant extract is effective against leucoderma, leprosy and ringworm. It is also a good emetic agent. Many of its ethnopharmacological properties are still not identified. Some members of the Ipomoea genus contain ergot alkaloids which may exert hallucinations. But I aquatica does not induce any hallucination.

Important phyto-chemicals and its medcinal actions: The plant,I aquatica contains numerous phytochemicals like flavonoids, vitamins – A, B1, B2, B6, B12, C, E and U [S-methyl-methionine used for treating gastric and intestinal ulcers], amino acids, alkaloids, steroids, lipids, phenolics, saponins, tannins, β – carotenes, reducing sugars. It also contains aliphatic pyrrolidone amides, carotenoids, hentriacontane, β – sitosterol and its glycosidesides, Prostaglandins, Leukotriene, N – trans – and N-cis – feruloyltyramines. In addition to have various amino acids and sugars it synthesizes several organic acids also like, malic, citric and oxalic also several long chain fatty acids eg, behenic, melissic and others of same kind. The plant has high level of Potassium (312 mg / 100 g) along with the others it possesses moderate level of Na, Ca and Fe. Plenty of polyphenols like myrcetin, quercitin, apigenin and kaempferol are detected. Approximately, tweleve pigments / flavonoids have been detected eg, lutein, anthraxanthin, flavoxaxanathin, auroxanthin, luteoxanthin, neoxanthin, β – carotene, violoxanthin, cryptoxanthin, neoxanthin A & B and several others.

The major bioactive phytocomponents identified are:

1. Nortropane alakloids: Calystegines B1, B2, B3 & C1. Calystegines B1, B2 and C1 have potent inhibitory activity toward lysosomal β – glucosidase and the isomer B3  moderately inhibits α – and β – mannosidase. It is usually good inhibitor of many microbial growth via the inactivation of those enzymes which help progression of infection. It can inhibit Prostaglandin synthesis thus expressing its anti-inflammatory role. Although some of the members of nortropane family exerts hallucinating effects but these ones do not.

2) Phenolics: N – cis – feruloyl tyramine, N- trans-feruloyl tyramine and 3,5-di-O-caffeoyl-quinic acid. The former two members act as the inhibitor of Prostaglandin synthesis whereas the later one possesses hypoglycemic, antioxidant, antimutagenic, anti-neoplastic behavior. It can inhibit the HIV replication. As a further measure, it expresses antifungal, antispasmodic and collagenase inhibitory property. Similar actions are noticed in other isomers of 3,4-di-O-caffeoyl-quinic acid (isochlorogenic acid).

3) Flavonoids: 3α, 7β-O-d-diglycopyranosyl-dihydroquercitin, it shows potent anti-oxidant, anti-microbial and cytotoxic effects.

Pharmacological actions: Theknowledge offered by ancient Ayurveda compels for the folk application which has been proven medicinally effective in curing or preventing number of ailments. The underlying pharmacological reasons have been identified by various laboratory experiments. Some of them are described below:

1. Anti-oxidant effect – Anti-oxidant and radical free radical scavanging activities of aqueous and alcoholic are very dominant. Among the identifiable components 3α, 7β-O-D- di-glycopyranosyl-dihydro-quercitin extracted from the leaves possesses the highest level.
2. Ant-inflammatory effect – The methanolic extract showed strong anti-inflammatory and analgesic effects when tested in the laboratory rats. N-cis-feruloyl tyramine and its trans – isomer  found majorly inside the root inhibits prostaglandin synthesis.
3. Anti-diabetic effect – The aqueous extract possesses hypoglycemic and anti-diabetic effects. The identifiable reason is by preventing glucose absorption through intestine due to its ability to inhibit the disaccharide degrading enzyme. It enhances insulin secretion by stimulating pancreatic islet cells (comparable to Tolbutamide / sulfonyl urea) also increases peripheral glucose uptake, reduces glucogenesis, inhibits release of glucagon, growth hormone and cortisol.
4. Cytotoxicity and anti-mutagenicity action – The aqueous extract of plant shows cytotoxic and anti-proliferative actions. The stem has higher activity than leaf extract. The active component identified is 7β-O-D- di-glycopyranosyl-dihydro-quercitin / iso-cholorgenic acid and several of its analogs which is verified when applied to the  Hep – 2 and A-549 carcinoma cell lines. The methanolic extract of plant also shows potent anti-mutagenic behavior toward Trp – 2 induced mutagenicity or anti-tumor actions against mouse myolema P388 cell line.
5. Anti-ulcerative effect – The alcoholic extract shows anti-ulcer activity in a dose-dependent manner when tested on aspirin ulceration in laboratory rats. The inhibition of Prostaglandin synthesis could be one of the causes.
6. Nootropic effect – The plant extract displays nootropic effect on neonatal and young-adult rats when administered over 30 days showing significant increment of Acetylcholine level in the hippocampus which is liable for short term, long term and spatial memory that helps navigation ability and cognitive senses.
7. Anti-microbial effect – The active componenet liable for anti-microbial and antifungal effect has been identified which is particularly Isochlorogenic acid analogs. It also inhibits HIV infection.
8. Miscellaneous effects – A) Anti-epileptic effect; B) Anti-seizure effect; C) Anxiolytic effect; D) Hypolipidemic effect; E) Diuretic effect; F) Anti-spasmodic effect. 

Other uses: Due to large abubdance in many regions around the world and harmlessnes, it is often used as cattle feed. Its further uniqueness involve in removing heavy metals from the waste water system which is a great privilage for natural way of cleaning the water supply.

Elaeocarpus Ganitrus / Rudraksha / রুদ্রাক্ষ

General features: It is large and fast growing (~ 4 years to maturity) evergreen tree, normally raised under tropical weather of Gangetic plains, foothills of Himalayas and in other South East Asian nations also in Australia, Guam and Hawaii. The tree is considered holy to all the Hindus. The word ‘Rudraksha’ signifies to be the tear drop of Lord Shiva (“Rudra” meaning Lord Shiva and “Aksha” meaning ‘Tear drop’. The botanical name is Elaeocarpus ganitrus. The species exists in many forms and E. ganitrus is one of them, so is the appearances of various natures of Rudraksha. The plant belongs to Elaeocarpaceae family. As per morphological characteristics, the tree can reach to a height of 70 – 200 ft high that depends on the region and subsequent climatic conditions. The diameter of main trunk is ~ 4 ft which is almost cylindrical with grayish appearance of the bark. The large leaves look almost like mangos, which is ~7 inches long and 1 – 1.5 inches wide. The leaves are shiny bright green on the upper side but dull leathery look underneath. The flowers are white with fringed petals appearing around the months of April or May. The leaf cycle stays all around the year. The fruits start growing from June and ripe within August to October. The fruits are spherical in shape with blue color when ripened having hard seed inside. The dried seeds are considered as holy beads which often have different faces, called ‘Mukhis’. The most common ones have five faces or ‘Mukhis’. But it can grow from one to twenty one ‘Mukhis’. The rarest one is single Mukhi. The diameter of largest bead is ~ 1.2 inch whereas the averages are ~ 0.4 inch. Regarding the color, beads vary from red, white, brown, yellow and black. The largest growers of Rudraksha are, India, Nepal and Malaysia. Characteristically, Nepalese varieties are somewhat bigger in sizes whereas those from Malaysia are the smallest ones. The Indian types stand in between, but have versatile color and shape that grow approximately all across the country. Among those places, Malabar and Neelgiri hills grow the most.

Mythology behind Elaeocarpus ganitrus / ‘Rudraksha’: Seeds claim to possess distinctive holy features in the route of Hindu religion. As per the myth, they are respected to be propitious, offering numerous benefits including good health also removing away any mortal sins by wearing as necklace made from those beads. Rudra is the Lord Shiva’s Vedic name and in Sanskrit ‘Aksha’ meaning tear-drops. The mythology says that a demon naming ‘Tripurasur’ once gained huge power who then subdued all in the heaven and earth. Even the Gods were grossly intimidated by him. He was savagely slaughtering the innocent people. The Gods lost their power and turned helpless. Later they went to meet Lord Shiva at Kailash and begged for His help. Realizing severe gravity of the situation, Lord Shiva drew His most powerful weapon to destroy Tripurasur. But sensing its limitless destructive power, if unleashed, tears rolled out His eyes realizing the collateral damages. At that time He dipped in deep emotion and tears dropped on the earth. Mother Earth rapidly held it that eventually gave birth as Rudraksha tree. Hindus believe that the beads hold the secrets of evolution about entire cosmos. Lord Shiva always wear that rosary beads on His neck, head and arms. It is a sign of spiritual, religious and materialistic significances. In Puranas, it glorifies the casteless society pointing how the hermit God crosses the line to unify all the human souls irrespective of castes or creeds while showering the blessings to all. It is believed that anyone dies while wearing the Rudraksha will attend ‘Moksha’, the eternal salvation of his soul which would be free and forever out of any sins.

Faith behind the use of Rudraksha: Throughout the India no other trees are mystically as legendary as Rudraksha. Although no direct link has ever been established still it has been a traditional belief that the seeds of this pious tree holds powerful spiritual energy. As per the mythology, Lord Shiva wears the Rudraksha garlands. It is possibly the major reason why mostly the Shivaities are seen to wear the beads. Since Lord Shiva is the male God so for a long period of time it was a tradition that only men are allowed wearing them. Later, changing of religious doctrines permitted its use within the women. It is said that the beads enable to hold the spiritual energy that subsequently helps devotees concentrate in meditation or recite mantras enhancing the spiritual developments of mind. Concerning the belief, those beads are thought to provide protection from the incoming dangers of all spheres. In that regard, different types of Rudraksha have their traditional rulings or meanings which is largely guided by the Hindu astrology. The extent of spiritual use of Rudraksha is unfathomable. Besides any unsupported medical remedies, it has been articulated in many ways that different categories of beads have different psychological effects in mind. Approximately, 1to 21 ‘Mukhi’ types of beads are so far known. According to the Hindu astrological guidelines each one of them is destined to offer separate effect. The number of beads which one can wear is specifically eighty four but that could be divided in garland, wrist or arm band, as viewed in the icon of Lord Shiva.

Ethnomedicinal role: Plenty of medicinal uses are noticed from the very ancient times regarding the use of extracts of E. ganitrus plant. The pharmacological properties involved are anti-inflammatory, anti-depressant, anti-asthmatic, hypoglycemia, anticonvulsant, antiulcerogenic, smooth muscle relaxant and hydrocholeretic (bile enhancer). The extract of seeds, leaves and bark offer large beneficial effects concerning the healing or controlling numerous ailments like, diabetes, acne, tuberculosis, cough, high blood pressure, heart diseases, gastritis, memory loss, indigestion, leucorrhea, hemorrhoids, insomnia, cancers, prostate enlargement, arthritis and impotency and several others. Traditionally, it is a common faith that just by wearing the beads can help protect from various illnesses due to its electromagnetic role. But exact scientific facts remain unfounded. The fruits have thermogenic and sedative role which are effective against bronchitis, anorexia, migraine, neuralgia and cephalagia.

Chemical components: The analysis of ethanolic extract identifies the presence of alkaloids, phenolics, flavonoids, glycosides, saponins and oils. The phenolic content is 232 mg and flavonoid is 91.5 mg per gram of fresh green fruit. Among the alkaloids, the major ones, which are isolated from the leaves are, Elaeocarpine, Isoelaocarpine and Elaocarpidine, Epi-iso-elaocarpiline, Epi-allocarpiline, Allo-elaeocarpiline, Pseudo-epi-iso-elaocarpiline, Rudrakine, Elaeokine A, B, C, D, E, Elaeocanidine A, Grandisines C, D, E, F & G, Isoelaoecarpiline, Elaeocarpidine, 15, 16 dihydro-elaeocarpine, 15, 16 dihydro-elaeocarpine, Elaeocarpenine, Iso-elaeocarpicine, Isoelaocarpine, Elaeocarpine. Almost all of the alkaloids isolated from E ganitrus have Indolizidine moiety that interact with the human δ₁ – Opioid receptors with varying but significantly high affinity (IC₅₀ ~ 2 – 30 µM). They are largely responsible for exerting analgesic effects. δ₁ – receptors are mostly expressed in the basal ganglia and neocortical regions of brain. They also potentiate µ – Opiate receptor action in brain. It is effective on chronic pain and anti-nociceptions.

Rudraksha oil: It is now extracted mainly by following the process of cold pressing using the seeds. The oil is used for dietary supplement. It is often used as hair oil which can remove dandruff acting also as conditioner. If applied on face, it reduces acne and pimples also acting as a skin pacifier the oil is used to remove ringworm and eczema.

Structure of few Indolizidine alkaloids from Elaeocarpus ganitrus.

Among the major identifiable flavonoids, the notable ones are, Myrcetin, Meamsetin, Meamsetin 3-O- β – D- glucopyranoside, Meamsitrin, Tamarixetin – 3-O-α – rhamnopyranoside, 4`-methylmyricetin, Myricetin 3 – O- Rhamnoside, Quercetin. The major tannins are Gallic and Ellagic acid and their numerous glycosides.

Few flavonoids and tannins from E. ganitrus.

Some of the cytotoxic compounds found in leaves are Cucurbitacin A, D & F which are triterpene hydrocarbons also found in the common vegetable cucumbers. These cytotoxic components are effective against human cancer cells especially for treating oral carcinomas.

The fatty acids detected in E. ganitrus are, Palmitic, Iso-palmitic, palmitic, Oleic, Linoleic, Hexadecanoic and linolenic acids in the fruits. Regarding the extracts of bark the major components are alkaloids, sterols, flavonoids (only when extracted with chloroform), several known terpenoids are noticed in the methanolic extract but no saponins are identified in any of the extraction media whether ethanolic, methanolic, chloroform or in aqueous extract.

Pharmacological effect: The laboratory experiments have verified numerous pharmacological actions of various ways of extracts.

Analgesic, Anti-inflammatory & Anti-ulcerogenic effect – The extraction of seeds and leaves by alcohol or petroleum ether exhibits potent anti-inflammatory and analgesic effects. The experiments on live animals have identified that the underlying reason is due to inhibition of Cyclooxygenase thereby preventing the generation of prostaglandin which leads to exert the analgesic, anti-inflammatory and anti-ulceration effects.

Anti-oxidant effect – The alcoholic extract of E. ganitrus leaves produce strong anti-oxidant effect. Approximately, 500 µg / ml of extract is equivalent to ~ 25 mg ascorbic acid in terms of anti-oxidant capacity. The large presence of phenolics and flavonoids are suspected to be the major cause behind this anti-oxidant action.

Anti-depressant effect – The water-soluble part of dried ethanolic extract of fruits shows strong anti-depressant action. In addition, it can act as cardio-stimulant, smooth muscle relaxant and enhancer of bile secretion by contracting the gall bladder. A part of the effect is mediated via β – adreno receptor activation whereas the other could be due to the direct mucosotropic role. It is also effective to control epilepsy and other mental illnesses.

Anti-hypertensive effect – The aqueous extract of seeds shows anti-hypertensive action by lowering the blood pressure and ischemia in kidneys. The extract possibly influences renin-angiotensin system while controlling the blood pressure. The efficiency is comparable to the drug Captopril.

Anti-asthmatic effect – The ethanol, chloroform or petroleum ether extract of E. ganitrus fruits show significant stabilizing effect on mast cells and bronchial asthma. Experiments conducted on the animals inducing bronchial spasm by spraying aerosol using acetylcholine and histamine show considerable preventing effect by any of those fruit extracts.

Hepatoprotective effect – The use of fruits and leaves extract show significant hepatoprotective actions when orally administered in laboratory animals. The CCl₄ induced liver damage can be prevented efficiently.

Antianxiety effect – The ethanol extract of leaves is seen effective against mentally anxiety as indicated by the laboratory experiments following maze model using mice. The efficiency is comparable to Diazepam. The alkaloid, Tensarin is thought being the active compound.

Anti-malarial and cytotoxic effect – Prolong ethno-pharmacological investigations indicate that the extract of fruits and leaves have in vitro suppressing actions against Plasmodium falciparum (IC₅₀ ~ 0.5 – 8.0 µg / ml). The extract also has strong cytotoxic effect on immortal cervical cancer cell line, HeLa and MRC5 lung fibroblast cells. The effect has been identified due to several Indolizidine alkaloids.

Anti-diabetic action – The antidiabetic effect of E ganitrus fruits is frequently applied as folk medicine which has been evaluated being effective in laboratory animals under both normal and Streptozotcin or Alloxan induced diabetic conditions. The extract exerts hypoglycemia stimulating pancreatic islet cells helping secreting insulin which is comparable to Glimepiride, ~ 20 mg / Kg. If adsorbed on Chitosan the effect of fruit extract becomes highly synergized. Similar effect is noticed in the case of aqueous extract of leaf extract. In all cases growth of pancreatic islet cells and subsequent enhancing role of insulin secretion has been noticed. The action is believed to be due to strong ROS destroying ability of large flavonoid and other anti-oxidant reserve.

Medicinal and Pharmacological effects of Rudraksha

Catharanthus roseus / Rose periwinkle / নয়নতারা

General features: It is a perennial flowering plant commonly known as Rose periwinkle / Madagascar periwinkle which is botanically titled as Catharanthus roseus. The plant belongs to Apocynaceae / ‘dogbane’ family, grown mainly in the warm tropical climate, often claimed to be the native of Madagascar but grows wildly in the tropics of South Asian nations like India, Bangladesh, Pakistan, Thailand, and Indochina including Australia, Spain, USA and parts of mainland China. In Bengali, it is named ‘Nayantara’ (নয়নতারা) meaning ‘eyeball’. Although regarded to be ornamental but the plant earns incredible reputation for its immense medicinal values, particularly being the original source of several multi drug resistance potent anticancer drugs, Vincristine and Vinblastine and equivalent others, also considered to be the large source of Vinca alkaloids having enormous medicinal role. The evergreen shrub / subshrub grows ~ 3.5 feet tall displaying oblong shaped 1.0 – 3.5 inches long and 0.5 – 1.5 inches wide glossy green leaves with short petioles (0.5 – 0.8 inch) which are arranged opposite pairs. The flowers have mixed range of white to pink color with darker pink or red coloration at center. The basal tube is 1-1.5 inches long and the corollas are 1 – 2.0 inches having five petal lobes. The fruits are follicles ~ 1.5 inches long and ~ 0.5 in wide. The plant is now considered as an endangered species.

History and Folk medicinal use:   The plant was at first named Vinca rosea by the famed Swedish botanist Carolus Linnaeus around 1750 which was later renamed as Catharanthus roseus in 1834. In 1922, the US pharmaceutical giant Eli Lilly started to extract this plant in an attempt to find its versatile medicinal ingredients basing on the folk use. In 1958, its anticancer potential was scientifically detected. Besides Eli Lilly, the university researchers from Ontario, Canada also identified the similar effects, killing leukemic white cells in vitro. The attempt to cure Leukemia was initiated at first which afterward led to identify the active anticancer ingredient, Vincristine an alkaloid offering potent anticancer role. It took ~ 900 Kg of dried leaves to produce 1.0 gm of Vincristine. The drug has been approved by FDA in the US for Leukemia and Hodgkin lymphoma therapy around 1961. Besides the well-publicized anticancer therapy, the plant extract is used to treat a large number of diseases: Bacterial infections, Acne, Allergy, Abscesses, Viral infections, Diabetes, High blood pressure, Diarrhea, Malaria, Conjunctivitis, menstrual irregularities and many others. Considering the cancer therapy, besides Leukemia or Hodgkin Lymphoma, the extract shows decent success in treating the Lung cancer, Colon cancer, cervical cancer, Breast cancer, anal cancer, Liver cancer, malignant lymphoma, neuroblastoma, Wilms’ tumor and rhabdomyosarcoma. The alkaloids or plant extract shows number of side effects eg, alopecia, nausea and bone marrow suppression. Europeans used this plant to remove headache and controlling of diabetes which has been noticed also in many South Asian nations like Malaysia and Indochina. It also shows antispasmodic and antihypertensive effects. The plant extract indicates memory enhancing property along with its vasodilating effect. It alleviates vascular dementia and Alzheimer’s disorder. Smoking dry leaves may cause hallucination and lack of coordination. The frequent use of C roseus extract may cause kidney and nerve disorders. As per Ayurvedic medicinal consideration, decoction prepared from stem, roots and leaves are used to treat hypertension, gastro-intestinal problems, diabetes and menstrual disorders and other female sexual problems.

Use of C. roseus uses in different countries for various purposes.

Country	Use
India	Leaf extract is used to treat bee or wasp sting.
Philippines	Leaf extract is used to control diabetes, stomach cramp, menorrhagia, cancers Root extract is used against intestinal parasite, cancers and dysentry.
Madagascar	Leaf extract is used as vomitive. Roots used for purgative, depurative, vermifuge, toothache.
Mauritius	The juice from leaves is used for indigestion and dyspepsia.
West Indies & Nigeria	Used for controlling diabetes.
Cuba & Jamaica	Extract of flower is used for eye wash during infection.
Bahamas	Decoction from flowers is used to control asthma, tuberculosis and flatulence.
Malaysia	Plant extract is used to control diabetes, hypertension, insomnia and cancer.
America	Gargling with extract lessens soar-throat, laryngitis and chest ailment.
Africa	Leaf extract is used for menorrhagia and rheumatic problems.

Chemical components and medicinal effects: The plant possesses carbohydrate, flavonoids, saponins, essential oils and alkaloids. It also produces appreciable quantity of essential oils. The major ingredients within the oil is: Leaf oil contains – Linolenic acid ethyl ester (~44 %), Stearic acid (~11 %), Phytol (~ 7%), Hexadecanoic acid (~7%) whereas the oil from flower contains – Limonene (~34%), phytol (~30%) and Linolenic acid ethyl ester (~14%).  Among all the known components of C. roseus, alkaloids produce significant impact for their potent anticancer role to cure or control large categories of cancers. The plant synthesizes large number of various (~ 400) alkaloids of which a significant number are used for the sake of pharmaceuticals, agrochemicals, fragrance, flavor, food additives and pesticides.  Most of the alkaloids of this plant belong to terpene-indole family, often abbreviated as TIA, Terpenoid Indole alkaloid. These are distributed both in aerial parts and roots in versatile ways.

Distribution of various alkaloids in plant

Plant parts	Alkaloids
Plant	Tabersonine, Voafrine, Vindolinine-N-oxide, Vinecaleukoblastine, Ajmalicine, Calmodulin, Isovincoside, Leucristine, Leurosine, Reserpine, Serpentine, Vindoline.
Leaf	Vinecaleukoblastine, Vindolinine-N-oxide, Vindolinine, Leurosine, Deoxy- Vinecaleukoblastine, Vincoline, Zeatin.
Flower	Catharicine, Indole-3-acetic acid, Hirsutidin, Malvidin, Vindolicine, Zeatin.
Root	Ajmalicine, Alsotonine, Carsodine, Leurosivine, Vincaline, Vinsodine, Virosine, Zeatin.

They are synthesized through the secondary metabolic pathways following medium alkalinization, Ca⁺² influx, receptor mediated signaling and oxidative bursts. Their production has been enhanced by the transcription of respective related genes. Further, UV-B causes dimerization of TIA acting as abiotic elicitor. In general, TIA protects against microbial infection and abiotic environmental stresses eg, UV radiation.

The monomeric alkaloids Ajmalicine and Serpentine exert anti-hypertensive effect. Ajmalicine acts as α₁ – adrenergic antagonist with partial recognition to the α₂ – adrenergic receptor imposing anti-hypotensive effect. Serpentine mediates antipsychotic action by interacting with 5-HT2A/C receptor. It also exhibits good anti-oxidant effect and inhibits nuclear translocation of NF – κβ.

The anti-tumor dimeric alkaloids eg, Vincristine and Vinblastine are biosynthesized in the leaves by conjugating with Catharanthine and Vindoline.

The indole alkaloids bear the structure of indole moiety. It is one of the largest classes of alkaloids known so far. About 4100 of them are identified having considerable physiological actions that are often used in different medicines. All are biosynthesized in the plant using the amino acid Tryptophan as their main precursor by using the enzyme tryptophanase or by the intestinal bacteria, Clostridium sporogenes that also produces that enzyme for breaking down the tryptophan. The medicinal properties of many of the alkaloids are known from the time of ancient civilization in India or Aztecs in South America around 1000 BC. The discovery of Indole in 1866 by chemically decomposing the dye, Indigo from plant by Adolf Von Baeyer, a German scientist further initiated the search to find other related compounds.

In C. roseus, the Vinca alkaloids are synthesized in the stem as milky sap which is poisonous by nature. About 0.86% of the alkaloids are located in the root whereas ~ 0.67% in leaves and ~ 0.37% in the stem. Those alkaloids can arrest the proliferation of several cancer cells by binding to the tubulin in mitotic spindle. It also induces apoptosis thereby suppresses the spreading of cancers. Most of the alkaloids from Vinca family are high valued compounds for its immense therapeutic role especially in the treatment of numerous cancers eg, breast, ovary,  lung, colon, rectum, testis, leukemia, Hodgkin’s diseases and neuroblastoma. The compounds are integral part of chemotherapy regimen. Normally, they are administered intravenously. These are effective against multi-drug resistance tumors or cancers. A few important ones are discussed below.

Vinblastine –

The compound is available in sulfate form as white crystalline, water soluble and moderately hygroscopic by nature. Physiologically, it exerts anti-mitotic effect thus widely used to control number of cancers like, breast, non-small cell lung cancer, head and neck cancers, testicular cancers and Hodgkin’s lymphoma. It quite resembles to Vincristine. The drug binds to tubulin and subsequently inhibits the assembly of microtubules thereby preventing the cell cycle particularly at its M phase. The alkaloid can raise the five year survival rate to almost 98%. It combats cancer by interfering with glutamic acid metabolism. It is also useful in treating Kaposi’s sarcoma and breast carcinoma as well. It is very toxic and suppresses bone marrow inducing gastrointestinal toxicity a potent vesicant, causing blisters or extravasation injury and embryo-toxic therefore not prescribed during pregnancy. Breast feeding is barred during treatment with Vinblastine since it is noticed to secrete in the breast milk. Patients having any infections are not prescribed for it.

It is also a mitotic inhibitor, largely used for cancer chemotherapy naming as Oncovin and approved by the FDA in 1963. The compound binds to tubulin dimer thus inhibits the assembly of micro-tubule structure preventing mitosis in metaphase state during the cell cycle. It affects all rapidly dividing cells which particularly includes the cancers but also intestinal epithelial and bone marrow cells. It is delivered intravenously to the patients. Vincristine is often used along with drug regimen like, Doxorubicin, Adriamycin, Cyclophosphamide and Prednisone. Both Vinblastine and Vincristine are employed in sub-micromolar range from 10 nM to 1.0 µM.  In a strange way, over 10 µM concentrations it causes tubulin aggregation rather than disruption. The regimen are frequently administered in the case of acute lymphoblastic leukemia also for the Wilms’ tumor and nephroblastoma. The compound is highly toxic may cause peripheral neuropathy, constipation, hyponatremia and hair loss. The intrathecal administration often causes massive encephalopathy, demyelination of spinal neuron inflicting severe pain which can cause fatality. Occasional lung spasm causing breathing problem might also develop. The use of Vincristine or Vinblastine also induces thrombopenia, leucopenia, motor weakness, psychosis, convulsions, neuropathy and peripheral neuritis. Despite its various adversarial effect, it is still a very effective ingredient in cancer treatment.

Vindesine –

It is also an anti-mitotic alkaloid soluble in water, often used in the chemotherapy for cancers of Leukemia, Lymphoma, melanoma, breast, lung and uterine cancers. Its side effects are almost to others.

It is also an anti-mitotic agent and effective against non-small cell lung and breast cancer. It is also used for other tumor and cancer therapies and possesses less side effects especially on the nervous system. It reduces immunity toward infections causes anemia, diarrhea, hyponatremia, numbness and tingling of hands and feet.

Other therapeutic properties: The extract from plant, leaves, flowers and roots provide numerous health benefits in addition to its powerful anti-tumor actions: A) it can lowers blood glucose level to 50 – 60% due to increased glucose utilization in the liver; B) It has strong anti-microbial actions against Salmonella typhimurium and Pseudomonas aeruginosa; C) Powerful anti-oxidant especially Vindolicine; D) antihelminthic that protects human and cattle; E) Hypotensive, sedative and tranquilizing effect; F) Anti-diarrheal action; G) Hypolipidemic effect, lowering Cholesterol, LDL and VLDL. Below is the diagram for various use of different parts of C. roseus extract.

 

Vitex Negundo / Chaste tree / নিশিন্দা / সিন্দুবার

General features: Vitex Negundo (VN) is an aromatic shrub grown in India and other South East Asian nations, Mediterranean regions also in parts of the central Asia. The whole plant or some of its parts are widely used in the folk medicine for its anti-inflammatory, febrifuge, anti-fungal, anti-oxidant and hepato-protective actions. The plant belongs to Verbenaceae family which is closely related to the Lamiaceae.  It is known as five-leaved Chaste tree which is often termed as Chinese chaste tree. The plant bears different names in India depending on the place of its birth. In Bengal, it is commonly known as Nishinda or Sindubar (নিশিন্দা or সিন্দুবার). The word Nishinda means destined to prevent. The name is directed for its potential preventing ability toward many diseases. Although VN shows immense medicinal potentials still it is much ignored even today. In most of the Indian villages it is normally used for marking the land boundaries. It is found to grow on the roadsides or even in wilderness, considering to be an unwanted plant. It is a medium sized tree about 10 – 25 feet in height having reddish brown bark with five lanceolate leaflets. Each one is 4 – 8 inches in length and the central one is the largest, holding a stalk. The leaflets are toothed and its bottom surface is hairy. The white-bluish flowers are grown in panicles, 4 – 8 inches in length. The petals are different sizes having middle one is the largest. Both corolla and calyx have dense white hairs. The rounded berries / fruits are succulent drupe and 0.2 inch in diameter having black / purple color when ripe.

History behind the use: Throughout India, the plant is considered sacred. As per the legend, it has been originated from the abdomen of Lord Shiva thus often used in His religious formalities. Besides Lord Shiva, the plant and leaves are also offered to Goddess Durga / Gauri during the ritual of Nitya Sambara Brata, performed by many Hindus. Besides religious rites, a few Hindu Puranas mentioned medicinal qualities of the plant. The Vamana Purana considers it being holy plant. Interestingly, the Vedic agricultural treaties written in ancient time by the Saint Kashyapa, recommended preservation of VN seeds to protect this species due to its enormous medicinal potential. Due to Greek influence, the tree captured the name – Chaste tree. Ancient Romans, medieval monks and nuns used its seeds to secure chastity. Historically, the plant has been consumed to reduce the sex drive. It has strong physiologic influence on the reproductive system of both sexes, men and women. The women of Athens used to place the clippings of Chaste tree under the bed during the festival of Ceres for staying virgin and virtuous. It was also used during their puberty rituals / festivals.

Traditional medicinal importance of leaves, roots, barks, fruits and seeds:  A large number of medicinal effects are identified from the use of VN for treating varieties of ailments based on the pharmacological evidences.

Leaves – The dry leaves or its extract possess anti-bacterial, antitumor, febrifuge, sedative, astringent, tonic and vermifuge effect. It reduces the swelling of joints caused by rheumatism also enables to control the gonorrhea and other bacterial infection. The leaf juice can block ulcers and reduce sinus problems. It is effective against intestinal worms and other parasites entered in the body. Uniquely, the leaves have potent mosquito repellant property. In villages, the dry leaves are often burnt with grasses to repel flies and mosquitos.

Fruits – The dried fruit acts as good vermifuge. Considering its healing effect as folk medication, the fruit is used to treat unstable angina, colds, coughs, pain and rheumatic fevers. The dried fruit helps blood circulation in pelvic zone thus acts a good emengogue relieving menstrual or endometrial cramp or pain. It enables to provide good level of breast milk production among the new mothers.

Roots – The root extract acts as good expectorant and febrifuge, potently lowers the body temperature during fever. It is claimed to have the diuretic properties. It can be further used to treat rheumatic problems, colds and hair growth.

Seeds – The dried and powdered seeds are used as pepper substitute thus acting like condiment.

Stem – The decoction prepared from stem is used to treat the burns.

The table shows uses of different parts of VN controlling various illnesses and diseases.

Diseases	Plant part
Diarrhea (gastro-intestinal disorders)	Flowers.
Dysentry	Roots and barks – powder or tincture
Flatulency and irritable bladder	Tincture from whole plant, bark and roots.
Dyspepsia	Root – powder.
Cholera	Flower – extract.
Colic	Roots – powder.
Headache	Leaf – poultice from crushed leaves.
Eye problems / Cataract / Watery eyes,	Fruits – decoction.
Respiratory problems/ cough.	Leaf juice or root decoction.
Common cold / Flu / Sore throat.	Leaf juice.
Whooping cough	Leaf extract / paste
Bronchitis	Root decoction.
Asthma	Root decoction
Sinusitis	Leaf poultice / essential oil of leaves.
Gonorrhea / dysmenorrhea / uterine dysfunction	Whole plant juice / leaf or shoot juice.
Galactogogue	Shoot juice / fruits.
Postpartum recovery	Leaf extract in boiling water.
Eczema / Carbuncle / Abscesses / Leprosy	Root powder / Essential oil of leaves.
Burns	Stem decoction
Rheumatism	Root – powder, tincture or bark or fresh leaf juice.
Cancer	Stem bearing flowers, leaves.
Gout	Fresh leaves.
Jaundice / liver disorders	Flowers
Malaria	Roots, whole plant
Wounds and ulcers	Leaf and root decoction
Dentistry	Stem for brushing, leaf decoction for mouthwash
Diuretic	Roots and leaf juice
Tonic	Roots, leaves and flowers
Anti-allergic	Leaves
Pain, backache, bodyache	Analgesic role of leaves and fruit juice
Anti-toxin	Aqueous extract of leaf, bark and root
Anti-feedant / fumigant / Insecticide	Burning dry leaves or spraying fresh leaf extract

Phytochemicals: Analysis of various plant parts reveals large reserve of phytochemicals (~ 120 compounds) in VN which can be categorized in four major classes: flavonoids, terpenoids, lignin and steroids. The fruits from VN also produces number (~ 20) of bioactive phytochemicals which also belong to those category. In addition, certain alkaloids like Nishinadine are also identified but its structure is not yet fully elucidated. The table shows the approximate distribution of phytochemicals within the plant parts.

Nature of compounds	Plant parts
Flavonoids	Leaves, Seeds, Stem bark, Twigs, fruits.
Lignans (Phenylpropanoids, Phenylnapthalene type, Phenylidene type, Furanofuran)	Seeds, Roots, fruits
Terpenoids (Sesquiterpenoids, Diterpenoids, Tritepenoids, Iridoids)	Seeds, Stem bark, fruits.
Steroids	Leaves, Seeds
Coumarin	Seeds, Leaves
Organic acids	Leaves.

Major flavonoids in VN

Major Lignans of VN

Major terpenoids in VN

Iridoids in VN

Streoids in VN

Other bioactive compounds

Composition of essential oil of VN

The major components of essential oils extracted from the leaf, flower and dry fruits are given below. Strong antibacterial actions are displayed by each of the extract in addition to other properties.

Leaf – p-cymene, cis-Ocemene (~ 3%), Citronellol (~2.3%), β – Caryophyllene (~ 5%), α – Guaiene (~1%), δ – Guaiene (~18%), Caryophyllene epoxide (~10%), Valencene (~2%), Ethyl-9-hexadecenoate (~29%).

Flower – n-heptane (~5%), β – Caryophyllene (~5%), Valencene (~2%), α- selinene (~17%), Germacren-4-ol (~9%), Caryophyllene epoxide (~15%), E-nerolidol (~8%).

Dry fruit – α- Copaene (~5%), β – Caryophyllene (~5%), α – cedrene (~14%), α – Guaiene (~2%), α – Humelene (~4%), Aristolene (~8%), Germacren D (~8%), β- selinene (22%), Caryophyllene oxide (~3%, n-hexadecanoic acid (~8%), Plamitoleic acid (~3%).

Pharmacological effects: The synthesis of varieties of phytochemicals makes VN a very potent medicinal herb. Regarding the pharmacological effects, previous attentions are focused concerning its role on anti-inflammatory, anti-nociceptive, anti-oxidant, anti-tumor, insecticidal, antimicrobial, anti-androgenic, anti-osteoporotic, hepato-protective and anti-hyperglycemic actions.

Anti-inflammatory and anti-nociceptive effect: The extract of seeds or fresh leaf from VN provides good remedy toward pain and inflammation including rheumatoid arthritis. Leaf extract behaves as peripheral analgesic and regarding the anti-nociception effect, components of leaf do not work via any opiate receptors instead inhibit Prostaglandin (PG) synthesis, follow anti-histamine action, membrane stabilization or effective through its anti-oxidant role as established by the experiments. The anti-nociceptive effect is majorly noticed in the seed extract. The compound (48) of lignan family, as shown below is identified to be largely responsible for the anti-nociception effect. It also creates potent analgesic and anti-inflammatory actions. Another strong anti-inflammatory compound, 3,4- di-hydroxy benzoic acid has been identified also in the leaf. In laboratory rat models using Freund’s complete adjuvant induced arthritis the VN extract significantly lowers the levels of inflammatory cytokines, TNF-α, IL-1β and IL-6 but enhances the anti-inflammatory cytokine IL-10. Additionally, down regulation of COX-1 and 5-LOX in the animal serum are also noticed. On that perspective, VN extract can be utilized to treat the rheumatoid arthritis. A large number of anti-inflammatory compounds are identified in the extract as shown below. Each of them acts in different way(s) eg, Anguside and Iridoid glycoside suppresses the formation of Leukotriene B₄ and few other inflammatory cytokines work by balancing the act of T cell mediated, T_h2 humoral immune response and T_h1 helper cell mediated response. The compounds Vitexdoin D, E & F are the excellent NO inhibitors (IC₅₀ ~ 0.11 to 0.15 µM). Additionally, there are other labdane type bicyclic di-terpenoids (75 & 78) which are Negundoin C & E (75 & 78) displaying potent anti-inflammatory actions inhibiting NO production by blocking the expression of iNOS along with the production of Prostaglandins.

Major anti-inflammatory and anti-nociceptive compounds in VN

Anti-tumor effect: A large number of compounds from various parts of VN extract belonging to the family of lignan, flavonoid and terpenes have been identified to have the anti-tumor role toward breast, prostate, liver and cervical cancers by working via down-regulating the Bcl-2/ Bax ratio and activating caspases. A mixture of lignans naming EVn-50 from the extract of VN seed fraction shows anti-tumor property following those pathways. It is seen that the compound (48), 6-hydroxy-4 (4-hydroxy-3methoxyphenyl)-3-hydroxy-methyl-7-methoxy-3,4-dihydro-2-napthaldehyde induces apoptosis by inhibiting the enzyme, poly ADP ribose polymerase also by decreasing Bcl-2/Bax ratio within the prostate, breast and ovarian cancer cells. EVn-50 exerts cytotoxicity on carcinomas by arresting the cell cycle at G2/M phase thereafter inducing apoptosis. It shows strong effect on human ovarian cancer cells xenografted in nude mice. The compound Casticin, a flavonoid isolated from VN exhibits cytotoxicity toward hormone dependent human prostate cancer cell line LNCaP and human lung cancer carcinoma Lu1 (IC₅₀ ~ 0.5 and 0.8 µg / ml). Research further establishes that highly hydroxylated flavonoids, Chrysoplenetin and Chrysoplenol induce cytotoxicity toward human epithelial pancreatic cell line PNC-1 (IC₅₀ ~ 0.12 µg/ ml) and lung carcinoma NCI-H522 (IC₅₀ ~ 0.18 µg/ ml), human hormone independent highly metastatic prostate cancer cell line PC3 (IC₅₀ ~ 0.17 µg/ ml) and human ovarian cancer cell line OVCAR-3 (IC₅₀ ~ 0.18 µg/ ml). Some of the highly effective compounds within the lignan family are identified to be Vitedoin A, B & C that inhibit DNA synthesis within the human cervical cancer cell line, Hela cells (IC₅₀ ~ 0.13 µg / ml). Several Sesquiterpenoids like Negunferol (66) and tri-terpenoid like Negundonorin (83) are found to possess anti-cancer property toward the human leukemia cell line, HL- 60 (IC₅₀ ~ 0.94 µg/ ml). The Negundonorin has potent cytotoxicity toward human breast cancer carcinoma, ZR-7530 (IC₅₀ ~ 0.55 µg/ ml). Obviously, the VN extract has shown potential role in controlling cancers in human.

Anti-oxidant effect: It is widely known that oxidation plays dominant role in the human aging process also insists developing innumerable diseases. The seeds of VN possess considerable anti-oxidant actions against lipid peroxidation.

Anti-oxidant compounds in VN

It has been noticed that the compounds, Isofraxidin and previously mentioned 6,-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydroxymethyl-7-methoxy. 3,4-dihydro-2-naphthaldehyde, Vitrofolal E, Vitrofolal F, detetrahydroconicrin,Negunidin B and (+)-lyoniresinol have strong anti-oxidant properties. About six potential antioxidants are isolated from the seed extract. The compound Negundin B from the root extract can also inhibit lipoxygenase enzyme. In that way it may be helpful to inhibit the progression of inflammable diseases like arthritis or even cancers. Several other lignans from the root extract also express different medicinal properties in addition to its anti-oxidant effect. (+) – Lyoniresinol is seen to have very potent inhibitory effect against tyrosinase activity. Eventually, it becomes the lead molecule recently to develop the drugs to treat hyperpigmentation. The essential oil from VN acts both as antioxidant and inhibitor of melanogenesis (preventing melanin pigment generation in skin) therefore it is a potential ingredient to be considered for the skin care cosmetics.

Anti-androgenic activity: The flavonoid rich fraction of seed extract shows anti-androgenic effect on male reproductive system which is the underlying reason for its use as a medicine for male contraception. The administration of Flavin rich fraction interrupts spermatogenesis also reduces protein, RNA and sialic acid synthesis in testes and epididymides reducing androgen production. Experiments on laboratory animals confirmed that it has significant interfering role on male reproductive system lowering the sperm count, motility as well as reduction of testosterone production. One of the major mechanisms is its ability to inhibit the enzyme androgen synthetase, AKR1C3 the key steroidogenic enzyme involved in the pathway of testosterone synthesis. The fraction is now under consideration to treat the prostate cancer since it also express anti-prostate cancer activity.

Anti-osteoporotic actions: It is noticed that few components of VN display phyto-estrogen like behavior which can be utilized to control osteoporotic disorders. Until now, the identifiable compounds in leaves are Anguside, Negundoside and Luteolin which show osteogenic action by enhancing osteoblast differentiation and mineralization also. The other one isolated from the seed extract is Vitexdoin F.

Ant-osteoporotic compounds in VN

The lignan, Vitexdoin F inhibits NO production by downregulating the enzyme, iNOS also simultaneously exerts stimulatory effect on the proliferation of osteogenic cell line UMR106 along with its alkaline phosphatase activity. Further, it upregulates the OPG / RANKL ratio considerably. Intertrochanteric fractures (Hip and thigh bone joint) are commonly noticed among the elderly people. Osteoblasts and osteoclasts are regulated by the receptor activated NF-κβ ligand (RANKL) and Osteoprotegerin (OPG) during modeling and remodeling of bone. In that way the serum level of the ratio OPG/ RANKL is important during the healing. The RANKL / OPG system is the signaling pathway which involved in the differentiation and function of osteoblasts and osteoclasts. RANKL is a cytokine synthesized and secreted by the osteoblasts to promote bone resorption. Following the binding of RANKL, OPG inhibits bone resorption caused by the osteoclasts and increases bone formation. So, the compound has a large potential for treating rheumatic arthritis due to its strong anti-inflammatory and anti-osteoporotic role.

Hepato-protective effect: It has been noticed that VN seed extract can prevent liver damage significantly in experimental animals treated with CCl₄ or CH₃CSNH₂. The compound, Negundoside which is an Iridoid glycoside is identified to be responsible for that beneficial role.

It has protective role on human hepatic cells by regulating Ca⁺² homeostasis along with decreasing the generation of reactive oxygen species (ROS) including the peroxidation of lipids.

Anti-hyperglycemic effect: It was noticed that VN leaf extract lowers blood glucose level. The compounds identified are 1, 2-di-substituted idopyranose (100) and Negundoside. Experiments using streptozotcin induced diabetes rats, indicate that the previous compound (100) possibly works by following several ways eg, providing protection to hepatocytes, nephrocytes and pancreatic β – cells while blocking the NF-κβ and iNOS mediated inflammation. Whereas Negundoside might regulate the action of carbohydrate metabolic enzymes and other glycoproteins.

Anti-cataract effect: Cataract formation is largely caused by the oxidative reaction of lens proteins in eye. The VN leaf extract shows good therapeutic potential in preventing the cataract formation in selenite induced rat pups. The flavonoid fraction has been identified to be the protective ingredients enabling to reduce oxidative stress for its strong anti-oxidant effect while maintain calcium homeostasis also protecting the sulfhydryl groups (-SH) from its oxidation within lens proteins.

Antimicrobial effect: VN extracts of various parts using different solvents show different anti-microbial activities. The major components are flavonoids or saponins. The methanolic extract from leaves work against enteric bacteria (Vibrio cholera, Vibrio parahemolyticus, Vibrio mimicus, E. coli, Shigella spps. and Aeronomas spps.) within the intestine of infected infant mice using the doses of 1 – 2 mg /ml. It is also active against few plant fungus also like in soybean pathogens inhibiting the growth. Vitegnoside and Negundoside showed strong anti-fungal activity against Trichophyton mentagraophytes and Cryptococcus neoformans. The crude root extract also shows anti-filarial activities so considered as a candidate for treating lymphatic filariasis. The methanolic extract can prevent motility of Brugia malayi, microfilariae within 48 hours of administration (IC₅₀ ~ 82 ng / ml). The major components are saponins and flavonoids and possibly acting via the oxidative stress. The essential oil of seeds and leaves of VN also exhibit broad spectrum antimicrobial actions. The essential oil of seeds has n-hexadecanoic acid (~17.7%), eudesm-4(14)-en-11-ol (~12.4%) and Caryophyllene oxide ~10.8%). The oil shows considerable antifungal activity against C. albicans at ~ 40 µg / ml). Additionally few antifungal compounds are also isolated from the VN seeds which can potently acts against C. albicans, C. neoformans, Tricophyton rubrum and Aspergillus fumigatus. One is Negudoal (71) a labdane di-terpenoid actually a mixture of diastereoisomers. Further a good number of lignans are also identified to act against those fungal infections. They are Vitelignin A, 4 – Oxosesamin (57) and 4 – Oxopaulownin (62) and the doses are ranging from ~ 16 – 64 µg / ml.

Anti-microbial compounds in VN

 

Miscellaneous effects: The various extracts and essential oils from numerous parts of VN show potent insecticidal property against various flies and mosquitoes carrying number of parasitic diseases. Further, the extract from seeds shows strong immune stimulating behavior and two of the active compounds have been identified. One is 6-hydroxy-4(4-hydroxy-3methoxyphenyl)-3-hydroxymethyl-7-methoxy-3, 4 dihydro-2-napthaldehyde (48) and stigmast-4-en-6β-ol-3-one (111).

The alcoholic extract of leaves show strong anti-histaminic effect by inhibiting the release of histamine from the mast cells. The root extract has anti-ulcerative effect when tested in the laboratory animals along with anti-colitis role. Extract by n-butanol shows strong antitussive effect. The compound Vitrofolal E, a lignan has been identified that can inhibit butyl-choline esterase thus could be effective against Alzheimer disorders. Additionally, the seed extract can control asthma.

Butea monosperma / পলাশ

General features: The plant belongs to the species, Butea which is a native of Indian Subcontinent including the nations like Nepal, Sri Lanka, Vietnam, Bangladesh, Cambodia, Malaysia, Indonesia, and Thailand, Laos and Myanmar also several other tropical regions of South East Asia. The botanical name is Butea monosperma and in Bengali, it is called ‘পলাশ’ subsequently the flower is named after it, ‘পলাশ ফুল’. It is counted as a blessed tree being a treasure from the God. The sacred utensils for Puja (worshipping for deity) are made from its wood. The Butea flowers are commonly offered to the Goddesses Saraswati or Kali. The woods are frequently used in Yagnas (holy offering to fire in the name of deity for the furthering of humanity) during the Puja for any deity according to the rituals of Hindus. The dyes prepared from flowers are sprinkled during the Hindu festival ‘Holi’ in spring. Due to blazing scarlet-orange color of the flowers, it has been nicknamed as Flame of the forest. Hindus believe that it is a gift from Agnidev, the God of Fire. The plant is a deciduous tree shedding leaves in the dry season. It reaches to the height of ~ 50 feet on maturity, but the growth is extremely slow (~ 1ft / year). The leaves are pinnate (feather like arrangement) having 3.5 – 6.3 inches petiole, holding three leaflets. Each one of them is 4 – 8 inches long. The flaming scarlet orange flowers (~ 1inch long) are grown in racemes of ~ 6 inches in length. The fruit pod 7 – 8 inches long and 1.5 – 2.0 inches wide. In most of the South East Asian nations, particularly in and around the West Bengal in India it appears during spring. The tree gained its name after John Stuart, 3^rd Earl of Bute (1713 – 1792), first prime minister from the Scotland in Britain during King George III. This English noble man was the patron of botanical science. The name, Butea was later validated in 1802 by the Royal Society after his death. The plant can grow in water logged swampy or poorly drained soils and even in barren but not arid land. The soil condition should be alkaline. The plant belongs to the pea family of Fabaceae and a genus of the traditional flowering plant. It hosts Lac insect secreting lacquer used in polishing the wood surfaces. In West Bengal and its adjoining regions Butea / Palash (পলাশ) appears in the spring displaying its adorable flaming scarlet-orange color. The famous Bengali poet laureate Rabindra Nath Tagore even composed few poems illuminating the beauty of Palash comparing with passionate colorful love. It is a vital ingredient of spring celebration in Shantiniketan (Tagore’s residence). As per the mythology, Butea / পলাশ is the favorite flower of Hindu Goddess Saraswati (Goddess of Knowledge and learning). In that regard, it is an essential component of Her Puja (worshipping) in the spring.

Folk medicinal use: Butea monosperma is an ornamental tree. It displays vibrant scarlet-orange flowers in spring. Besides exhibiting colorful décor in the garden, this plant has been recommended over the centuries for maintaining good health using as a tonic and treating several liver disorders. It is claimed to have large beneficial role in preventing osteoporosis. Several compounds analogous to isoflavone synthesized within the plant eg, Cajenin, Cladrin, Isoformonoetin and Medicarpin exert strong bone promoting growth whose efficiency is identical to estrogen although Cajenin and Cladrin have no estrogenic property. Among them, only Medicarpin shows minor estrogenic effect. All of them enable to prevent complete bone losses associated with the menopause. In reality, every part of the plant is employed as traditional medicine for treating or preventing various ailments which has been authorized in the past by Ayurveda, the millennia old apothecary of India. The most widely used component is its flowers, which finds useful to treat inflammation of livers or even in case of virally infected hepatitis. In addition, the flowers show tremendous uses like in treating sexual dysfunction, diuresis, infections, and arthritis. The ethanolic extract acts as aphrodisiac and has anti-estrogenic role. It is also used as a general tonic. The extract of leaves are used to treat cough, diabetes, intestinal worms, menstrual problems, piles, CNS disorders, treatment of sexual debility, neuropathic and urinary pain. The root extract also finds many uses. It is used for treating filariasis, night blindness, helminthiasis, piles, ulcers and tumors. It also has anti-infection property. The bark or seed extract are usually used as temporary contraceptive preventing fertility.

Chemical components: The extract of any plant part contains chuck full of flavones, isoflavone, triterpenes and phytosterols.

Bark extract – The components in bark extract are; Buteaspermin A & B, Flemmichapparin C, Genistein, Daidzein, Cajanin, Cladrin, Formonontein, Pruretin, Medicarpin, Buteasperminol, Lupeol, Lupeonone and Stigmasterol. This extract has high level of methoxylated flavonoids bearing resemblance to steroidal moiety. The phenolics content is lower than the other plant bark, 8.02 ± 0.05 mg / g in 80 % H₂O + 20 % CH₃OH extract whereas flavonoid level is 1.04 ± 0.0 mg / g.

Major components in Bark extract

Flower extract – The extract of flower contains Butin, Butrin (di-glucoside) along with its isomer Isobutrin (di-glucoside), Liquirtigenin, Santin, chalcones and dihydrochalcones and their respective glycosides. There are few isoflavones like Formononetin, Afromosin, Coreoopsin, Palasitrin and Sulphuresin.

Leaf extract – The extract of leaves contains stigmasterol, nonacosnoic acid, Euphane (triterpenoid) and analogous compounds in addition to various flavonoids. Alcoholic extract (50 %) ~ 16 mg / g of flavonoids. It is higher than methanolic extract (80 %) which contains ~ 6 mg / g of flavonoids content.

Seed extract – It has large reserve of fatty acids which is ~ 11 % by weight. The composition is, oleic ~ 34 %, palmitic ~ 31 %, behenic ~ 14 %, linoleic ~ 8 % and arachidic ~ 7 %. In addition, it has the flavone Butin and its glucosides. The seed has appreciable level of vitamin C.

Pharmacological & medicinal effects: The blessed plant, Butea is medicinally important since many of its parts are pharmacologically useful to treat vast number of ailments. This is why, it is considered as ‘treasure from God’. Below is the pharmacological effects of several of its parts.

Seeds – The oral administration of powdered seeds prevents fertility dose-dependently in female rats which has been established by the animal experiments. The anti-fertility and antiesterogenic effect is also noticed using the ethanolic extract. The active compound has been identified as Butin. The oral consumption of seed powder produced dose-dependent antihelminthic effect, confirmed in experimental sheep. The antidiabetic effect has been noticed which improved the glucose tolerance tremendously reducing the blood glucose level in alloxan treated rats. Besides the antidiabetic role, it also shows hypolipaemic and antiperoxidative effects in non-insulin dependent diabetic rat models. The antimicrobial, antifungal and antibacterial activities are very pronounced in the case of seed oil. The identified active compound is Medicarpin. The seed also contains lectin, naming Butea monosperma agglutinin which has significant agglutinating effect.

Bark – The alcoholic extract shows considerable anti-ovulatory and anti-implantation activities in animal experiments upon oral consumption. Butin has been identified as being the active ingredient in this context. Interestingly, Butin also shows male contraceptive property. The oil extracted from bark shows antifungal, antimicrobial and antibacterial effects. Ethanolic extract shows potent anti-diarrheal actions. The secreted gum from bark also helps preventing chronic diarrhea. The topical application of alcoholic bark extract helps significantly healing different types of wounds. The strong anti-oxidant and inhibition of lipid peroxidation are seemingly the underlying reasons. The existence of stigmasterol in bark extract shows potent regulatory effect in thyroid hormone reducing Tri-iodothyronine (T3), Thyroxin (T4).

Additionally, the extract shows strong hypoglycemic effect in conjunction with stigmasterol by lowering the blood glucose concentration, reducing the activity of hepatic glucose – 6 – phosphatase (G-6-Pase) and subsequently increasing the insulin level in plasma. As per other biochemical effects, there is a decrease in hepatic lipid peroxidation (LPO), increase in Catalase (CAT), Super oxide dismutase (SOD) and glutathione (GSH) actions which indicates its superb anti-oxidative potential. The recent investigation shows that the stem bark extract shows potent osteogenic activity increasing osteoblast proliferation, differentiation as well as mineralization. The identified compounds are Buteaspermin –A, Buteaspermin – B and Buteasperminol. There are several other components (~ 19) which also show osteogenic property to a certain extent.

Leaves – The alcoholic extract shows strong anti-inflammatory response when studied in experimental animals. The identified components are Butrin and Isobutrin. It significantly lowers the secretion of IL-1β, IL- 6, IL- 8, PGE₂ and Metalloproteinases (MMP -1, 2, 9 &10). The production of PGE₂ and secretion of MMPs are completely inhibited. The inhibition of MMPs along with anti-inflammatory actions indicate its anti-aging role on skin.

The ethanolic extract also shows anti-convulsive property owing to the presence of triterpene naming TBM which has been verified by various ways during animal experiments. The isolate compound protects animals from maximum electro-shock, electrical kindling pentylenetetrazole and lithium – pilocarpine induced convulsions but fails in the case of strychnine induced one. Presumably, the rise of GABA along with the level of serotonin could be the underlying cause behind this anti-convulsion effect. The compound also shows anti-depressant effect to a certain extent by inhibiting the MAO – A in brain.

The powdered leaf or stem bark, flower and even root of Butea enables to remove Giardiasis, a common intestinal infection created by the protozoa -1 parasite naming Giardia lamblia. About 98 % recovery from the infection has been reported. It enhances phagocytic activity of macrophages also macrophage migration index.

Flowers – The presence of anti-hepatotoxic flavonoids, Butrin and Isobutrin in the extract helps cure and prevent many of the liver disorders showing considerable level of recovery of glutathione and other metabolizing enzymes. In experimental animals, the hepato-protective effects are observed during oxidative stress, in the event of carcinogenesis. It protects from the depletion of detoxification and anti-oxidant enzymes. The prior treatment with alcoholic extract helps maintain the structural integrity of hepatic cells also bringing back the serum concentrations of GOT, GPT, LDH, GGT and their activities at normal level. Additionally, the administration of extract either alcohol or water has the lowering effect on brain serotonin, and circulating corticosterone in the case of experimentally  water immersion stress induced animals. The overall ulcer index is also reduced significantly. The extract also shows anticonvulsive property in experimental animals due to the elevation of serotonin and GABA in brain. The most intriguing effect of aqueous extract of flowers is the anti-tumor effect. It inhibits cell proliferation and arrest in G1 phase while indicating significant reduction of activated Erk1/2 and SAP/JNK also inducing apoptosis thereby causing the death of tumor cells. The extract has been tested on several of the human breast cancer cell lines like, MCF-7 (estrogen receptor positive), MDA-MB-231 (triple negative – estrogen, progesterone & HER2) and MDA-MB-453 (HER2 positive). The efficiency is seen much higher in the case of estrogen dependent MCF-7 cell line indicating its chemoprevention action works via the modulation of estrogen and progesterone receptor imposing apoptotic, anti-angiogenesis and anti-metastatic actions.

Effects	Plant parts
Anti-conception	Seeds
Anti-diabetic	Seeds, Flowers
Anti-helminthic	Seeds
Anti-fertility & Anti-esterogenic.	Flowers, seeds & bark.
Anti-tumor	Flowers
Anti-microbial, Antifungal & Antibacterial.	Bark & Seeds
Anti-diarrheal	Stem and bark
Anti-stress	Flowers
Giardiasis	Stem, Root, Flowers & Leaves.
Radical scavenging Action.	Flowers
Anti-convulsive.	Flowers & Leaves
Anti-inflammatory	Leaves.
Wound healing	Stem Bark
Hema-agglutinating	Seeds.
Liver disorders	Flowers
Thyroid inhibitory, Anti-peroxidative & Hypoglycemic.	Stem bark
Hepato-protective	Flowers

Coca leaf & plant

General features: The plant earns extreme vile reputation around the world due to its natural ability to synthesize the beleaguered addictive drug, Cocaine. Therefore, everyone views the plant as a source of corruption associated with illegal trading, violence and social disturbances. But aside from these disturbing facts and taking away momentarily the thought of being an adversarial component, one would see that it is actually a miracle plant having mindboggling nutritional and medicinal treasure. Further, it is an essential part of many of the South American nations’ necessary cuisine, integrated in daily life. This contentious plant actually provides important medicinal help to the inhabitants of Andes Mountain, also helping establishing the modern society in Bolivia, Ecuador, Colombia and places in Argentina and Peru. Either by chewing or sipping tea made out of this leaves help them combatting the effect of altitude sickness. The practice, still they continue for survival. It is the very reason, the plant turns to be the cash crop in those regions. It is an absolute necessary component in the life of native Andean people. It earns extreme bad rap for illicit production and smuggling of Cocaine by devious traders. But chewing or sipping tea would generate no addiction. The psycho-active alkaloid, Cocaine exists in a very low level (~ 0.3 – 0.7 % of dry mass). This low level alkaloid content serves as a tonic to the native mountain population helping oxygenate the blood matchlessly, energizing them to perform daily the heavy duty chores. The easy extraction of Cocaine by acid-base procedure creates its quick availability enabling to open a vast market to the rampant users during social recreation that often leads to forever addictiveness. The fact has been well established and evidences are all around. The universally popular American drink Coca-Cola once used to add Coca leaf extract (possibly around1880) which drew enormous popularity to be an invigorating drink. It is now replaced by the extract devoid of Cocaine. Sipping Coca leaf tea or chewing the leaves enhances energy level like caffeine. Besides its unrivalled oxygenation role, leaves are enriched with iron, Vitamins A & B, Riboflavin, Phosphorous and Calcium. Some even claims that reason behind the high longevity of Andean mountain people relies on the Coca leaf use.

The plant belongs to the family of Erythroxylacea, flowering tree family, which is native of the South American regions having 242 species and four genera. Among those one of them is Erythroxylum novogranatense, which is also a Coca plant. But the common variety normally produced is Erythroxylum coca which produces cocaine in high level. The plant looks like a Blackthorn bush. It reaches to the height of 7 – 10 ft. The leaves appear opaque, thin and oval shaped but taper at the end. They are approximately 3 – 4 inches long and 0.5 – 1.0 inch wide. The flowers are small and built with five yellowish white petals. The anthers are heart shaped. The pistils are made of three carpels combined and creating three chamber ovary. When matured, the flowers change to red berries. Experiments established that Coca leaf can cure alcoholic hangover. Chewing leaves before drinking prevents body to absorb excessive alcohol. The practice also provides relief to the sufferers from arthritis or any topical pain including helping the victims of pre-menstrual syndrome (PMS). It is highly beneficial during eye surgery for preventing the eye flinching. The leaves are often used in local culinary purposes in making bread, cookies or chocolates (Kuka Xoco) by mixing with the cocoa beans which is delicious as well as beneficial for the medicinal reasons. The leaves are also often added in salads. Coca leaves have significant beneficial role in health. Despite considerable benefits of the leaves, the US department of Homeland Security along with other Western Nations impose strict ban on Coca leaves to enter the countries. So chefs, scientists and even doctors are not allowed to conduct any research to develop any medicines from it. Even it is a beneficial food but the easy isolation ability of Cocaine keeps the use far away. Its legal boundary exists within few Andean Mountainous nations where it is a cash crop and a necessary food. It is cultivated on the slopes of Andean Mountain. Therefore ~ 98 % of global productions are bordered within the countries like Colombia, Peru, Bolivia and a part of Argentina. Few regions of Argentina and even Mexico also legally grow Coca to a certain extent. As per its cultivation, the seeds are sown within the months of December to January and raised under shades keeping away from the direct sunlight. The plant grows best in damp and hot climate. The average life of best quality plants are ~ 40 yrs. afterward, it would not produce much good quality leaves. So often re-plantations are sought. The major harvest of fresh leaves is conducted in the month of March.

History of Coca use: Historically, the use of Coca leaf within Andean natives has been noticed around ~ 3000 BC which is evidenced from the artifacts and mummies unearthed from pre-Colombian graves. Coca was an important material within pre-Colombian culture. Besides the large trade value as a cash crop, it is used as medicine, aphrodisiac and ritual inebriant. It was also often sacrificed during the auspicious occasions to Gods. The natives believe that Coca sets link between God and human providing them the individual divinity as well. It is burnt as incense, worn for ritual adornment also smoked on that behalf. In normal social gatherings, the Andean natives chew Coca leaves. The practice is still continuing. It is thus a part of the social interaction. The ancient healers often used Coca leaves to retrieve souls of ill people asking help from the God. By offering leaves, they believe that God will bring back the original spirit inside the body of those sufferers. To the ignorant Spanish intruders around ~ 1560 AD in South America, typically, it was a complete voodoo. The Spanish Inquisition declared the native rituals as witchcraft. So out of contempt, they banned and suppressed the use. The natives totally disregard the ban since it is a necessary ingredient for survival at this oxygen poor high mountain region.  In recent days, the use of Coca leaves has been legalized among the natives in Peru, Bolivia and several South American nations of the Andean regions. Considering the mythology, Andean Tukano Indians believe that the plant grew out of the finger joint of the daughter of lord of all living creatures. In that accord, all varieties of Coca plants are the siblings, so they should be taken good care. The Tukano males spend about three hours a day to prepare Coca powder which every tribe consumes keeping them productive and subsequently suppressing the hunger. It is their firm belief that Coca protects the body removing away any dark spirit. Seemingly, the plant appeared in the Europe around 1570 – 1580 AD. About two centuries later, the isolation of Cocaine was successfully performed by a German chemist naming Albert Niemann in 1859 AD. At the end of nineteenth century, cigars and cigarettes rolled out of Coca leaves were sweeping all over the Western European nations including the east coast of America. Around 1864, a French chemist, Ange-Francois Mariani / Angelo Mariani produced a sweet wine, ‘Vin Mariani’ using the Coca extract which became highly appreciated throughout the Europe earning awards and accolades from the European elites like, Queen Victoria and even Pope Leo XIII. The wine turned out to be hugely popular that eventually gave birth a galaxy of intellectuals in Europe for example, Alexander Dumas, Henrik Ibsen, Jules Verne, H.G. Wells and Thomas Edison in the US. The famed nineteenth century French intellectual, Octave Mirbeau thought it as the energy from Goddess. Vin Mariani was actually the precursor of Coca-Cola, where extract of Coca leaf was punched with the extract of Kola nuts providing caffeine for being an energy drink. In recent days, adding Coca leaf extract having cocaine is legally prohibited to use in Coca-Cola.

History behind bad rap for coca leaf use: In 1722, Father Antonio Julian, a Jesuit priest of Spain wrote a book “Perla De America” where he mentioned the merits of Coca leaf and recommended highly to all the Europeans as an alternatives to coffee or tea because of the beneficial effects on health. Later around 1793, Spanish physician naming, Don Pedro Rolasco published an article praising the benefits of Coca and recommended it for the Spanish sailors. Long afterward, around nineteenth century by the efforts of German scientists and physicians Coca was highlighted further within the European community due to its invigorating actions enhancing the overall metabolism of body. The isolation of embattled alkaloid, Cocaine in 1859 by Professor Albert Niemann of Gottingen identified the central reason behind the stimulating efficacy of coca leaf. But that did not bring any taint on its reputation for use at that time. On the other hand, isolation of Cocaine became the most delightful saga for the drug titan, Park Davis to seek for a large market. Around 1880, company brought in the market a vast array of health products containing pure Cocaine eg, mouth wash, gargles, candies, tablets, sprays and ointments. The legendary, Sigmund Freud soon became its devotee. He also wrote an article “On Coca” in 1884. Along with its reputation, Coca leaf also gained controversies due to the presence of Cocaine even at very low and harmless level. The existence of other beneficial ingredients like, sizeable reserve of antioxidants, vitamins, calcium and iron was very much willfully ignored. Its tremendous medicinal ability without inflicting any side effects to control blood glucose and preventing ability toward obesity is totally snubbed. In a very shrewd way, an American pharmacist naming Asa Griggs Chandler of Atlanta, Georgia filed a patent in 1891 for a drink naming ‘Coca-Cola’ adding isolated Cocaine from the Coca leaf and a blast of caffeine from Kola nuts. Essentially, he followed the example of Vin Mariani and its popularity. The drink earned huge popularity by hooking up the people all over the US while using the Cocaine. Everyone in the US from physicians to musicians or scientists embraced the drink. Eventually, its popularity soared limitlessly. But in 1906, the company withdrew Cocaine from Coca-Cola due to the imposition of US Government’s restriction against using any Cocaine associated products, while defining it as narcotics. The withdrawal of Cocaine did not end the company’s long tie with Coca leaf. It remains the sole user of Coca leaf extract in the US. Coca-Cola legally owns the forever rights of Coca leaf extract. The extract is now prepared by Stepan Company plant which was previously named Maywood Chemical Works in New Jersey, US. As per agreement all the Coca products will go only to Coca-Cola except the extracted Cocaine which is sold to the chemical firm, Mallinckrodt. Stepan is authorized to make Cocaine free Cola leaf extract only for Coca-Cola. So Coca-Cola is the company within US who only uses the unique flavor of Coca leaf. Clearly, it is a shrewd business tricks to establish monopoly over the use of any products made from the Coca leaf. Without the legal approval of Coca-Cola no one would gain the access to use any products of Coca leaf. It is the only company who is allowed to import any Coca leaf cultivated in Peru under its supervision. In that way, Coca-Cola is the sole authority of Coca leaves in US but not outside. But through heavy lobbying in the US Congress, the US government pressurized other nations through the UN not to cultivate any Coca plant by declaring it as a narcotic. In recent days several South American nations vigorously opposed the act since that plant is a necessary factor for their survival. Due to strong opposition the bans are lifted in some specified places especially in Bolivia where the parliament and its president unanimously opposed it. The president of Bolivia is himself an Andean native and also a Coca farmer. Without the permission of Coca-Cola no Coca leaf could be imported to US even for the purpose of medicinal research. The company is holding its perfect monopoly just by advertising and advocating the adversarial effects of Cocaine.

Popular medicinal use: Coca leaf often is used as an important folk medicine throughout the South American nations especially within the Andean natives to maintain health and fitness. It is widely used even today to treat different types of pain, rheumatism, cold, flu, digestive problems including constipation, colic, upset stomach, exhaustion, altitude sickness, and weakness also for assisting while in the labor. Additionally, the dry leaves are smoked to help bronchitis, cough and asthma sufferers. The tea made out of Coca leaf reduces diabetic problems, suppresses appetite, helping reduce the body weight for obese persons. It provides help due to the altitude and travel sicknesses.

Alkaloid content, chemistry and traditional effects: On an average, Coca leaves contain 0.5 – 2.5 % alkaloid which are mainly Cocaine, Cuscohygrine or Hygrine. In addition to the major ones it synthesizes several others which are Methyl-Ecgonine-cinnamate, Benzoyl-Ecgonine, Truxilline, Hydroxy-tropococaine, Tropococaine and Nicotine. A few are metabolites originated from the cocaine and pharmacologically inactive.  Regarding the chemical nature, Cocaine is a tropane alkaloid whereas Hygrine and Cuscohygrine are alkaloids of pyrrolidone moiety. All of them exert euphoric effect. Studies indicate that Bolivian and Peruvian Coca leaves contain highest level of Cocaine as also the total alkaloids content. In addition to alkaloids, the leaf possesses significant level of flavonoids, tannins, essential oil, terpenes, vitamins A, B and C and numerous minerals particularly Calcium and Iron. About 100 g of leaves can provide adequate amount or the daily recommended dose of vitamins and minerals. For this reason, it is claimed to be a super food and by all means it is included in the regular diet of the Andean indigenous population. Interestingly, both fresh and dried leaves hold almost identical food values. The adequate consumption per day balances appropriate sugar level in circulating plasma also maintaining the normal blood pressure. It uniquely regulates the blood oxygen level improving its absorption in the body due to thin air at high altitude of the mountain.

The biosynthesis of tropane alkaloids is extensively studied in different plant systems including Erythroxylum coca, the actual coca plant. It has been identified that the tropane ring has been bio-synthesized from the amino acid, ornithine. Similar situation arises in the case of pyrrolidone alkaloid, Hygrine and Cuscohygrine as well as the Nicotine which is derived from ornithine and nicotinic acid. Below is the biosynthetic pathway for several alkaloids of Coca plant.

The compound Hygrine – α – carboxylic acid is further metabolized to produce cocaine, Ecgonine, methyl Ecgonine, benzyl-Ecgonine, isomers of Truxilline and others.  Cocaine has four stereo-specific centers producing sixteen isomers but which one exerts the physiologic effect is exactly unknown. It is a logical assumption that all of them produces the concerted effects.

Bio-synthesis of Cocaine

The leaves act as a good aphrodisiac also significantly suppress the appetite. It is a potent animating compound exerting considerable physiologic stimulation. Due to its euphoric ability, Cocaine earns a bad rap but chewing leaves would not contribute enough level to induce any euphoria. On the other hand, if mixed with Trichocereus cacti, it acts as powerful stimulant that creates strong psychedelic effect. Trichocereus cacti has loads of alkaloids with Phenyl-ethylamine moiety. They are enable to induce hallucinogenic effect like, Mescaline, Anaholidine, Anahaline, Hordenine, Tyramine, 3 – methoxy tyramine etc. Mescaline is a potent psychedelic compound comparable to LSD or Psilocybin (found in several mushrooms). Cocaine released during chewing converts to pharmacologically inactive metabolite Ecgonine, a tropane alkaloid which stays within the body for about seven hours at a very low concentration. Whereas Cocaine itself would retain in the circulation for not more than two hours. Chewing Coca leaf on daily basis do not establish the addiction. The fact has been verified by number of studies. When chewed, it takes few minutes for cocaine and other ingredients to be spread inside the mouth. At that time, the numbness is felt in mucous membrane. The stimulus effect appears within 5 – 10 minutes which later increases with time and thereafter becomes leveled off and afterward quickly goes down within ~ 45 minutes.

 The extracted illicit cocaine use produces euphoria with simultaneous excitation of CNS neurons and local numbness due to its anesthetic role. Afterward it brings depression. The continuous use has a habit-forming effect that eventually leads to the serious drug abuse behavior. It also induces hallucinations and psychotic effect. If contaminated with others like in the case of street cocaine, it creates danger to the mind, spirit and health of the users. Often the overdose produces coma. One should keep in mind that although the Coca leaves produces low level of cocaine but it is not for the sake recreational abuse. It is a folk medicine to the Andean indigenous people thus should be treated with proper respect.

Coca leaf by itself does not induce any dependence or abstinence even after the prolong use. Due to this non-addictive property, use of Coca leaf is a suggested method for helping the recovering cocaine addicts. In recent days the herbicide, Glyphosphate (synthesized by Monsanto) resistant Coca plant, Boliviana negra has been created by the Bolivian farmers to protect their cash crop by following natural process of selective breeding. It is for their survival to fight against the Coca eradication campaign by aerial spraying of Glyphosphate conducted by the US and Colombian army for repressing the indigenous population.

Glyphosphate inhibits the enzymes which are involved in the synthesis of Tyrosine, Tryptophan and Phenylalanine thus effective only to prevent the active growth. It is absorbed via foliage later transported to the growing places to block the specific amino acid synthesis. Although widely used as a weed killer and Monsanto’s claim to be physiologically ineffective toward the human is not true. Many studies indicated the fact being opposite. The compound is a suspected cancer causing agent provoking Non-Hodgkin’s’ Lymphoma.

Effect of Cocaine on brain / CNS: Action of Cocaine is primarily relayed via the action of Dopamine in brain. During regular neural communication, the released Dopamine from a neuron within synaptic space binds with its targeted receptors situated on a neighboring neuron. In this way, Dopamine acts as a chemical messenger propagating signal within the neuronal network. Whereas the other protein, Dopamine transporter removes away excess / unused Dopamine from that synaptic space by recycling back to the former neuron for further use. The use of Cocaine intervene this normal communication process by binding with the Dopamine transporter protein thereby preventing Dopamine’s reuptake from the synaptic gap. So, the excessive accumulation of Dopamine within synaptic space heavily amplifies the signal of the receiving neurons. As a result, the event creates euphoria and stimulation usually felt right after taking the Cocaine. The entire effect lasts for not more than an hour (t_1/2 ~ 10 mins). Besides inducing the euphoria, small doses often make energetic, mentally alert as well as talkative. Additionally, they turn hypersensitive to light, sound and touch. Temporarily it also deprives sleep and lowers the food intake. It helps perform physical and mental tasks with ease although some feel the opposite.

On the other hand, the repeated use of Cocaine brings long lasting changes in the brain. The change is observed within Nucleus Accumbens (NA). Its continuous use leads to neuroadaptations while releasing significant amount of excitatory neurotransmitter, Glutamate that eventually disrupts the overall Glutamate transmission system including the level of its receptor, which is the reward pathway located within NA. The glutamate system is responsible for reward pathway. Often anti-addiction medicines target it to block that pathway, the event of neuroadaptation. Further, its continuous use also develops stress. Since brain starts to adapt so the reward pathway turns less sensitive whereas neural circuits involved in stress become over sensitive expressing intense level of displeasure often bringing violence or negative moods if not taking any Cocaine. This is a classic withdrawal symptom. Under this situation the abuser desperately looks after cocaine showing complete disregard toward any relationship, food or social norms and rewards. On the other hand, the release of stress hormone by cocaine also helps acquiring the neuroadaptation. Stress usually contributes to the relapse, simultaneously disorders created by cocaine also create stress-related disorders. Further due to frequent use, tolerance is developed so higher doses are more and more needed to experience similar level of drug induced pleasure. Eventually, the tolerance leads to the toxicity imposing over dosing which often brings fatality. The stress circuits are distinctly different from reward pathway but they too often overlap. The Ventral tegmental area (VTA) acts as the integration site relaying information about both stress and signal for Cocaine to other brain sites even the one searching for it. It has been experimentally verified that repeated users always look for it in case of stress. The more they use that produces more stress eventually affecting the behavior.

Other physiologic effects of Cocaine: The major effects that are produced due to the intake of Cocaine are, constriction of blood vessels, pupil dilation, rise of body temperature, increase of heart rate and blood pressure. Administering the high dose at a time often leads to erratic and violent behavior. The users might also feel abdominal pain, restlessness, anxiety, vertigo, tremor, panic, paranoia and muscle twitching. The additional reported medical complications are arrhythmia, heart attacks, strokes, severe headaches and coma. The combination of alcohol and Cocaine makes the situation deadly because of the formation of Cocaethylene inside the body which is ethyl ester of Cocaine. The compound potentiates effects imposed by the cocaine.

Pharmacological effects of Cocaine related components in Coca leaf: These compounds behave like Cocaine to a certain extent but devoid of few other effects.

Benzoyl-Ecgonine – It is a major metabolite of Cocaine. But unlike Cocaine, it does not show anesthetic property but exerts potent stimulus action. It blocks the Dopamine reuptake by its transporter thus behave in many aspects like Cocaine.

Methyl-Ecgonine – It also shows no anesthetic effect but prevents Dopamine reuptake by binding to the transporter.

Pseudotropine – It does not show any behavior of atropine.

Benzoyltropine – It has strong cholinolytic action but showing no anesthetic effect. It is an antagonist of Serotonin also inhibits Dopamine and Nor-epinephrine uptake in cortex and striatum.

Tropacocaine – It has same anesthetic effect like Cocaine but possesses much less toxicity. It also prevents Dopamine and Nor-epinephrine uptake in cortex and striatum.

Cuscohygrine – It inhibits delayed type hypersensitivity.

Hygrine – It shows no anesthetic role unlike Cocaine but possesses some of its role.

Conclusion: The restriction imposed behind the use of Coca leaves is not just for the Cocaine which is nothing but an eye wash. It is mainly for the sake of protecting the monopoly business right of Coca-Cola. The plant possesses enormous medicinal virtues which is extremely beneficial for the human health.

Syzygium Cumini Skeels / Jambolan / Black plum / Jamun / Jambul / কালো জাম।

General features: The botanical name is Syzygium Cumini Skeel often nick named as Jambolan. In India, it is called Jamun or Jambul (Hindi) and Kalo Jam / কালো জাম (Bengali), meaning ‘black berry’ which is a misnomer to actual black berry. It is an evergreen tropical large flowering plant belonging to Myrtaceae family, originally a native of India / Andaman / Ceylon but also grows in various other regions of the subcontinent particularly in the far South East Asian nations. Syzygium Cumini also grows in Hawaii and South American tropical countries. The plant is spread by the Indian emigrants in the Caribbean islands like in Trinidad, Tobago, Guyana and even Queensland in Australia. The tree can reach more than ~ 100 ft. high. The stem is often greater than ~ 5 ft. diameter. It reaches full size in ~ 40 years. The lower bark appears discolored and coarse. The branches are gray-white. The leaves have light turpentine smell which are arranged in opposite ways. As per shape, they is elliptic, oblong and glossy green providing leathery feeling by touch; ~ 5 in long and ~ 1in wide with short pointed tips. The midrib within leaf is very prominent and yellowish, showing closely parallel lateral veins. The flowers are small white or occasionally pink, ~ 0.5 inch long growing in clusters with 4 petals fused in a cap offering nice fragrant smell. The fruits are grown in clusters of 20 – 40 in numbers, shaped ovoid and appears like berry ~ 1.0 inch long that grows in bunch with shiny dark purple appearance. In some species, the fruits are white. The berries have single seed inside. The unripen fruits are green but as they mature, it then change color, at first becoming pink then crimson red and finally attains to shiny black or deep purple. The fruiting season in India is around May or June. The fruits / berries taste delicious, a combination of sweet with a tinge of sour with touch of added astringency. When eaten, it makes the tongue purple. The woods from stems are water resistant therefore used in India for making railway sleepers or other outdoor needs. It is very hard and heavy. The tree grows all over India from the Himalayas down to Southern plain. The birds are highly fond of this berry. It is heavily loaded with anti-oxidants, vitamins and minerals thus extraordinarily beneficial for human health. Since Vedic period, the bark, leaves, trunks and fruits are therapeutically used for the sake of preventing or curing many common ailments.

History: The Hindu epic, Ramayana indicates that during fourteen years of exile in the forest, Lord Ram often survived on this fruit (Jambul). To many North Indian Hindus, it is thus considered as the ‘fruits from God’. Its fresh leaves are often used in many regions for decorations during the wedding as a sign of auspiciousness. Further, according to the Hindu mythology, Lord Krishna chose His own body color after observing the shiny bright appearance of Jambul. So, it is often seen to be planted near the Krishna temple. In many South East Asian nations, the tree is highly revered which is seen even among the Buddhists. For centuries, the tree is normally planted in the orchards for getting fruits and timber.

Use as folk medicine: Since it grows all over the tropics around world, so people are habitually using it as a folk medicine besides consuming as foods. Undoubtedly the fruits are extremely delicious and in addition it provides large quantities of minerals, fibers and anti-oxidants. All parts of the Jambolan plant, fruits, seeds, barks, leaves and stems have medicinal role. Among those applications, preventing or controlling diabetes is very common around the world. Aqueous decoction made from the fresh green matured leaves (~ 2.5 g / L) is often used to treat diabetes by the people of Southern Brazil. In India, the fruit juice or aqueous bark extract or even the mixing together is offered to cure or prevent the diabetes. In Maharashtra, the west coastal state of India, this same mixture is administered to increase appetite and preventing dysentery. It is also used to cure digestion disorders, bowel spasms, and flatulence and stomach problems. The seed extract is externally applied to cure sores and ulcers on skin. It is also used to cure dysentery, constipation and pancreas problems. In many regions of India, it is prescribed also against mental depression, nervous disorders including exhaustion. The leaf extract has strong anti-inflammatory role which can reduce the swelling of gum and removing bacteria in mouth. It is often orally administered as an antidote in the case of opium overdose or poisonous insect bites. The tasty ripen fruit juice is good for people with chronic gastric problem and women facing the problem of multiple abortions. It can cure chronic lung problems like asthma or bronchitis. According to the village apothecaries (Kaviraj) in India, Jambolan fruit and seed has the aphrodisiac effect.

Phytochemicals: The fruits, leaves, stems and barks of Jambolan plant are highly enriched with anthocyanins, Ellagic acid, Isoquercetin, Kaempherol and Myrcetin along with several of their glucosides. Additionally, the seeds contain Jambosine and glycosides like Jambolin and Antimellin. Some of them prevents breaking down of starch to sugar. The extract of seed are hugely fortified with numerous flavonoids which are widely known antioxidants enable to scavenge endogenously generated free radicals and reactive oxygen species, therefore beneficial to the health. On the other hand, the presence of Ellagic acid lowers the blood pressure significantly (~ 35 %). It is an undeniable fact that most parts of the tree is loaded with phenolics and anti-oxidants although at different levels. The fruit is fairly rich in protein, minerals and vitamins particularly Vitamin C. Approximately, 100 g of fruit flesh contains Na – 26.2 mg, K – 55.0 mg, P – 16.0 mg, Ca – 15.0 mg, fiber – 14.0 g, protein – 0.7 g, Mg – 35.0 mg, S – 13.0 mg, Fe – 1.6 mg, Cu – o.3 mg, Folic acid – 3.0 mg, riboflavin – 0.01 mg, Vitamin A – 8.1 IU, ascorbic acid – 18.0 mg.

Leaves –  The fresh leaves contain Quercitin, Myrcetin, Myrcetin 3 – O – 4-acetyl – L- rhamnopyranoside, triterpenoids, tannin and enzymes like, esterase and  Galloyl – carboxylase.

Stem bark – It is enriched with Betulinic acid, Friedelin, Epi-friedelanol, β – Sitosterol, Eugenin and fatty acid ester of Epi-friedelanol, β – sitosterol, Quercitin, Kaempferol, Myrcetin, Gallic acid, Ellagic acid, Bergenins, flavonoids and tannins. The presence of Gallic acid, Ellagic acid and tannins provides astringency in syrup produces from the bark.

Roots – It is rich with flavonoid glycosides and Iso-harmetin – 3 –O- rutenoside.

Flowers – It contains Kaempferol, Quercitin, Myrcetin and their glycosides and galactosides, also Myrcetin – 3 – 1-arabinoside, di-hydro-myrcetin, Eugenol-triterpenoid A, Eugenol-triterpenoid B and Acetyl – oleanolic acid.

Fruits – Fruits contain high level of raffinose, glucose, fructose, citric acid, mallic acid, gallic acid and anthocyanins. It also synthesizes Delphindin – 3 – gentibioside, malvidin – 3 – laminaribioside, petunidin – 3 – gentibiose, cyanidine diglycoside, and free petunidin and malvidin. The astringency is owing to the presence of gallic acid whereas the color is produced by the anthocyanins.

Essential oil – Each parts of the Jambolan tree produces significant amount of oil out of that ~ 80 % is essential oil by nature. The major components are α – Pinene, β – Pinene, Camphene, Myrcene, Limonene, cis – Ocemene, trans – Ocemene, γ – Terpinene, Terpinoline, Bornyl acetate, α – Copaene, β – Caryophyllene, α – Humelene, γ – Cadinene, δ – Cadinene, β – Selinene, β – Myrcene, cis – farnesol, Linoleic acid, Malvalic acid, Sterculic acid and Vernolic acid.

Below is the structure of few commonly available anthocyanin, generated in the form of reactive cation. In plant, they undergo naturally linked with the glycosides providing varieties of color in fruits, flowers and leaves. The methoxy (CH₃O -) group gets linked by the enzyme catechol – O-methyl transferase.

Structure of few important phyto-chemicals in Syzygium Cumini – fruits, flowers, leaves, barks and stems

Phyto-chemicals	Physiological effects of few phyto-components from Jambolan
Kaempferol	Flavonoid, Strong anti-oxidant, powerful anti-cancer agent by inhibiting phosphatidyl Inositol kinase thus inhibiting neoplastic transformation.
Oleanolic acid	Exhibits antitumor, antiviral, anti-HIV, Anti-HCV effects, hepato-protective works by Inducing γ – IFN.
β – sitosterol	Strong antitumor agent, Induces apoptosis while activating caspases in human breast cancers and other tumor cells.
Eugenin	Iso-coumarin / chromone, Immune modulator, immune suppressive flavone, antibacterial, anti-inflammatory by inhibiting COX – 1 & 2, cytotoxic to human breast cancer (MCF-7), colon cancer (HT-29) and lung cancer (A-549) cells.
Gallic acid	Anti-tumor agent by inducing apoptosis in numerous human cancer cells including Prostate and cervical cancers, strong anti-oxidant, prevents tumor growth by decreasing Cyclin B1 and E also prevents amyloid protein synthesis thus protecting from dementia And any neuro-degenerative diseases.
Betulinic acid	Tri-terpene pentacyclic, strong anti-inflammatory, anti-HIV, anti-neoplastic induces apoptosis, inhibits DNA topoisomerase, inhibits human metastatic melanoma by increasing p53.
Friedelin	Tri-terpene pentacyclic, anti-inflammatory by inhibiting TNF – α secretion.
Epi-friedelanol	Pentacyclic tri-terpene, anti-microbial, induces apoptosis in human cervical cancer cells, Anti-osteoclastogenic.
Quercitin	Flavonoid, strong anti-oxidant, prevents lipid peroxidation thus lowering the Cardio-vascular diseases, anticancer, helping patients suffering from the inflammation Of prostate, prevents viral infections, helping asthma patients, suffering from ulcers, Gout and chronic fatigue syndrome also possesses chemo-preventive role.
Ellagic acid	Di-lactone, strong anti-oxidant, powerful anti-cancer compound particularly inhibits Carcinogen binding to DNA.
Myrcetin	Flavonoid, anti-oxidant, anti-carcinogenic effect, anti-viral action, anti-thrombotic, Anti-diabetic effect, anti-atherosclerotic action, neuro-protectant, anti-inflammatory, Anti-platelet aggregation activity.
Anthocyanidins	See separately below.

Anthocyanidins: Like any naturally synthesized colors, the color of Jambolan fruit is owing to the synthesis of anthocyanin pigments occurring in glycosylated form. In Jambolan fruits, the anthocyanidins (Delphindin, Petunidin, Malvidin, Cyanidin etc) are synthesized at very high level. Its stability depends on the medium pH. It is stable at the acidic range but undergoes color change under basic or neutral condition for ionic molecular structure, the flavylium cation. In acidic pH, they display red but with increasing pH to neutral or basic condition it gains purple or blue coloration. Due to cationic nature, anthocyanins are soluble in the water. The reaction with tannin and subsequent polymerization stabilizes the anthocyanin moiety along with protecting the color. Besides dsiplaying color, those compounds exert fabulous beneficial role on health, proven by the scientific studies following both in vivo and in vitro models. It employs large number of biological actions offering positive impacts on each human subject. They are powerful anti-oxidant as well as strong microbial by the nature. All of them help improve neurological health simultaneously protecting individuals from numerous non-communicable diseaeses. The protective role follows multiple and different pathways eg, following free radical scavenging, blocking cyclooxygenase (COX – 1 & 2) enzymes, mitogen activated protein kinase signaling pathway or preventing inflammtory cytokines generation. Additionally, they produce good impact on chronic diabetic sufferers by lowering the serum glucose level. Before the advent of insulin, it was perhaps the best  treatment for diabetes.

Medicinal and pharmacological effects: Below is various pharmacological effects produced by the extracts of Jmabolan plant parts.

 

Interestingly the extracts of Jambolan leaf provides protection against radiation damage. Additionally, the alcoholic seed extract offers potent role against anxiety disorders, psychotic disorders, sleep disorders and eating behavior. The reaction causing lipid peroxidation and subsequent adversarial effect on cardio-vascular tissues can be prevented by the fruits pulp and seed extract.

Cannabis / Marijuana / Hashish /গাঁজা / ভাঙ্

General features: Cannabis is perhaps the most debatable herb ordinarily known as marijuana or hashish all around the globe. It enables to exert impermanent psychotic or euphoric effect that entices a great many people particularly the youths to use it for recreational purposes. In Bengal, it is titled as Ganja (গাঁজা) or Bhang (ভাঙ্). Approximately, ~ 4 % of the entire global population falling in the ranges of 15 – 64 years of age have used it in few occasions in their life time for the sake of enjoyment. Interestingly, that percentage remains unchanged even today. The world’s net legal production is ~ 70,000 kg / year. Cannabis or cannabinoid is counted as narcotics and a contraband product in many countries. The presence of tetra-hydro cannabinol (THC) and its various analogs are identified to be the psychoactive agents produced inside the plant. Pharmacological studies exploring its numerous physiologic functions provide wealth of information that leads to synthesize significant number of compounds which are prescribed as necessary medicines used for anti-inflammatory, analgesic, anti-psychotic and numerous other indelible diseases. The plant belongs to Cannabaceae family which fits in the genus of flowering plants. Majorly, three species of this genus naturally occur, which are Cannabis Sativa, Cannabis Indica and Cannabis Ruderalis. Cannabis Indica and Cannabis Ruderalis are occasionally considered to be the subspecies of Cannabis Sativa. All of them are the native of Indian subcontinent and Central Asia. The plant grows in sunny and temperate climatic condition thus often seen in many tropical and subtropical regions of the world. The flowering tops of plants secrete a resinous psychoactive compound commonly called cannabinoids that possesses the actual psychoactive ingredients. In recent days, some of its derivatives are used for numerous medicinal purposes. Cannabis is a fast growing annual plant. It earns maturity within 2 – 4 months under sunny and temperate condition. Cannabis Sativa grows ~ 15ft high whereas Cannabis Indica reaches only ~ 6ft in height and the other one is about the same. The plant is dioecious by nature meaning to exist in both sexes of male and female. They produce different types of flowers. The male flowers produce pollen which synthesize least amount of THC whereas the female ones are loaded with the psychoactive compounds. Several monoecious type is also known. In this category, the individual plant bears both male and female flowers botanically termed as hermaphrodite. In normal cases, female plant blooms large resin-secreting flowers. Although male plants pollinate the females initiating the seed production but the flowers which are normally consumed are the seedless females (Sinsemilla), enriched with cannabinoids including THC. The hermaphrodites or self-pollinated type produces less seedless Sinsemilla thus have a low level of cannabinoids.

As per the plant anatomy, region called Bract holds the female reproductive part looking like green tear shaped leaves which are excessively surrounded by the resin glands producing highest level of cannabinoids. Calyx is a translucent layer over the ovules situated at the base of flower. The Trichomes appear to be clear bulbous globe that offers protection to the plant against any predators. They secrete aromatic oil containing terpenes, and cannabinoids including THC and CBD. The leaves of Cannabis Sativa, Cannabis Indica and Cannabis Ruderalis are somewhat different by the appearance. For example, in Cannabis Sativa the leaves are long and slender (> 7 inches long) having pockmarks and rough edges displaying lime green. Its large leaf contains at least 13 leaflets.

But for Cannabis Indica, the leaves are slight wider, stocky also shorter in size and have few leaflets about 7 – 9. They are deep olive green in color. The fading green coloration if appears that would signify the sign of malnourishment. For Cannabis Ruderalis, the leaves are shorter and having 5 – 7 leaflets. Its overall look is close to Cannabis Indica but the color of leaves are less green.

Hindu mythology behind cannabis use: The medicinal use of cannabis has been extensively mentioned in Atharvaveda around ~ 2000 BC which is considered as being the earliest information revealed in history. According to the Vedas, cannabis is a source of joy and happiness which is offered to the human to lose fear and attaining delight also to remove away the anxiety. Its use in the Hindu mythology is wide spread which gives impetus to many for its use but that practice ends up as abuse. Interestingly, the use is associated with the worshipping of Lord Shiva, the hermit or nomadic hippie God scantily dressed riding on a bull who is also the sole protector and destroyer of universe, often indulged Himself in its use either by smoking Ganja (dried leaves) or eating or drinking with sweets (Bhang). The myth says that, Lord Shiva after a domestic quarrel with his wife, Parvathi left home and went inside a forest for cooling down and rest. While resting, he fell asleep under the shade of a large banyan tree. Right after waking up, He noticed beautiful plants before Him. Being curious, He chewed few leaves that provided Him extreme joy, divine pleasure and mental relaxation removing away any anxiety and anger. From then on, He included those leaves as a favorite entity for daily use. To the Hindus, cannabis is considered as a sacred plant.

Different ways of using cannabis

Forms	Source	Ways of use / abuse
Marijuana / Charas / Ganja	Dry leaves, flowers and stems	Smoking as joint
Bhang	Fresh leaves and stems	Making foods for oral use.
Hashish / oil	Leaves, stems and flowers	Smoked as joint.

Cannabis use in other religions: Buddhism does not encourage the use of cannabis. It is considered to be an intoxicating agent that hinders meditation also clouding the mental awareness. Whereas Sufis during 13^th century used cannabis for many spiritual contexts. In recent days, besides the Hindus the use of cannabis is seen only among the Sufis (particular sect preaching the mystical / spiritual representation of Islam religion) around the world especially in Pakistan, India, Turkey and Indonesia during the annual festival named Urs which usually falls on Thursday evening. Further, in old Nordic culture, Freya the love goddess of Norse often used it for enchantment as well as to enhance her pleasantness and sexual behavior. In recent days, the Rastafari movement (Jamaican variety of Christianity originated from Ethiopia) has included cannabis as a divine rite. In addition to the Rastafarian some Christian sects also use cannabis as a sacrament.

History of cannabis use: Around ~ 2000 BC or earlier, the euphoric / ecstatic property of cannabis was identified at first in India. It was recommended at the then time by the ancient apothecaries for medicinal reasons to reduce fever, inducing sleep, relieving headaches, curing venereal diseases and stimulating the appetite. About the same time (2000 – 2700 BC), the medicinal practice of cannabis was also noticed among the Chinese. They used the herb in treating rheumatic pain, malaria, constipation or female menstrual disorders. Besides the medicinal role, cannabis plants or hemp (colloquial name for non-medicinal cannabis) are employed to make ropes by the ancient Chinese, Greeks and Romans which they used for their naval purposes. The hemp rope is extremely sturdy and not easily ruptured by any natural course. Hemp is categorized as inferior grade cannabis plants which are used for the industrial and commercial reasons like, rope making, fiber or textile for weaving to produce garments. Some of the hemp products are also utilized for the preparation of food and drinks. Hemp oil from cannabis seeds are used in making oil soluble paints, creams or moisturizing agents or even spent for the cooking of foods. Hemp seeds are quite identical to flax seeds which is used as bird or animal feed. The medicinal use of cannabis was introduced in the western nations in the middle of nineteenth century (~ 1840 AD) by a British army physician, Major W. B. Shaughnessy while serving the British Indian army in India. He went through large pile of millennia old Indian medical literature and arrived at the conclusion that cannabis is a safe drug for use. Before prescribing to the human he conducted extensive experiments on various animals like rats, mice or rabbits to observe any adverse effects particularly concerning the mortality. The herb did not kill anyone even at significantly high doses. So, he started prescribing to the patients experiencing seizures, rabies, rheumatism, fevers and tetanus. In that act, he recorded the anti-convulsive, analgesic, anti-anxiety and anti-emetic role of cannabis. Through his efforts, cannabis became an acceptable medicine in England and other European nations. With the arrival of twentieth century, the medicinal use of cannabis becomes slowly disappeared due to the advent of various synthetic drugs. Further, the fear of cannabis associated with possible addiction made it forbidden to cultivate in the United States and some European nations. Although its illegal use as a recreational drug remains very rampant everywhere. Strangely, in recent days about thirty states within US along with the neighboring Canada have legalized its use and cultivation.

Chemical components of cannabis: Cannabis plants produce large group of terpeno-phenolic compounds which enable to induce euphoria normally experienced after consuming marijuana. Approximately 480 compounds are identified in this herb of which nearly 85 different cannabinoid components have been so far isolated and characterized. Actually, cannabinoids are named only for those C-21 compounds which are synthesized within the plant including the transformed products and related analogs. Among them, only three compounds are seen to exist at the highest level, which are cannabinol (CBN), cannabidiol (CBD) and Δ⁹ – tetra-hydro-cannabinol (Δ⁹ – THC). Interestingly, Δ⁹ – THC is identified to be the only psychoactive component. In majority instances CBD and Δ⁹ – THC are the majorly available products. The existence of CB is very low and like CBD, it has no psychoactive role.

Major ingredients of cannabis

 

Psychoactive compounds	Biological effects
Δ9 – tetra-hydro-cannabinol (Δ9 – THC)	Major psychoactive component exerting psychological and Behavioral effects.
Δ8– tetra-hydro-cannabinol	Less potent in psycho-activity than Δ9 – THC.
Cannabinol (CBN)	Much less psychoactive than Δ9 – THC.
11 – hydroxyl – Δ9 – THC (11 – OH – Δ8 – THC)	Reason for psychological effects of cannabis.
Anandamide (endo-cannabinoids) (Arachidonyl-ethanol – Amide)	Identical to Δ9 – THC action and other cannabinoids that interact with cannabinoid receptors.
Non-psychoactive compounds	Biological effects
Cannabidiol (CBD)	No psychoactive role but exerts anticonvulsant effect.
Cannabichromene ((-) Δ8 – THC -11- oic acid).	Only analgesic action but no psychoactive role.

Interestingly, the physiologic action of Δ⁹ – THC is highly stereo-selective. The (-) – trans isomer is seen much (≥ 100 times) potent than (+) – trans isomer. The presence of Δ⁸ – THC, a positional isomer is also seen to be effective but with less potency. Each plant produces two types of cannabinoids. For that reason, they are characterized according to their chemical phenotype / chemotype depending on the ratio of Δ⁹ – THC / CBD synthesized within them, which is seen to remain constant throughout the plant life. It is definitely genetically determined although environmental factor has a large impact. There are some non-drug plants which have very low level of THC but high level of CBD. Obviously the major drug-plants does the opposite by synthesizing high level of Δ⁹ – THC and low amount of CBD. Often the two phenotypes cross-pollinate. In that case the first Filial (F₁) generation creates an intermediate while synthesizing median level of both. The female variety of this phenotype generates enough Δ⁹ – THC for which it could be regarded as drug producing plant therefore utilized for the drug productions. Some of the plants are seen to produce as high as 20 % Δ⁹ – THC. In recent days, many genetically modified plants have been developed for much larger synthesis of Δ⁹ – THC.

Structure activity relation and pharmacologic behavior concerning Δ⁹ – THC: The strong analgesic behavior of Δ⁹ – THC as a natural product and large content of non-steroidal compounds create colossal interest in the field of pharmacology.  Extensive studies regarding the structure-activity relationship using numerous cannabinoid analogs have confirmed strict stereo-chemical requirement to exert any pharmacological effects. In fact, this information points out actual possibility for the existence of specific cannabis receptors. In the case of Δ⁹ – THC, it is initially speculated that there are three points of attachment needed to interact with the receptor for exerting any pharmacological actions. Those are comprised of A) phenolic group, B) proper substituent at C9 and C) a lipophilic side chain. With the idea of three point attachment and necessary involvement of dibenzo-pyran ring and lipophilic tail a few derivatives were synthesized showing strong analgesic property. One of them is CP – 55,940 (Pfizer) showing identical property like Δ⁹ – THC, even having ~ 50 times potent analgesic effect. Initially it was not counted to be in the category of cannabinoids. But the studies afterwards have proven that it acts as an agonist toward the cannabinoid receptors (CB₁, CB₂ & CB₃) which can be blocked specifically by the CB₁ receptor blocker acting as inverse agonist, Rimonabant (anti-obesity drug). Both CB₁ and CB₂ are the classic G-protein coupled receptor (GPCR) having seven transmembrane strands spanning the cell surface membrane bilayer.  CP – 55,940 is a complete agonist showing high affinities, K_i ~ 0.58 nM toward CB₁ and ~ 0.68 nM for the CB₂. The compound also acts as an agonist toward the CB₃ (called GPR55 / orphan receptor family, activated by Δ⁹ – THC, mostly found in liver). The compound, CP-55,940 provides neuro-protective effect by blocking the intracellular release of Ca⁺² causing subsequent death of hippocampal cells during excessive exposure of N-methyl – d – aspartate (NMDA). On the other hand it induces death in cultured mouse neuroblastoma cell line, NG108-15. Further, it protects brain mitochondria from the poisoning effect of paraquat (N, N`- dimethyl – 4 – 4`- bipyridinium dichloride). Another bicyclic compound structurally differed from Δ⁹ – THC is Pravadoline, a non-steroidal anti-inflammatory agent with high analgesic property. Pravadoline does not work via any opiate receptors but produces powerful anti-nociception action. The compound inhibits the enzyme, cyclooxygenase (COX) thus blocking the pathway for generating pro-inflammatory molecules while producing strong analgesic effects. It is also an agonist toward the CB₁ and CB₂ receptors imposing anti-nociceptive actions. Concerning anti-nociception action, another cannabinoid has been synthesized, Win 55,212 -2 (Pfizer) which also behaves like Δ⁹ – THC.

Win 55,212-2 is characterized as amino-alkyl-indole derivative. Despite having somewhat different structure, its action is identical to Δ⁹ – THC. It is a potent cannabinoid agonist acting as powerful analgesic thereby reducing the neuropathic pain. It also prevents cognitive impairment and the loss of neuronal markers. Like the naturally produced Δ⁹ – THC, it induces strong anti-inflammatory response via the receptors preventing microglial activation which elicits the neuronal inflammation. Δ⁹ – THC can fully eliminate the neurotoxicity caused during microglial activation. On the other hand in some cases Win 55,212-2 is seen to impair memory function and network connectivity in the brain. The compound has higher affinity toward CB₁ (K_i ~ 1.9 nM) compared to Δ⁹ – THC (K_i ~ 41 nM) while acting as agonist. Another synthetic cannabinoid agonist is JWH – 015 (Pfizer). The compound also shows high affinity toward CB₂ (K_i ~ 14 nM) than the CB₁ (K_i ~ 380 nM). Besides having anti-inflammatory or analgesic effects, JWH – 015 displays strong immunomodulatory role.

Cannabinoid receptors and physiological interaction with cannabinoids and endogenous cannabinoids (ECBs): Until now three types of cannabinoid receptors, CB₁, CB₂ and CB₃ are identified, of which the first two are the major ones located mainly on nervous system. Their discovery provides enormous information about the physiological role of cannabinoids. Further, the finding of endogenous ligand like anandamide, Arachidonyl-ethanolamine and 2- Arachidonyl-glycerol categorized as endo-cannabinoids (ECBs) came into limelight which enhances further interests about the role of cannabis on health and diseases. The ECBs are lipid based neurotransmitters which bind to the cannabinoid receptors that are expressed normally all over the central nervous system plus brain including the peripheral nerve tissues. The ECBs are generated as per necessity especially when triggered by the increase of intracellular Ca⁺² at the post-synaptic sites in response to sustaining synaptic actions. Advantageously, ECBs are rapidly metabolized after the reuptake. They are the derivatives of arachidonic acid like Arachidonyl-ethanol amine (AEA), 2- Arachidonyl glycerol (2-AG) and anandamide and act as endogenous agonists to the receptors particularly to the CB₁ and CB₂ displaying high affinities (K_i ~ 80 nM to 300 nM). The ECBs regulate varieties of physiological and cognitive senses, also enables to cross the blood brain barrier. Additionally, it has the role on fertility, pregnancy, appetite, mood, pain sensation, memory and pre and post-natal development. ECBs also mediate euphoria, locomotor activity, attention, and reward processes. For example, the level of anandamide soars up during physical exercise modulating motivational salience or exercised induced euphoria.

As per the CB₁ receptor, it is by far the most abundant G-protein coupled receptor (GPCR) within CNS, expressing at much high level within neo-cortex, hippocampus, basal ganglia, cerebellum and brainstem. It also exists on peripheral nervous system and further on non-neuronal sites like testis, eye, spleen and vascular endothelium. The receptors are heavily expressed at the presynaptic and axonal compartments. It is directed to bind naturally synthesized ligand Δ⁹ – THC which mediates the physiologic effects. The receptor, CB₁ also binds with several synthetic mimetics like CP55940, WIN 55,212-2, JWH -015 and ECBs acting as complete agonists. The CB₁ receptor is linked to the Pertussis toxin sensitive inhibitory G_{i /o} protein. Thus agonist activation leads to the lowering of intracellular generation of cAMP via the inhibition of adenylate cyclase. CB₁ is quite abundant in CNS having the major duty to maintain synaptic plasticity and neural transmitter release. When activated by the agonists, it sends three very different spatio-temporal waves. The initial one is transient (~ 10 mins) is caused by the activation of G proteins whereas the second wave (> 5 mins) is mediated via β – arrestins. The third and last wave takes place at intracellular compartments which may arise either by the G proteins or arrestins. Further, CB₁ shows constitutive activity, an indication of G protein activation without the presence of any agonists. This effect can be reversed by the binding of inverse agonist AR141716A, commercially named Rimonabant often used as anti-obesity medication.

In comparison to CB₁, CB₂ shows more defined localization inside the brain expressing largely within the cells and tissues associated with the immune system. It exists in microglia (resident macrophages of CNS) and its expression is allied with the inflammation. Its localization on microglia is significant since it has important role in Alzheimer’s and other neural diseases connected to the basal ganglia since that controls synaptic functions and involved in the drug abuse. Further, the selective CB₂ agonist JWH133 (K_i ~ 3.4 nM) inhibits dopaminergic firing from the ventral tegmental area reducing cocaine addiction. CB₂ works independently to modulate inhibitory plasticity of the hippocampus. The receptor belongs to the GPCR family and attached with G_{i /o}. Regarding the molecular picture of ligand interaction, it is identified that lipophilic group of agonists interact with F5.46 residue of receptor that allows to form H bond with S3.31 residue imposing conformational alteration triggering the intracellular signaling pathways. Regarding the signaling process exerted by the cannabinoids several data also suggest that the receptors also can activate the G_q leading to the activation of enzyme, phospholipase C that in turn enables to cleave phosphatidyl inositol bi-phosphate (PIP₂) producing inositol triphosphate (IP₃) and diacylglycerol (DAG). IP₃ triggers Ca⁺² release from the internal stores of endoplasmic / sarcoplasmic reticulum whereas alongside DAG activates the protein kinase C. Although few disagree about this pathway suggesting no direct involvement of the cannabinoid receptor. The discovery of high affinity CB₁ antagonist, SR14176A / Rimonabant positively provides evidence of cannabinoids, particularly Δ⁹ – THC which influences the role of other traditional neurotransmitters like dopamine (DA), acetylcholine (Ach), 5-hydroxy tryptamine (5-HT or serotonin), γ – aminobutyric acid (GABA), histamine, norepinephrine (NE), opiate peptides, prostaglandins (PGEs) and its impact on neuropharmacology. Cannabinoids enhance the synthesis of NE, DA and 5 – HT. Cannabinoids also stimulate the release of DA from corpus striatum, nucleus accumbens and prefrontal cortex. The increase of GABA level is also noticed. The major effects of cannabinoids are hypothermia, anti-nociception and change of motor activity. Catalepsy or decline of locomotor action often noticed due to cannabinoids is caused by the release of Ach and its subsequent action on muscarinic and nicotinic receptors and simultaneous release of GABA and its action on GABA_A and GABA_B receptors and PGEs on prostaglandin receptors. Normally, the extrapyramidal system of brain is involved in catalepsy which is further proven by injecting 11- OH- ∆⁸ – THC inside the pyramidal tract. The interaction of ∆⁹ – THC with the neuronal cells within basal ganglia also induces catalepsy. Whereas the incidence of hypothermia by the cannabinoids is mediated by the DA, NE, 5-HT, GABA, Histamine and opiate peptides which is evidenced by the experiments on animals. But the studies on hypothermia are not so consistent therefore unable to pinpoint the exact cause. The event of anti-nociception produced by cannabinoids is highly complex. It is noticed that endogenous neurotransmitters, NE, 5 – HT, ACh, GABA, opiate peptides, PGE1 and PGD2 inhibit the nociception. It is thus a possibility that some of them might interact with cannabinoids to produce the effect of anti-nociception particularly, catecholamines, PGE1, 5 – HT and opiate peptides.

Tolerance and dependence: The pharmacological role of cannabinoids establishing tolerant effect is visualized for both human and primates, rodents, dogs and few others. The tolerance is also noticed in cultured human fibroblast cells when stimulated by the cannabinoids to synthesize PGE2 and arachidonate release including the inhibition of adenylate cyclase activity. But the exact reason behind the development of tolerance remains very much unknown even today. The drug tolerance presumably happens by following the two methods. One is due to changes in pharmacokinetics whereas the other occurs owing to the changes in pharmacodynamics. Evidences indicate that the former which comprises of absorption, metabolism, distribution and excretion plays a minor role. But, the pharmacodynamic events that involves receptor downregulation, conformational alteration of receptor by binding to the agonists and subsequent internalization of ligand receptor complex is possibly the significant cause behind the development of tolerance. Studies indicate that cannabinoid tolerance is partly due to the agonist induced receptor down-regulation. Behavioral tolerance has been observed in case of chronically treated animals which shows decrease in binding in several parts of the brain like limbic forebrain (involved in controlling body temperature, eating, sleeping, emotions and reproductive functions) and striatum (involved in multiple planning and coordination) but contrarily it is enhanced in cerebellum and hippocampus. Convincing evidences exist regarding the development of tolerance toward Δ⁹ – THC in human like that has been noticed in the case of animals. Tolerances are noticed concerning cardiovascular effects, autonomic functions, mood changes, sleep disturbances and intra-ocular pressure when Δ⁹ – THC is orally administered. Whereas the results remain inconclusive regarding any behavioral changes. No behavioral alteration is observed if orally administered for low doses infrequently. A noticeable changes is seen when Δ⁹ – THC is taken at high doses (10 mg) orally for a long period of time. The chronic use of cannabis does not result any severe or significant withdrawal syndrome. But occasional auditory and visual hallucinations along with irritability feelings are reported. Controlled study using high doses (10 mg / dose) of Δ⁹ – THC administration six times a day for three weeks and its subsequent total withdrawal afterward shows restlessness, anorexia, mild nausea, irritability and sleeplessness in the behavior. Later re-administration in small doses alleviates those symptoms establishing the facts of withdrawal symptoms. Certainly there are many other factors liable for developing tolerance as well as the withdrawal effects.

Effects on central nervous system: It is certain that the major target of cannabis is brain. Therefore, most researches are directed to study its effect on the CNS. Its action on electro-encephalograph (EEG), cerebral blood flow (CBF) and brain morphology are studied over a long period of time in human, primates and animals after exposing them at various stages. According to the study, after six months of smoking marijuana, subcortical alteration of EEG among the primates has been noticed within amygdala, hippocampus and septal region, which are affected profoundly. The studies in human after acute exposure of ∆⁹ – THC indicates enhancement of the alpha power followed by the decrease of alpha frequency and additional decrease in beta activity which is consistent with the findings of experiencing drowsiness. Exposure of 15 – 30 years of chronic marijuana shows large increase of absolute alpha power also higher theta activity in the frontal cortex. Further, acute cannabis exposure to inexperienced users decreases global CBF however for experienced users the effect is just opposite, increase in both hemispheres but primarily in the left temporal and frontal regions. It is speculated that increased anxiety level in the case of inexperienced users may be the cause behind this decreasing effect on CBF. Increased cerebellar blood flow is correlated with the level of intoxication. Further, ∆⁹ – THC enhances the cerebellar metabolic rate in humans and primates. Its role in human brain is localized within specific areas eg, cerebellum and pre-frontal cortex.

Cardiovascular effect: Cannabinoids exert strong cardiovascular effects. The most effective one is ∆⁹ – THC which can induce tachycardia, orthostatic hypotension and prevent platelet aggregation. Noticeable changes in electrocardiogram are observed with variable P and T waves but on the other hand ST segment is somewhat decreased. The exposure to cannabinoids can aggravate angina, congestive heart failure and other preexisting conditions. Sudden high doses enhance the heart rate and reddening of body color. That appearance is due to the vasodilation of peripheral blood vessels. But after prolong exposure bradycardia and subsequent hypotension occurs. The involvement of CB₁ receptor has been identified for hypotensive actions. Identical behavior has been noticed for anandamide also. But anandamide also exerts brief pressor response which is not mediated via the CB₁ receptor. But the hypotensive action occurs via the inhibition of sympathetic tone mediated by the CB₁.

Effect on Multiple sclerosis (MS): It is established that MS is immune-related neurodegenerative disease. It occurs due to the demyelination of neurons that inflicts dreadful pain associated with motor dysfunction as well as loss of coordination along with the severely deficient neuronal functions. The positive effects of cannabis particularly Δ⁹ – THC, cannabidiol (CBD) or even plant extract causes symptomatic improvement within the MS patients. It reduces the pain and associated motor dysfunction. In frequent occasions the drug, Sativex (botanical drug, mixture of CBD and THC) is recommended to treat spasticity among the MS sufferers. As per molecular mechanism, the actions take place by agonist activation of CB₁ and CB₂ receptors exerting anti-inflammatory and neuroprotective effects within the neurons upregulating interleukins in astroglia while reducing cytotoxic factors like nitric oxide, reactive oxygen species and pro-inflammatory cytokines in microglia. Besides the natural agonists, the use of synthetic cannabinoids (WIN 55,212-2 and JWH-015) also exert similar effects reducing pain and motor dysfunction. Presumably, in MS the neuroprotective role of CB₁ and CB₂ receptors are impaired so its enhancement could be the potential treatment approach.

Effect on Alzheimer’s disease (AD): The mechanism behind the action of cannabinoids on AD is not precisely known. Preliminary studies indicate that there is a positive role of both CB₁ and CB₂ receptors. It is highly probable that the production and metabolism of endogenous cannabinoids and its associated signaling become impaired during the disease. But the receptors’ level remain almost the same. So, particularly CB₁ becomes the major focus and the target for this disease. For a limited time, positive results regarding the behavior have been noticed by administering Δ⁹ – THC or any of its analogs. The activation of CB₁ and CB₂ offers neuroprotection against Amyloid-β toxicity which is previously observed in several neurodegenerative diseases. The receptor activation reduces dementia simultaneously enhances the cognitive repair due to anti-inflammatory actions of cannabinoids. Additionally, cannabidiol / CBD prevents phosphorylation of Tau protein which is also another indication of neuroprotection.

Effect on Huntington’s disease (HD): It is also called Huntington’s chorea. It is an inherited neurological disorder created due to the autosomal dominant mutation in either of the parents which causes death of brain cells. HD creates lack of coordination, unsteady or jerky body movement, lowering the motor performances and subsequent production of dementia. Improper utilization of endocannabinoids is noticed according to the animal models. The expression of CB₁ receptor mRNA decreases ~ 27% inside striatum that leads to the loss of motor performances and simultaneously enhances the neuronal aggregation. Identical phenomena are also noticed within the humans suffering from HD. The activation of CB₁ receptor by Δ⁹ – THC plus CBD / Sativex (Novartis) enable to reduce the progression of disease. Other selective CB₁ agonists are also noticed to be effective for neuroprotection. According to the animal and cellular model, activation of Gα_i/o mediated pathways limiting the release of glutamate from cortical neurons could be a part of the reasons. Additionally, CB₁ activation also enhances the expression of BDNF which also provides neural protection. Thus, selective CB₁ agonists can be used in the treatment of HD.

Immune modulation and effect on tumor suppression: Most of the cannabinoids, Δ⁹ – THC, CBD, cannabinol including the endogenous products eg, anandamide, 2- Arachidonyl glycerol and Arachidonyl ethanol amine and synthetic agonists are seen to impose strong immunomodulatory effects. Those induce apoptosis in human lymphocytes / PBMC preventing cellular proliferation by acting as immunosuppressive agents by lowering Bcl-2 leading to the reduction of IL-1. The anti-tumor effect is linked to its induction of apoptosis. Animal experiments showed that intra-tumor injection of Δ⁹ – THC, WIN55, 212-2 and others showed significant recession of gliomas. In cultured C6 gliomas, cannabinoids can induce apoptosis via the CB₂ receptors. Similar effect is observed using specific CB₂ agonist, JWH-133, which is inhibited by the selective antagonist SR144528 (Sanofi). Both endo-cannabinoids and cannabinoids either synthetic or plant derived can inhibit human breast cancer cells. It works via CB₁ receptor while downregulating large form of Prolactin receptor. Cannabinoids are involved in suppressing the tumor growth in multiple ways eg, inducing accumulation of lipid droplet within the cells or by suppressing the angiogenesis. Besides those a large number of human cancer cell lines undergo apoptosis by the action various cannabinoid agonists. Therefore agonist action targeting the receptors using various cannabinoids could be the potential strategy to control numerous proliferating tumors.

Remarks: Cannabis is in use for more than millennia whether for recreational, religious or medicinal reason is not exactly known. In India, religious label is associated with the marijuana use for Hindu religion which is presumably due to the psychoactive effect. For the sake of transitory hallucinogenic effect, the herb has been abused as a trip to pleasure. Medical studies have proven that cannabis imposes psychosis, creates accidents, unwanted sexual encounters and aggressive behavior. The chronic use often induces attention deficit and hyperactivity disorder (ADHD), disorderly conduct and learning disorders. Despite the immense adversarial effects, medicinal values of cannabis are enormous. The plant is a large source of chemical compounds that offer multitudes of beneficial health effects acting as analgesic, neuroprotective, anti-inflammatory, anticonvulsant, appetite stimulator, anti-emetic also protecting from other diseases. The discovery of endo-cannabinoids facilitates the cannabis research further along with identification of its receptors (CB₁ and CB₂) expressing in neuronal and non-neuronal tissues. Following that course, a myriad of drugs has been synthesized particularly for those suffering from the neuronal disorders.

Datura / Dhatura / ধুতরো

General features: The plant belong to Solanaceae family. This particular genus has nine species. Majority of them are poisonous and vespertine / nocturnal by nature, blooming at the evening also spreading pleasant smell. It is popularly known as Devil’s trumpet. The additional names are Moon flowers, Devils’ weed, Jimson weed, Thorn apple or Hell’s bell. The plant was at first discovered and carefully penned by the famous Swedish botanist and physician Carl Linnaeus in 1753 during the course of his expedition. Due to its immense diversity the original home of this plant is never discovered. Although it has been well-mentioned in the Ayurveda (ancient apothecary of India) around millennia BCE. It grows wildly in tropical and temperate zone around the world. The plant also breeds in many North American countries eg, US, Mexico and Southern Canada. Its presence is further observed in the North Africa, Latino countries and Asian nations. In countries like Tunisia, US, Mexico and Canada this herb is severely restricted due to its poisonous behavior. Astonishingly, Datura displays large genetic diversity. Some of the members are seen to be annual whereas a good majority are perennial by the nature. The Indian type titled as Datura Metel is grown as perennial. All varieties share large identity among themselves including the plants like Atropa belladonna, Mandragora officinarum and Hyoscymus Niger since each of them synthesizes hallucinogenic tropane alkaloids within seeds, flowers, roots and leaves in addition to other phyto-components. In warmer climate like in India, the plant, Datura metel grows in the wilderness. It is ~ 3.0 feet high, somewhat furry, having dark violet shoots and oval shaped broad leaves with similar color. The flowers are 6 – 8 inches long venting pleasant smell whose colors varied from creamy white to yellow, reddish or violet. The seeds are encapsulated inside thorny fruits having ~ 4.0 inches diameter. The leaves are 3 – 5 inches long and 3 – 6 inches broad. Despite its powerful hallucinogenic and even poisonous property, it is often used in Ayurvedic medicine for neural problems also acting as aphrodisiac. As per religious concern, the flower and leaves are used ritually for worshipping Lord Shiva also during Ganesh Chaturthi, grand celebration for the Elephant faced Hindu deity, Lord Ganesha (God of success). Each and every part of the plant can cause chemical poisoning owing to large reserve of tropane alkaloids. If ingested it can bring fatality at high doses. Even a small quantity of leaf, fruit, flower or stem can induce severe headache, hallucinations, convulsions and flushed skin. The major psycho-active stimulants are several tropane alkaloids (Scopolamine, Hyoscyamine and Atropine) which impose strong anti-cholinergic effects. Structurally, all of them bear molecular identity especially having quaternary amine. The tropane alkaloids have substituted tropane ring which is a seven membered ring having >N – CH₃ bridging at 1 and 5 position. Atropine and Hyoscyamine (Levorotatory) are stereoisomer whereas Scopolamine holds an oxirane ring bridging the 6 and 7 position. The majority has a side chain propionic group having phenyl group attached to it. These alkaloids act as competitive antagonists toward the muscarinic acetyl choline receptors (mostly M₁ and M₂) which creates delirium, sedation, hallucination and dysphoria. Despite the major poisoning concerns, careful administration of seed or leaves extract can cure numerous ailments eg, inflammation, rheumatism, tumors and bacterial / fungal infections. Additionally, the extracts also show potent insecticidal and herbicidal effects. The recent works have established that several of the isolated components of Datura show great potential as medicines to prevent or cure numerous ailments. Some are already considered as regular medicine to treat deadly illnesses.

Mythological features: The name, Datura originates actually in India from the Sanskrit word (Dhatura or Dhattura) meaning “Thorny apple”. In Bengali it is termed as ‘ধুতরো’ which has been traditionally offered to the Hindu God, Lord Shiva all over India who is the supreme authority holding the power to control peace and destruction. According to the Hindu mythology, Lord Shiva is a hermit and His permanent site is located in the forest of Mount Kailash. Being bare chested nomadic riding on a bull, He wore only a piece of animal skin and likes strange wild flowers. So, during worshipping Him no valuable or exquisite flowers are offered, instead Cannabis leaves, Datura flowers, Bel leaves and Rudraksh (Elaeocarpus ganitrus) seeds are presented as a ritual. As per the Vamana Purana (Hindu mythological text), Datura was sprouted out of the chest of Lord Shiva after guzzling the extreme poison surfaced during churning of the cosmic ocean by Asuras and Devas (other Gods) during great confrontation. Lord Shiva saved the world and creatures by swallowing that deadly nectar. Myth symbolizes the way to lead life by removing rivalry, envy, ego and all menacing elements that would destroy the peace. But to maintain the peace one might need to drink even a poison. In a way, offering Datura flowers to the Great Hermit is a sign of reverence to establish peace in lives since He swallowed the entire world’s sin.

Traditional use: The plant finds uses as a valuable folk medicine. In recent days, it is noted that its careful administration can bring good relief among ample of sufferers experiencing many health problems. As a folk medicine, Datura is frequently used in treating epilepsy, hysteria, insanity, heart problems, fevers, catarrh, diarrhea and few skin diseases. The Chinese and Vietnamese also use it to treat asthma in various ways. The flowers extract can induce general anesthesia quickly within five minutes, if orally consumed that might last for at least 5 – 6 hrs. According to the traditional Chinese medicines, the Datura Metel flowers are used to treat pain, chronic bronchitis and asthma. In Bangladesh, in addition to those, they are also used for convulsions and rheumatism. The dried powder made out of the entire plant are burnt for inhaling to stop abnormal or excessive breathing. The extract is applied around eyes to dilate the pupils. Gargling or sipping of leaf juice can reduce pain and swelling of the gum.

Chemical components and important pharmacological actions: A large variety of chemical compounds from Datura metel are already isolated and characterized regarding their biological roles concerning the therapeutic potentials. The uniqueness lies for its ability to synthesize various tropane alkaloids that has extraordinary role on neural physiology affecting neuro-muscular joints or binding to muscarinic receptors system within the CNS, influencing sensory and cognitive senses. Genetically, herbs belonging to the Solanaceae family synthesize tropane alkaloids which are traditionally enlisted in various ethno-pharmacogical medicines, mostly assigned as pain killers or hallucinogens. The name tropane is provided to the bi-cyclic saturated structure (N- methyl-8-azabicyclo [3:2] octane). Experiments revealed that the precursor for this bicyclic alkyl amine is L – ornithine which converts to ethylene diamine commonly called Putrescine (frequently originates during petrification) by the enzyme, Ornithine decarboxylase (ODC). Putrescine generates from L- arginine. Later on the enzyme, putrescine N-methyl transferase catalyzes to produce cyclized tropane moiety creating Tropinone, which undergoes further changes by the other enzymes producing various tropane alkaloids.

Besides the alkaloids, the plant also produces a large variety of sterols, lactones, and withanolides. All of them also have major potentials in treating inflammation, wound healing, stomach ulcers, microbial infections and preventing / curing many tumors.

Plant parts	%  Alkaloid	Major components
Leaves	0.42	Atropine, Hyoscyamine, Scopolamine, 1-oxo-21,24S-epoxy-(20S,22S- witha-2,5,25,-trienolide, pyrrole derivative(2`-(3,4-dimethyl-2,5-dihydro 1-H- pyrrole-2-yl)-1`-methylene pentanoate.
Seeds	0.42	Hyoscyamine, atropine, other tropane alkaloids, Daturanolone, fastucic acid.
Roots	0.35	Hyoscyamine, Hyoscine, Norhyoscine, Tropine, Cuscohygrine, Apohyoscine, Meteloidine, 3α, 6β-ditigloyloxytropane, 3α-tigloyloxytropane, tigloidine.
Flowers	xxx	Withanolides, Withafastuosin E, Withametelins.
Fruit (pericarp)	xxx	β – Sitosterol, Lanosterol, Stigmasterol, Sitostanol, γ – tocopherol, Triterpene, Daturonolone, Daturodiol.

Pharmacology of tropane alkaloids: From the very early stages of civilization, a few of the botanical species attract keen attention for affecting the sensory and cognitive functions which afterward has been revealed to be owing to its unique alkaloid contents, called tropane. The tropane family also includes cocaine. Although cocaine, despite having the tropane moiety shows no sign of strong interaction with the acetylcholine receptors. But few recent evidences show that cocaine at very high concentration (~ 60 µM) might exert effect on ionotropic nicotinic acetylcholine receptor (nAChR) while blocking the natural acetylcholine interaction. Usually, the action of tropane alkaloids are directed toward the metabotropic muscarinic acetylcholine receptors (subtypes, M₁ – M₅) with high affinities ranging from 100 – 300 pM but much less (> 100 µM) toward the ionotropic nicotinic acetylcholine receptor (nAChR). The muscarinic receptors belong to the superfamily of G-protein coupled receptors (GPCR) existing mostly within CNS tissues. Regarding their signaling character, uniquely, the odd numbered (M₁, M₃, M₅) ones are coupled to G_{q / 11} that activates the phospholipase C initiating phosphatidyl-inositol triphosphate cascade causing the mobilization of intracellular Ca⁺² leading to the activation of protein kinase C. On the other hand the even numbered ones (M₂ and M₄) are coupled with G_{i /0} that inhibits adenylyl cyclase thus lowering the generation of intracellular cAMP that activates G-protein gate K⁺ channels exerting hyperpolarization of plasma membrane of the cells. The interaction of tropane alkaloids are highly stereo-selective indicating the fact that any differences in stereoisomerism would affect the binding affinity to its receptors as well as the pharmacological actions. For example, S – (-) Hyoscyamine binds with lesser affinity than the R – (+) analog. The R – (+) enantiomer exerts anti-nociception and nootropic effects whereas S – (-) produces none. By following the nature of stereo-selectivity, a large varieties of tropane derivatives are synthesized for medicinal needs to produce better analgesic and nootropic agents displaying greater specificity toward any of the acetylcholine receptor subtypes. It is observed that binding pocket inside the muscarinic acetylcholine receptors is acidic by nature which helps interact with the quaternary nitrogen, – N⁺ (CH₃)₃ of either acetylcholine or tropane moiety. The receptors are widely distributed throughout the body and mostly exist in autonomic effector sites, postganglionic parasympathetic fibers, sympathetic and parasympathetic ganglion cells, skeletal muscles, CNS and peripheral nervous system synapses. The physiological role involved in CNS is for the processing of cognition, control of motor actions, sensory functions like pain perception, respiratory and cardiovascular actions and stress responses. Whereas in peripheral nervous system, the receptors are involved in controlling heart rate, contraction of smooth muscle, glandular secretion and vasodilation. Therefore the physiological action of antagonists are obviously versatile thus frequently utilized for numerous therapeutic purposes. It is noted that malfunctioning of muscarinic cholinergic system is often involved in the case of depression, epilepsy, Parkinson’s and Alzheimer’s disorders. So, interests regarding the use tropane alkaloids arise because of their antagonizing role on muscarinic receptor system which leads to its large potential for use as CNS drugs. Additionally, most tropane alkaloids are rapidly absorbed through the gastrointestinal tract. A brief example concerning the physiologic role regarding atropine and scopolamine as nonspecific muscarinic antagonist is cited for better understanding about the tropane alkaloids.

Atropine – A) Inhibits secretion in gastric and respiratory tract, B) inhibits gastrointestinal motor activity for prolong time, C) works on sphincter muscle of iris and ciliary muscle of the lens leading to pupil dilation, D) potent antidote for nerve gas, D) Effective therapy for Parkinson’s disorder at the initial stage, and E) prevent progression of Alzheimer’s disorder.

Scopolamine – Its effect is more pronounced than atropine and follows almost the similar path within CNS causing A) sedation at low doses whereas B) hallucination and disorientation at higher doses, C) prevents motion sickness and D) often used before administration of anesthesia for potentiation.

As a gift of nature besides the tropane alkaloids, Datura synthesizes large stockpile of withanolides (A, B, C, E and others). These are C28 steroidal lactones isolated from the plants belonging to Solanaceae family. They were first isolated from the Indian plant, Ashwagandha botanically named as Withania Somnifera. Withanolides possess unique medicinal properties imparting less toxicity that include, anti-tumor, anti-microbial, radio-sensitization, anti-inflammatory, immune-modulating, adaptogenic, anti-stress, anti-oxidant and anti-feedant effects. The mechanism behind antimicrobial action is primarily owing to its reaction with the – SH groups of various enzymes and metabolites necessary for the survival of microbes. The antitumor action is due to the inhibition of sulfated muco-polysaccharide generation as well as ATPase activity followed by the simultaneous blocking of succinate dehydrogenase actions. The unsaturated lactone of side chain is essential for the antitumor effect particularly 1-keto-2ene and the epoxide moiety. In addition to the withanolides and others, Datura reserves large number of sterols, flavonoids and terpenes which bears enormous medicinal importance including acting as anti-oxidant. Further, the nor-tropanes, Calystegines having numerous isomers (A₁, A₂ —A₆ etc.) have tremendous biological effects also by acting as potent anti-tumor, antidiabetic, antiviral and strong antifeedant. These polyhydroxy alkaloid(s) binds specifically to various glycosidase to the active sites thereby inhibiting the enzymatic actions. In that way, they exert antiviral effect.

Medicinal effects: A large number of different medicinal effects are recorded from the Datura plant which are briefly described.

Anti-tumor and anti-proliferative actions – Withanolides exhibit huge biological effects that include anti-inflammatory, anti-oxidant, anti-tumor, and immunosuppressive also chemoprevention effects. Both in vivo and in vitro, these compounds are capable to inhibit tumor cell proliferation as well as angiogenesis, while inducing Quinone reductase, a phase II enzyme which reduces the electrophile, Quinone thereby helping the important process of detoxification. Basically these chemo-preventive agents lower the risk of developing cancers / tumors or any other inflammatory reactions. The strategies involved are to decrease the phase I enzymes, initially responsible for the generation of reactive species. Whereas simultaneously they induce phase II enzymes which deactivate the intracellularly generated radicals and electrophiles bringing back normalcy to the cells. The anti-proliferative capacity ranges within 1 – 3 µM.

Free radical scavenging and anti-oxidant activity – The most free radical scavenging activity relies on the existence of Tocopherols of which γ – Tocopherol is the major component (~ 80 %). The antioxidant effect is most predominant in aqueous extract of leaf, stem and roots. The plant could be regarded as a natural source of anti-oxidant.

Wound healing effect – The extract of flowers and leaves enhance epithelialization which helps wound healing. The components in extract augment chemotactic effect while attracting inflammatory cells at the wound sites also exerting cellular proliferation due to mitogenic actions of those agents subsequently helping collagen synthesis which is essential for the healing. Several Matrix metallo peptidases and gelatinases are also expressed at the same time to remove fibrin and eschar. Along that process several peptides are generated which exerts angiogenesis and chemotaxis. The progression of wound healing is marked by the presence of gelatinase.

Anti-ulcer effect –   The anti-ulcer activity is verified by experimentally induced ulcer in rat model. The administration of Datura leaves or fruit extract significantly lowers the gastric acid secretion but without any effect on mucin or number of gastric cells. The effect is due to the anti-cholinergic effect of atropine and other tropane alkaloids.

Anti-microbial effect – The compound 5`,7` dimethyl 6` hydroxyl 3` phenyl 3α amine β – yne sitosterol isolated from the Datura leaves has potent antimicrobial effect on large number of microbes. The substance affects the synthesis of peptidoglycan around bacteria that induces osmotic shock causing the death.

Immunomodulatory effect – The compounds which are shown below have been identified to produce strong immunomodulatory effect by activating B and T cells including the secondary antibody production. One of them having the lactone moiety causes selective release of cytokines like IL-2 and TNF – α also.

Effect on memory and cognitive function – It has been observed that blocking of cholinergic neurotransmission affects various brain areas including visual and motor neurons. It also produces impacts memory tasks and subsequently its activation in specific brain areas highly necessary for memory function. Evidently, one of the ingredients Scopolamine is proven to attenuate the memory tasks.

Effect on gout – The alcoholic extract of Datura shows potent xanthine oxidase inhibitory action. It is the reason behind the use of Datura to alleviate the effect of gout. The behavior is identical to Allopurinol, normally use in treating the gout. Both lowers the uric acid deposit in the tissue. Several components are identified which belong to flavonoid and its derivatives possibly works by anti-oxidant mechanism by scavenging the ROS.

Several compounds having different biological properties

Compounds from Datura metel	Plant parts	Physiological action
Withanolides	Flower	Used for Psoriasis.
Withametelins	Flower	Cytotoxic & anti-tumor use.
Datumerine (Alkaloid)	Leaves	Anti-spasmodic.
2-(3-4-dimethyl-2,5-dihydro-1H- Pyrole-2-yl)-1-methylethyl Pentanoate.	Leaves	Antifungal.
Withafastuosin	Flower / Leaves	Used against Psoriasis.
Serotonin	Flower / Leaves / Fruits	Stress and behavioral problem.
Melatonin	Flowers	Works against oxidative stress and  Induces sleep.

Datura poisoning: Unguided use of Datura extracts can cause severe poisoning effect. It consists of dryness in mouth, flushing, thirst, fever, amnesia, urinary retention problem, decreased salivation, pupil dilation, tachycardia, hallucination, palpitations, ataxia, and delirium leading to coma, cardiac and respiratory arrest causing death.

Heliotropium Indicum / হাতিশুঁড়

General features: The name ‘Heliotropium’ originates from the Greek word ‘Helios’ meaning Sun and ‘trope’ for natural tendency to turn its leaves and flowers towards the sun. The plant belongs to Boraginaceae family. Usually, members belonging to this family possess large medicinal properties. But surprisingly they are often counted as weeds. About 250 members of this family are distributed throughout the tropical and subtropical regions around the globe. In India, the major species is Heliotropium Indicum (HI), which normally grows wildly in Tamilnadu, West Bengal, Kerala and several areas of Tripura and Assam. Identical species is also seen in the neighboring Bangladesh, Nepal, many areas of Africa and Latin American nations. In West Bengal and Bangladesh, Heliotropium Indicum (HI) is colloquially known as “Hathi-Shnur” / Hathisundha / হাতিশুঁড় (trunk of an elephant) because of its appearance, having large trunk in the middle. The plant is about ~ 2ft tall and hairy. The leaves are placed alternate. They are ovate or oblong by the look and hairy too. The leaves are 1.5 – 3.5 inches long and 0.5 – 1.0 inches wide. The flowers are small white or occasionally purple. The flowers have five stamens grown on corolla and four lobed ovary. It grows tiny fruits ~ 0.05 inches diameter. The trunk holds the staggered flowers as bunch. The entire plant is used for medicinal needs within many rural communities. The root extract is used as febrifuge or expectorant. The leaf extract is often used to treat ophthalmic problems eg, pink eye, cataract or inflammation of pharynx (tonsillitis) or infections creating erysipelas. The herb has other medicinal role like anti-cancer. All over the India the plant is only used for the medicinal purposes. The different regions of India and other nations use it for diverse health problems (below).

Region	Parts used	Problems
Tamil Nadu Most places	Leaves, Seeds, Roots & flowers	Skin disease, Poison bites, Stomachache, Nervous disorders.
Coimbator district	Leaf juice boiled In coconut oil	Dandruff.
Assam	Root Juice	Ophthalmia
Assam	Leaf Juice	Cuts and wounds.
Assam	Leaf paste	Rheumatism
Nicaragua	Leaf Juice	Skin infection, Whooping cough.
Jamaica	Flower infusion	Menorrhagia

In many parts of Africa, the herb is introduced in treating Malaria, abdominal pain and Dermatitis. But its highest use ever noticed mainly, is for treating Malaria (~ 22 %) throughout the globe. In Thailand the dried flower is administered orally for the sake of permanent sterilization of females. The decoction made from fresh leaves is also used in treating diarrhea, skin rash, menstrual problems and urticaria. In recent days, it is occasionally planted for the decorative reason. Surprisingly, it acts as a trap for controlling flea-beetles that damages the cereal and vegetable plants. On the other hand, it is a quick spreading weed while restricting the production of rice, wheat and maize. Recently, the plant is identified to possess more medicinal properties besides its folk use; a) antibacterial, b) anti-tumor, c) anti-inflammatory, d) anti-nociceptive, e) diuretic and f) anti-fertility. Few pyrrolizidine alkaloids are identified along with the other different components. The pyrrolizidines have anti-tumor role, but they are severely toxic.

It has been identified that those belonging to Boraginaceae family possess large number of pyrrolizidine alkaloids including their N-oxide derivatives. As per the evolutionary measure, they are intended to defend the attacks by insects. Majority having the pyrrolizidine moiety are hepatotoxic especially those containing the N – oxide moiety because of strong chemical reactivity. A large section (~ 3 %) of any flowering plants around this planet produce pyrrolizidine alkaloids for defensive purposes. It is the reason why honey is frequently tainted with this hazardous chemical. So, FDA regulation is imposed to regulate the level in bottled honey. The compounds are cytotoxic because of the ability to form DNA adduct. On the other hand, derivatives like Indicine and a few others are currently under consideration to control tumors like squamush cell carcinoma, non-small cell lung carcinoma and other solid tumors despite having hepatotoxicity. A large number of them are now under consideration for using as chemotherapeutic agent. Recent noticed that Indicine – N-oxide is highly effective against breast carcinoma, especially SKBR3 cell lines (HER positive) when used both in vitro and in vivo mouse model (IC₅₀ ~ 25 µg / ml).

The aerial parts of plant synthesize most of the pyrrolizidine alkaloids. Besides few new alkaloids like Helindicine and Lycopsamine, the roots also contain large quantity of estradiol and other steroids. The seeds also contain chuck full of pyrrolizidine alkaloids eg, Lycopsamine, Cyanoglossifin / Heliosupine, Europine – N-oxide, Heleurine – N-oxide, Heliotridene – N – oxide, Heliotriene and its N-oxide. These are powerful anti-tumor agents and Heliosupine has the most efficiency considering also the cytotoxicity. Besides the alkaloids, leaves also synthesize varieties of long chain amines eg, putrescine, spermidine and spermine. These amines are known to exert versatile influences regarding the cellular metabolism while maintaining the membrane potentials, controlling intracellular pH, Ca⁺² influx or others. Apart from it, the leaves also have huge number of terpenes and steroids eg, β – amyrin, lupeol, β – sitosterol, campesterol, chalinasterol, stigmasterol and few others in low quantity. In general, majority of those sterols exert anti-nociceptive and anti-inflammatory effects by acting as an agonist to the cannabinoid receptors (CB₁ and CB₂) also inhibiting the generation of cytokines and expression of NF – κβ, CREB and cyclo-oxygenase – 2. The herb has large reserve of various essential oils eg, phytol (~ 50 %), 1-dodecanol (~ 7 %), β – linalool (~ 3%) which many plants use for their own survival. Additionally, they have many physiological role for humans.

A significant number of steroids and terpenoids are also isolated showing potent antitumor actions on number of tumor cells when tested both in vivo and in vitro. These two isomers having C11-terpene lactone moiety show promising role on various human colon cancer cell lines (HCT -116 & DLD-1; IC₅₀ ~ 0.3 mM / L). Besides the cytotoxic role, some also show strong anti-oxidant properties.

Medicinal and pharmacological actions: The extracts of HI showed versatile biological actions if tested in vitro or in vivo animal models. The effects are mainly noticed to be anti-microbial, anti-tumor, anti-inflammatory, anti-fertility, anti-tuberculosis, gastro-protective, anti-cataract, analgesic, and wound healing. Some of them are briefly described below.

Anti-microbial effect – The alcoholic extract express strong anti-microbial effect and dose-dependently inhibit the organisms like, Bacillus subtilis (gram positive), Bacillus pumilus (gram positive), Staphylococcus aureus (gram positive), Micrococcus glutamicus (gram positive), Pseudomonas aeruginosa (gram negative), Proteus vulgaris (gram negative, intestinal Hydrogen sulfide producing bacteria), Serratia marcescens (gram negative, wound infection) and Escherichia coli (gram negative). The extract is also effective against many fungi eg, Aspergillus Niger, Aspergillus wentii, Rhizopus oryzae, Saccharomyces cerevisiae and Candida albicans. The pyrrolizidine alkaloids are identified to be the active agents.

Anti-tumor effect – The alcoholic extract of both stem and leaf display strong anti-tumor property; stem – IC₅₀ ~ 60µg / ml) and leaf – IC₅₀ ~ 100µg / ml). The most active agent is Indicine N – oxide. The compound is recently in Phase I clinical trial for treating several deadly tumors despite its high toxicity toxic to liver. The compound blocks the progression of cell cycle during mitosis but exerts lesser effect while organizing the spindle or interphase microtubules. It binds to the tubulin at specific sites subsequently helps depolymerization event of the microtubules. It binds to the DNA causing severe damages which also causes depolymerization.

Anti-tuberculosis effect – The essential oil fraction has anti-tuberculosis property. The identified compounds are Phytol, β – linalool and 1-dodecanol. Each one possesses anti-tuberculosis activity to a certain degree.

Wound healing effect – The alcoholic extract (10 % w /v) showed wound healing effect in animal model on topical application. Around 14^th day, the wounded tissues showed increment of tensile strength followed by the rapid collagenization. Two compounds, Pestalamide B and Glycinamide – N-(1-oxo-octadecyl) glycyl-L-alanyl-L-histidyl have been recently isolated from the stems and leaves show excellent wound healing property by accelerating the events of collagen deposition, angiogenesis and epithelialization leading to the contraction of wound as well as the healing effect.

Anti-inflammatory and analgesic effect – Both aqueous and alcoholic extract show dose-dependent analgesic effect on animal model. But the oral administration (1-2 g / Kg) produces toxicity in kidney, liver, heart and lung. The strong analgesic role is due to the inhibition of synthesis of Cyclooxygenase (COX) to produce Prostaglandins which also exerts anti-inflammatory effect. Further, the compound Rapanone is a potent inhibitor of Phospholipase A₂ which also prevents generation of prostaglandins. The extract is known to help relieving abdominal pain, hypertension and impotency or sexual weakness possibly by its actions on the receptors of smooth muscles. The dose-dependent contractions of various smooth muscles by Acetylcholine and its analogs in addition to nicotine, Histamine and Oxytocin have been noticed. This indicates that various receptors of muscarinic, nicotinic as well as β – adrenergic types are involved in the overall process in addition to strong anti-oxidant properties. In fact, the exact medicinal components are mostly identified for different uses.

Gastroprotective effect – In African countries like the one in Nigeria, the aqueous extract of dried leaves is orally administered to treat fever and ulcer. It has been noticed that the extract protects gastric mucosal layer from ulceration induced by the indomethacin (80 mg / Kg / body weight) as noticed in Wister rats. The anti-histaminic and anti-cholinergic mechanisms are possibly the major role in this event in addition to anti-oxidant effects.

Anti-cataract effect – The alcoholic extract shows anti-cataract activity when tested on multiple animal models. The prevention of cataract formation follows versatile path ways. Usually, the senile cataractogenesis occurs due to progressive decrease of GSH within lenses by various means of oxidative damage. Thus free radical scavenging role of tannins and flavonoids has a distinctive anti-cataract role. Further, the extract balances the right proportion of α – crystalline A & B that prevents the aggregate formation due to the protein cross-linking. Further, extract also maintains water permeability by protecting the protein AQPO, aquaporin that makes the lens permeable to water and other nutrients. In that way the lens can keep maintaining its transparency.

Anti-allergic and anti-conjunctivitis effect – In experimentally induced guinea pigs the extract dosedependently prevents or cures allergic conjunctivitis. It lowers the mononuclear infiltration as well as the inflammatory conditions. The antihistaminic effects are taking place by blocking the respective receptors either obstructing the action of histamine or preventing the release. Additionally, anti-oxidants and steroids present in the extract also play a potent role against this allergic conjunctivitis.

 

 

Hemidesmus indicus / অনন্তমূল

General features: The botanical name is Hemidesmus indicus or sometimes called Indian Sarsapilla. The herb has been in use for more than millennia often mentioned in the ancient Indian Ayurvedic medicine. It is a wild tropical shrub growing on the hedges belonging to the Apocynaceae family of Hemidesmus genus. The shrub is semi erect, occasionally prostrate, but more of a climber by nature. It is also lactiferous and twining. The leaves are flat oblong shaped, growing in opposite direction, short petiole and linear lanceolate. The stem is cylindrical and slender and thick at the nodes. As per frontal appearance, the flowers are yellowish by color with slight touch of reddish purple at the upper edge. But the outside of corolla is greenish color. The root bark or entire root produces pleasing aroma.  The plant is seen to grow all over the India from far north east to the distant west also from north to the extreme south of India, like Kerala or Tamilnadu.  In India, it is often called Anantamul / অনন্তমূল (endless root in Sanskrit). Although considered to be native of India but its existence has been traced back to Egypt, Greece and other Mediterranean places like in Central Asian or Eurasian regions, and largely in the Southeast Asian nations. The most usable part of this shrub is root which has been used for the medicinal needs in frequent occasions but its leaves or stems also finds applications orally and topically. The smashed roots fresh or dried are used for topical applications. Otherwise aqueous or alcoholic extracts are used for the oral administrations. Both roots and leaves have large reserve of phytochemicals. A significant numbers are identified and seen to be medicinally active.

Chemical components:  The most identifiable components are broadly classified as, 1) Terpenoids, 2) Steroids, 3) Polyphenolics and 4) Flavonoids. The major terpenoids are, α & β – Amyrin or its several derivatives, Lupeol and its associated derivatives, Lupanone, Taraxsteryl acetate, Camphor, Borneol, Linalyl acetate, Nerolidol, Iso-caryophyllene, 1,8-Ceneol, α – terpenyl acetate, Hemidesterpene and Ledol. Among the available steroids in this herb, the predominant ones are mostly C21 steroid derivatives of Pregnane moiety glycosylated in different ways eg, Indicine, Indicusin, Hemidescine, Emidine, Medidesmine, Heminine, β – sitosterol, Cholesterol, Campesterol, 16 – dehydropregnenlone etc. The coumarin related compounds are Hemidesminine, Hemidesmine -1 & 2 (in the leaves often used for treating Leukoderma, loss of skin pigmentation). The other phenolic compounds are, 2 – hydroxy-4-methoxy-benzaldehyde, 2 – hydroxy-4-methoxy-benzoic acid, Ferulic acid, Salicylaldehyde, 4-hydroxy-3-methoxy-benzaldehyde, Anisaldehyde, Octanoic acid, Decanoic acid, Do-decanoic acid, Palmitic acid, Thymol, Isobutyl amide, m – Guiaacol, Vanillin, Salicylic acid, (E,Z)- nondienal. Besides those there are few others which remain improperly identified or partially identified. The leaves of this herb possesses considerable amount of flavins like tannins, Rutin or Quercitin or its analogs and derivatives which evidently offers definite beneficial effect on health.

Distribution of phyto-chemical constituents in Hemidesmus indicus

Parts	Chemical components
Roots	Pregnane glycosides – Hemindicusin. Coumarinolignoids – Hemidesmin -1 & 2. Others – α & β – Amyrin and their acetate, Lupeol and its acetate, β – Sitosterol, Hexadecanoic acid, Hexatriacontane, Lupeol octasonate. Oil fractions has glucose, Hemidesmol, Hemidesterol, 2-hydroxy – 4- methoxy benzaldehyde, resin acid and benzaldehyde.
Stem	Glycosides – Indicine and Hemidine. Pregnane glycosides – Hemidescine and Emidine. Pregnane oligoglycosides – Demiculine and Hemidine. Desinine, Indicusin, Hemisine & Demisine. Steroidal compounds – Calogenin-3-O-β-D-digitoxopyranosteroid, desimine steroid, Hemisine steroid. Triterpenoids eg, 3-keto-lup-12-ene- 21->28 olide trieterpene, 12-12-ene-3-β- ol- acetate triterpene.
Leaves	Coumarinolignoids – Hemidesminine, Hemidemin – 1& 2. Flavonoids – Hyperoside and Rutin. Tannin 2.5 %.
Flowers	Flavonoid glycosides – Hyperoside, Isoquercitin & Rutin.

Traditional or folk uses: The decoction made out of entire plant is often used for treating the Asthma, Upper respiratory infection, cough, abdominal swellings or aching limbs as indicated in the ancient Indian Medical literature, Charaka. The syrup prepared from root was listed in the British Pharmacopia in 1864 which has been introduced later in Indian Pharmacopia also. Since then, it has been prescribed for Dyspepsia, Appetite loss, Fever, Skin diseases, Ulceration, Syphilis, Chronic rheumatism, controlling Acne and Leucorrhea. The extract prepared from leaves is traditionally recommended for curing cough, menstrual disorders, dysentery, loss of voices and securing good complexion. The root of this shrub is often mixed with the other herbal extracts and administered for treating many illnesses as directed in ancient Ayurveda. Interestingly, among the several tribes of India, the roots are still frequently being used for the treatment of Gonorrhea, Leukoderma, and bleeding due to Hemorrhoids, Dysentery, and Jaundice even for the prevention of Marasmus (chronic malnourishment of children). Infusion prepared by mixing powdered roots with the milk and sugar is frequently offered to the children as a tonic for curing chronic cough, diarrhea or preventing malabsorption. The root also acts as a good blood purifier and has diuretic, blood thinning and demulcent property in the case of chronic pain. Due to its laxative and febrifuge effect, it clears bowel and lowers the fever. In rural India, the paste prepared from roots and leaves are applied for snake and scorpion bites or regulating any acne problems on face, chest and back. It is also used during pre and post-natal care. The syrup prepared from root possesess pleasant fragrance thus often mixed with the other phytomedicines during their use.

Chemical structures of major phyto-chemicals in Hemidesmus indicus

Medicinal and pharmacological: The herb shows enormous medicinal properties also has been in use since the ancient times. It has large reserve of numerous phytochemicals which evidently exerts versatile physiologic role beneficial for the health. Acceptably, like many others, H indicus does not impose harmful actions. But persons undergoing any specific treatments should be careful of before using any of the concoctions since it may interfere or exert any adversarial effects. Multitude of biochemical researches are already conducted or continuing to identify the exact component(s) which would certainly enrich the modern medicine in all possible ways. Some of the medicinal role of H indicus are described below.

Anti-thrombotic effect – Experiments indicate that alcoholic extract of the root potently inhibits aggregation of platelets. Further, intravenous administration of root extract considerably delays plasma recalcification time also simultaneously enhances the lipoprotein lipase activity; an enzyme that catalyzes the hydrolysis of triglycerides of chylomicrons, VLDL and LDL releasing non-esterified fatty acids and 2- mono-acyl glycerols for later utilization by the tissues. The overall result causes anti-thrombotic effect.

Anti-acne effect – Acne vulgaris is the most common skin disease normally seen for the young adults. It arises due to the bacterial infection caused by Propionibacterium acnes, Staphylococcus acnes or Staphylococcus epidermis developed owing to the obstruction of Pilosebaceous units (hair follicles accompanying Sebaceous glands) of skin on face, back or chest. Studies have confirmed that the root extract of H indicus produces strong inhibitory effect on the bacterium to grow that greatly helps the acne sufferers. Studies conducted on this accord provides the fact that terpenoid fraction mostly generates the anti-acne effect (IC₅₀ ~ 35 – 45 µg / ml).

Hepatoprotective effect – The root extract produces significant hepatoprotective effect in various forms of liver injury as indicated by various animal experiments. The protective effects are possibly due to the Coumarinolignoids like Hemidesmin -1 & 2 providing free radical scavenging activity.

Antioxidant effect – Both in vivo and in vitro experiments confirm its antioxidant role while preventing the lipid peroxidation and simultaneously enhancing the level of antioxidant enzymes which provides protection to kidney and liver from the oxidative stress.

Anticarcinogenic effect – Experiments on animals show potent chemopreventive action on diethyl-nitrosamine induced hepatocarcinogenesis. The exact mechanism is yet to be identified. Additionally, workers indicated that the root extract can protect the microsomal membrane by preventing lipid peroxidation that also protects DNA from the radiation induced breaking of strands.

Anti-hyperlipidemic effect – Experiments on animal have shown that oral administration of root extract for 30 days can lower total cholesterol, Triglycerides, lipoproteins, phospholipids and free fatty acids while increasing the lipoprotein lipase activity in plasma. The experiments further indicated that possibly 2- hydroxy-4 methoxy benzoic acid present in extract could be the major factor responsible in that act.

Anti-venom effect – The most intriguing factor of root or plant extract is to provide anti-venom effect by acting as antidote toward snake bites, Naja kaouthia (Cobra family, neurotoxin like α – bungrotoxin that irreversibly blocks nicotinic acetylcholine receptor at neuromuscular joint) and Daboia russelli (viper family, activates blood clotting factor X generating thrombin which makes fibrin clot). So far, methanolic extract having Lupeol acetate, a pentacyclic triterpene is identified to be one of the most active ingredients working via the inhibition of enzyme acetylcholine esterase thereby enhancing the level of acetylcholine within neuromuscular joint. The enhanced acetylcholine level afterward competes with cobra neurotoxin (α – bungarotoxin) preventing to interact with the nicotinic acetylcholine receptor which is the main target for bringing the lethal and painful effect. In the case of Daboia russelli or snakes belonging to the viper family Lupeol acts slight differently. Lupeol is an enzyme inhibitor of most serine proteases like in the case of acetylcholine esterase therefore it neutralizes all the serine proteases within the venom mixture which is the active component responsible for converting the zymogen, Factor – X to F-Xa, the actual enzyme initiating the blood clotting bringing painful death. The extracts or pastes prepared from H indicus are often used in rural India during these snake bites.

Miscellaneous actions – The anti-ulcerative role on duodenum and gastric system is anticipated to be due to the mucoprotective action caused by the enhanced Prostaglandin generation. The hypoglycemic activity of aqueous extract occurs due to the β-cells stimulation thereby releasing or helping synthesize more insulin. The studies have indicated that alcoholic extract of whole plant or its root dosedependently lowers the neurogenic inflammation and associated pain. The herb also shows immunomodulatory and renoprotective actions against experimentally induced nephrotoxicity.

Eclipta Alba / Eclipta Prostrata / Bhringaraj / ভৃঙ্গরাজ

General features: The plant grows in moist tropical climate, commonly known as False-daisy, Yerba de Togo, Kehraj or Karisalankanni. In India it has been used as Ayurvedic medicine to cure or prevent various ailments for few millennia. The herb belongs to Asteraceae (sunflower) family that grows across the world but majorly noticed in India, Nepal, Southern China, Thailand, Vietnam and several tropical regions of South American countries like Brazil, Peru and others. It is also occasionally found in the many wildernesses of North American nations like US and Mexico. The reddish-purple stem of the plant is about 36 inches tall and appears cylindrical having grayish roots producing white flowerheads, 0.25 – 0.32inch diameter whose achenes are compressed and headed. The leaves are ovate or egg-shaped. In most places of the India it is ordinarily named as Bhringaraj (ভৃঙ্গরাজ). It is also botanically called Wedelia Calendulacea which often grows two kinds displaying white and yellow colored flowers. Both have almost the similar ingredients producing identical health impacts. The plant has been traditionally used as Ayurvedic medicine also recognized as being popular for its number of medicinal role either to cure or prevent various common ailments like liver problems, diabetes, hair growth, eye health etc. The extract of Eclipta Alba is known for a long time to be effective in hair-growth (topical application of Pet-ether extract – 5%) and experimentally claimed as being comparable to 2 % solution of Minoxidil (anti-hypertensive medication often used to cure hair loss particularly for the androgenic alopecia). For oral intake, either ethanolic extract or else the fresh plants is used as vegetable. It has pain reduction abilities outperforming Aspirin. It even receives attention for blood pressure lowering ability, anger management, diuretic action and immune boosting effects. Its further use is now seen in varieties of cosmetics and beauty products claiming to have a promising role on skin tone. It is a good mosquito repellant also displaying anti-venom and anti-viral properties. In many parts of India especially in North and South regions, the leaves of E. Alba are often consumed as vegetable eating with lentil soup along with the other vegetables and rice.

Bhringaraj oil for hair growth and regeneration: From the very ancient time the extract from its leaves is used either to regenerate or grow or even removal of gray coloration from the hair. In recent days, number of animal experiments have established the effects and some of the components are also identified, although not exactly. The components stimulate blood circulation of the scalp and help secreting few factors enabling to rejuvenate the hair follicles for hair growth. Many people prepare this herbal oil at home using fresh leaves of E. Alba. In most occasion refined coconut or olive oil is used for the extraction while heating with chopped or paste prepared from the leaves. After filtering the concoction through nylon mesh, the oil extract is stored in a bottle. Before its use, the oil is slightly warmed up and massaged on the scalp for quick absorption. The effect can be observed in ~ 2 month period.

Phytochemicals produced in different parts of the plant:

Leaves – Coumestan derivatives like Wedelolactone, Des-methyl-Wedelolactone, Stigmasterol, α – terthienyl methanol, Des-methyl-Wedelolactone – 7-glucoside, Alkaloids, Apigenin, Luteolin, Wedelic acid, 25 – β – hydroxy-Verazine, Ecliptine and Nicotine.

Roots – thiophene, eg, 5I-senecioyl-oxymethylene-2-(4-isovaleryl-oxybut-3-ynyl)-dithiphene and several of its identical derivatives, 1-Hetriacontanol (straight chain alcohol C₃₁ H₆₃ OH), Stigmasterol, Ecliptal and 14-heptacosanol.

Stems – Wedelolactone, Wedelic acid, L-terthienyl methanol, Apigenin and Luteolin.

Seeds – large reserve of various sterols. Wedelic acid and Echinocystic acid are triterpene. They can be found also in glycoside forms.

Aerial parts – β – amyrin, Luteolin, Luteolin – 7 – O glucoside, Apigenin, Wedelolactone, Thiophene derivatives and Eclaba saponins.

Whole plant – Ecliptine, Sugars, Resin, Nicotine, Stigmasterol, Tri-terpene saponins, Eclalbatin, Ursolic acid and Oleanolic acid.

Major chemical components and its properties: It has been noticed that the herb produces a great many number of bioactive compounds which comprises Wedelolactone, Des-methyl-Wedelolactone, triterpenes, flavonoids, steroids, polypeptides, poly-acetylenes and thiophene derivatives. The extract offers numerous pharmacological properties eg, antimicrobial, analgesic, anti-nociceptive, anti-inflammatory, antiviral, hepatoprotective, immunomodulatory, anticancer and others. Additionally a large section of terpenoids along with their respective glycosylated derivatives are isolated as well as characterized for bioactivities. Few physiologically active alkaloids are identified also in this herb. The root extract contains poly-acetylene and thiophene compounds. In several occasions, the extract also shows the presence of Nicotine and Nicotinic acid along with Verazine, Ecliptabine and few other alkaloids. Besides those components, there are number of Coumestan analogs like Wedelolactone, Des-methyl – Wedelolactone but not the Wedelic acid which is a triterpene also available in the plant. The Coumestans are generated by the enzymatic oxidation of Pterocarpan which is also produced via the oxidation of isoflavone. Coumestans are very similar to the bioactive compound, Coumarin (normally used in treating lymph-edema also enhances plasma Anti-thrombin III preventing arterial blood clotting). Coumestrol binds to the ER- β – estrogen receptor mimicking 17 β – estradiol with lesser affinity than 17 α – estradiol. In that way it acts as a phyto-estrogen.

The Coumestans and its analogs like Wedelolactone or Des-methyl-Wedelolactone are best extracted (~ 16 %) by the ethylacetate whereas alcoholic extraction provides much less (~ 4 %). Wedelolactone analogues are probably the most bioactive products.

The role of Wedelolactone and its analogues like Coumestans are enormous. Below is some of their effects and way of actions.

Anti-inflammatory effect – It suppresses production of IL-6, TNF – α and subsequent PGE₂ generation. In addition, anti-inflammatory, anti-allergic and anti-asthmatic manifestations of Wedelolactone and Gallic acid occur via the interaction with G-protein coupled receptor – 35 (orphan receptor) while behaving as agonists. The effect is somewhat identical to Cromolyn (di-sodium – chromoglycate), a potent anti-asthmatic, anti-inflammatory and anti-allergic drug.

Beneficial effect on osteoporosis – The compound enhances osteoblastogenesis via ER, JNK mediated BMP-2 and smad1/5/8 phosphorylation.

Anti-cancer role – It can inhibit estrogen receptor mediated breast, endometrial and ovarian cell growth. It also downregulates c-Myc oncogene in most of the prostate cancer cells. It also prevents abnormal proliferation by regulating key members of NF – κβ signaling pathway.

Miscellaneous effects – The compound inhibits Na⁺/K⁺ – ATPase in kidney tubule thus producing significant effect on the arterial blood pressure. Further it also interacts with the Benzodiazepine receptor in CNS thereby acting as an anxiolytic drug producing calming effect along with induction of sleep in brain. Ecliptal / Des-methyl-Wedelolactone besides acting as Na⁺/K⁺ – ATPase inhibitor also inhibits other enzymes like DNA helicase-1 (used during DNA, RNA strand separation) and Tyrosine – DNA-phosphodiesterase polymerase kappa (inhibiting NF – κβ generation). Both of the compound can inhibit trypsin. It is the underlying reason behind appetite reducing effect of this herb.

Analgesic effect – The effect has been confirmed by animal experiments using all the models. The alkaloid fraction of ethanolic extract has been identified to be the most efficient in this aspect.

Anti-inflammatory effect – The oral administration of alcoholic extract showed dose-dependent anti-inflammatory action in the experiments using various animal models. The effect is possibly due to Wedelolactone and other related derivatives inhibiting the action of 5- lipoxygenase.

Anti-aggressive behavior – The anti-aggressive and calming behavior has proven by the animal experiments using aqueous extract of E. Alba. The effect is dose-dependent, 100 – 200 mg / Kg. No exact chemical components have been identified but preliminary works indicate that Apigenin and several others could be responsible behind that act.

Anti-bacterial, Anti-fungal & Anti-malarial actions – The effective component(s) is Wedelolactone and its other derivatives. The extract is tested against bacterial species like Staphylococcus epidermis, Salmonella typhimurium and several others. It shows good potency at 25 µg / ml. The extract or Wedelolactone fractions are superbly active against many fungi eg, Candida albicans, Candida tropicalis and Rhodotorula glutinis. The effects are much comparable to the standard antibiotics used against respective fungi. The anti-malarial actions are tested in animal model using ANKA strain mice infected with Plasmodium berghei. The leaf extract shows schizontocidal effect (destruction of sporozoan parasite) to suppress the infection.

Anti-hyperglycemic effect – If taken orally (leaf suspension 2 – 4 gm / Kg body weight) for about two months then it would significantly lower the blood glucose level (from 372 ± 33 to 117 ± 23) including the reduction of HbA1C. A subsequent decrease of glucose – 6 – phosphatase and fructose 1, 6 bisphosphatase along with the increase of activity of liver hexokinase has been observed.

Hepato-protective effect – Using animal experiments it has been proved that E Alba extract provides potent hepatoprotective action against CCl₄ injury or Tylenol induced toxicity of the liver. One of the identifiable components is Oleanolic acid.

Hypolipidemic effect – The alcoholic extract causes significant reduction when assessed by the lipid profile of serum and liver. The triglyceride, total cholesterol as well as low density lipoprotein cholesterol levels are also reduced to the considerable extent. A number of components are responsible for the effect.

Neuropharmacological effect – Experiments on animals convinced that consumption of aqueous or alcoholic extract enhances learning and cognitive behavior. The daily use of this herb shows strong nootropic effect, particularly for the human. Combination of several identifiable factors are responsible for the effect.

Water clover / Marsilea quadrifolia / শুষনি শাক্

General features: The plant belongs to Marsileaceae family. In English, it is known as ‘water clover’ whereas in Bengali it is named as ‘Sushni shak’ (শুষনি শাক্). It is herbaceous that grows in warm or tropical areas of the world like, India, China, Vietnam, Japan, central and Southern Europe, Caucasian regions, Afghanistan and a few regions of the United States. The deciduous green aquatic fern holds four parted shamrock-like leaf, often called ‘Four parted clover’. The plant grows in sandy or medium soil (pH – 6.5 to 8.5) under wet condition, irrespective of shade or no shades. It grows well in submerged water with fronds floating on the surface. If kept inside an aquarium for ornamental reason, it expresses growth under fully immersed condition on foreground by spreading the runners. Normally in shallow aquatic condition, leaves float on the surface whereas on land it can stand over the ground. The leaflets are ¾ inch long ellipsoid like shape. The petioles are ~ 8 inches tall. For normal growth Marsilea does not require any rich or special substrate. It has the ability to grow everywhere, often categorized as invasive species although not officially listed. By nature, the plant germinates from sporocarps. Therefore, in order to germinate, the surface of sporocarps needs to be fractured allowing water entering inside to initiate germination. Interestingly, the event is infrared light dependent therefore full sunlight is very appropriate for its growth. The generated sporocarps which after being abraded when immersed in the water undergoes bursting on swelling, releasing spores for the germination. The gametophyte formation occurs in single day whereas the roots and shoots take about two to three days to show up. The entire time-period taken to grow up being a matured plant takes about three months. In many parts of the world the matured plant is considered to be a food, known almost for ~ 3000 years, especially in the event of famine or dire scarcity of food. It is enriched with starch and protein. Uniquely, it can also survive extreme low temperature, about – 15^◦C but the growth will be retarded. This fern is known in West Bengal and Bangladesh as ‘Shusni’. It is also popular in Jharkhand and some parts of Bihar as for cheap nourishing food. Colloquially, in Bengali, the term ‘Shusni’ means ‘don’t sleep’ possibly, for its sleep-inducing effect. Traditionally, tribal and poor locals eat it as cooked vegetable. It satisfies their hunger and offers relaxation through sleep after the day’s hard labor. It is called poor mans’ vegetable and by the grace of nature abundant in the villages around tropics.

Use as folk medicine: Besides being used as food, the plant or its extract finds good deal of application as a folk medicine acting as anti-inflammatory, depurative, febrifuge and diuretic. In Indian villages, it is also used to treat snakebite, abscess, cough, bronchitis and as a vegetable that can induce sleep while relaxing the body and mind. In China, it is used to treat fever, hepatitis and alcoholism. In Japan this is used for the sake of skin care preparation. Its medicinal use is further noticed in preventing epileptic seizure. As a folk medicine it is known to be a memory enhancer also enabling to help the learning behavior. Some even claim about its anti-diabetic role. Most of the traditional applications are authenticated in recent days through the in vivo and in vitro experiments.

Chemical components and pharmacological effects: Analysis of Marsilea quadrifolia indicates that the dried material has high protein content but low in mineral and β – carotene. It is an edible aquatic plant, intensely cheap but highly nutritious which makes it an ideal food for the densely populated regions of this planet with less agricultural land also for the poor. The level of phyto-ingredients shows seasonal variations. The average contents in entire plant (mg / g) are: carbohydrate → 200 ± 0.2, protein → 51 ± 3.4, free amino acids → 28 ± 3.2, flavonoids → 3 ± 0.4 and saponins → 2.8 ± 0.5. The identified major phyto-compounds in leaves and stems are phenolics, flavonoids, alkaloids, tannins and saponins. The contents (mg / g dry powder) are slight higher in leaf than the stem eg, phenolics → leaf 8.34 ± 0.92 whereas stem 7.31 ± 0.46, flavonoids → leaf 7.46 ± 0.64 but stem 6.45 ± 0.68, alkaloids → leaf 6.12 ± 0.51 and stem 5.89 ± 0.61, tannins → leaf 6.58 ± 072 and 6.07 ± 0.56, but contrarily, the saponins in leaf (5.32 ± 0.48) is somewhat less than the stem (6.30 ± o.58). It is certain that tannins belong to the family of polyphenolics whereas saponins are glycosylated cyclic triterpenes, amphipathic by the nature. Among the polyphenols of Marsilea, about eighteen have been isolated and identified. Many are seen to be the derivatives of kaempferol displaying anti-oxidant properties when assayed by following in vitro free radical scavenging study using DPPH or in vivo experiments using stress induced physical restraint on mice and measuring the liver SOD (Super oxide dismutase), plasma MDA (malondialdehyde), ALT (Alanine amino transferase) and AST (Aspartate amino transferase). The presence of other flavonoids are also noticed. Quercitin is one of them which exerts the most anti-oxidant effect. The experiments further indicate that aqueous extract of Marsilea has strong hepatoprotective effect. Below is a table for few physiologically beneficial compounds belonging to various categories of Marsilea quadrifolia.

Besides the polyphenolics, flavonoids or steroids, few more bioactive compounds have been isolated recently from the plant extract eg, Marsiline (ester of 1- tricontanol and hexacosanoic acid) that exerts sedative and anti-convulsant effects. The other one is Marsilagenin, a pentacyclic triterpene that offers anti-depressant influence by interacting with 5-HT2A (Serotonin) and Benzodiazepine receptor. Considering multifaceted effects, the extract shows good anti-tussive or expectorant activity when administered to the NH₃ liquor and SO₂ induced coughing. It is known from the early days that the plant has been long used as a cough suppressant although no exact component is hitherto identified. As indicated from its folk medicinal use, the plant extract helps insomnia and other mental disorders like in the case of learning problems or memory loss for the induced (scopolamine or electroconvulsive shock) amnesic animals. The effect of convulsion removes away within 2days in the case of extract treated animals. The experiments provide further fact that extract can inhibit acetylcholine esterase significantly within cortex and hippocampus thereby raising the level of Acetylcholine level which subsequently benefits the learning problem sufferers and memory disordered persons. The treatment also upregulates the muscarinic receptor level within frontal cortex. The preliminary identification indicates the effective compound is Marsiline.

The alcoholic extract also acts as inhibitor of 5 – α – reductase, an enzyme responsible for the conversion of testosterone to dihydrotestosterone (DHT) helping enlarge the prostate. Inhibiting the enzyme would reduce the risk of formation of benign hyperplasia or even prostate cancer. Marsiline or its close analog could be responsible behind this beneficial role of Marsilea.

It has been documented that di-terpene alcohols have antitumor / anticarcinogenic role. They are usually derived from the plant chlorophyll and acting as the precursor to Vitamin K and E synthesis. Its anti-inflammatory, anti-oxidant and immunostimulatory effects have been tabulated also. Among those Phytol takes the precedence. It is acyclic monosaturated diterpene that offers pleasant aroma thus often used in many cosmetics also. Like many of its plant analogs it also provides antimicrobial activity against Myobacterium tuberculosis and Staphylococcus aureus. Phytol also has strong anticancer role on number of cancer cells both in vivo and in vitro by exerting apoptosis through the activation of Caspase – 9/3.

Marsiline (ester of 1- tricontanol and hexacosanoic acid, C₅₆H₁₁₂O₂).

Medicinal role: Until now the plant has been demonstratively used for the following remedial purposes.

1. Anti-inflammatory.
2. Diuretic
3. Febrifuge

For the external uses:

1. Snake bites.
2. Skin injuries.

Medicinal and physiological effects of compounds from Marsilea quadrifolia

Name of the compound	Nature of the compound	Physiological effect
3,7,11,15 – Tetra methyl-2- Hexadecane-1 –ol.	Terpene alcohol	Anti-microbial, Anti-inflammatory.
Ethyl ester of hexadecanoic acid	Ethyl palmitate	Pesticide, anti-androgenic, Nematocidal, 5-α – reductase inhibitor.
Phytol	Diterpene	Anti-microbial, Antitumor, Antioxidant, Diuretic.
9,12 – octadecan-dienoic Acid / ester	Linoleic acid / ester	Hypocholesteremic, Nematocidal, Anti-arthritic, Hepato-protective, Anti-histaminic, Anti-cancer, Anti-eczema, Anti-coronary, Insectifuge.
5a-androstan-16-one, cyclic Ethylene mercaptide	Steroid	Anti-microbial, Anti-cancer, Anti-inflammatory, Anti-arthritic, Antagonist to prostatic androgen Receptor.
2-piperidinone, N- [4-bromo-n- Butyl]	Alkaloid	Antimicrobial, Anti-inflammatory.
Spiro [androst – 5-ene-17,1`- Cyclobutan]-2`-one, 3-hydroxy -, (3a’, 17a’)-	Steroid	Anti-microbial, Anti-cancer, Anti-inflammatory, Anti-arthritic, Anti-asthmatic, Hepato-protective.

But it has also more potential for controlling other serious illnesses like hypertension, neurological diseases (memory loss, problem of learning behavior), tumor formation and several bacterial infections (Myo-bacterium tuberculosis, Staphylococcus aureus). Further searches are needed for exact identifications of compound(s) responsible for any specific ailments.

Adverse effect: The plant contains thiaminase, which reduces the level of Thiamin by degrading it causing the deficiency of Vitamin B1 leading to Beriberi. But cooking would destroy the enzyme.

Bryophyllum pinnatum / Kalanchoe pinnata / Patharchatta /পাথরকুচি পাতা

General features: The scientific name is Kalanchoe pinnata whereas its botanical designation is Bryophyllum pinnatum (BP). Kalanchoe / Bryophyllum (BP) is recognized as a medicinal plant having numerous physiologic role. As per folk medicine, its beneficial effect is largely confined to treat infections, inflammation or rheumatism in many of the rural areas. Contrarily, in Trinidad, it is often used for treating hypertension. The recent studies reveal more of its physiologic actions. Reports show that BP also has the immunosuppressive effect. By nature, it is a succulent perennial tropical house-plant, popularly named in the western world as ‘Goethe plant’ because the celebrated multitalented German poet (Johann Wolfgang Goethe) also being a naturalist loved it fervently. He often used to give away the plantlets to his friends, as a gift while visiting their home. The legendary poet also discussed about the plant in his writing “Geschichte meiner botanischen” (History of my botanical studies). In Bengali, BP is known as Patharkuchi Pata (পাথরকুচি পাতা). In the state of Orrissa, it is named as Omorapoi, meaning, ‘Deathless plant’ whereas in Maharashtra, the plant acquires the name “Panfuti” meaning, growing out from the leaves. BP has a unique feature for its teeming growth from the borders of phylloclades (photosynthetic roots) of leaves. Each leaf grows about 6 – 10 plantlets. The plant belongs to the Crassulaceae family which are succulent by nature, frequently popular for the horticultural or ornamental reason. It has been identified to be the native of Madagascar although afterward naturalized in many tropical and subtropical regions of the world, like in Asia, West Indies, Macaronesia, Polynesia, Melanesia, Australia, Galapagos Islands and Hawaii. In Hawaii, it is listed as an invasive species. Normally, the plant is ~ 3ft tall although some of the species are much taller like, ~ 8 ft. The oval shaped leaves vary in sizes, 2 – 3 inches in length. The leaves produce crenatures. At the extremities of the lateral nerves, new budding comes out having roots, stems and leaves. Eventually the new plantlets drop off becoming self-growing new plants. The flowers are reddish purple pendent, spreading panicles. The calyces are red or green at the bases where as the corolla are purple reddish and constricted at the middle.

History of BP / Kalanchoe: It has been speculated that distribution of BP throughout the tropics occur mostly due to its versatile medicinal role by the navigators around 1^st century AD.  Presumably, they were Malayo-Polynesian natives from Indo-Malay archipelago later settled in Madagascar. From there, BP was eventually introduced to other islands and lands connected via the Indian Ocean. Its move to Caribbean and South America possibly took place during the slave trade by the European traders from West Africa. Its further move to Australia or Papua New Guinea might happen much later which is estimated to be around the last century. But which ways it might move, the main objective was medicinal which afterward was changed to house-plant for its graceful look.

Folk medicine use: It is one of the largest used ethno-medicinally consumed plants of Asia, Africa and islands of Indian Ocean, Caribbean in South Atlantic and Fiji, Hawaii etc of the South Pacific. In African nations, it is used to facilitate the child birth. In India, it is used to provide relief from abdominal discomfort, flatulence, indigestion, boils, bruises, cuts, diarrhea, dysentery, diabetes, headache, kidney stone, scabies, carbuncle and urinary insufficiency. Its further use is also directed to treat rheumatism, ulcers and wound healing. Below is the various facts about its action as folk medicine:

1. Anti-tumor; B) Prevention of gall stone and kidney stone formation; C) Anti-microbial; D) Anti-proliferative; E) Antiviral; F) Anti-protozoal; G) Antileishmanial; H) Anthelmintic; I) Insecticidal; J) Anti-allergic; K) Analgesic; L) Anti-nociceptive; M) Anti-inflammatory; N) Muscle relaxant; O) Anti-pyretic; P) Anti-convulsant; Q) Anti-depressant; R) Sedative; Anti-diabetic; S) Hepatoprotective; T) Thrombolytic; U) Anti-histaminic; V) Anti-hypertensive; W) Immunosuppressant.

Chemical components and pharmacological actions: The plant contains flavonoids, alkaloids, sterols, tannins, phenolic components along with the elements like Calcium, Magnesium, Potassium, Phosphorous and Sodium in macro level whereas Iron, Zinc and vitamins eg, ascorbic acid (vitamin C), niacin (member of Vitamin B₃ complex), thiamin (Vitamin B₁) and riboflavin (Vitamin B₂) in micro level. Below is the list of several important chemical components produced in BP.

Major chemical components

Compound category	Name
Phenolics	Syringic acid, Caffeic acid, 4-hydroxy-3-methoxy cinnamic acid, 4-hydroxy benzoic acid, p-hydroxy cinnamic acid, p-coumaric acid, Ferulic acid, Protocatechuic acid, Phospho-enol pyruvic acid.
Flavonoids and its glycosides	Astragalin, 3-8 dimethoxy-4-5-7-trihydroxy flavone, Epigallo- Catechin-3-O syringate, Luteolin, Rutin, Kaempferol, Quercitin, Quercitin – 3- O-di-arabinoside, Quercitin – 3 -L-Rhamnoside, L- Arabino-furanoside, Kaempferol – 3 – glycoside, Kaempherol – 3  -O-α-L – arabinopyranosyl (1→2)-α-L-rhamno- pyranoside, Quercitin-3-O-α-L-arabinopyranosyl (1→2) α-L-rhamno-pyranoside, 4`,5`-dihydroxy-3`,8`-dimethoxy flavone-7-O-β-D- gluco-pyranoside  (Those have potent anti-leishmanial effect).
Terpenes and sterols from fresh Leaves and aerial parts of the Plant.	β – Amyrin, Taxasterol, Bryophyllol, Bryophollone and  Bryophollenone, Oleanane, Bufadienolides (Bryophyllin A & C),  β – sitosterol, Campesterol, stigmasterol other sterols.
Enzymes (leaves)	Phosphophenol-pyruvate carboxy kinase Phosphophenol-pyruvate Carboxylase, Pyruvate orthophosphate di-kinase, Ribulose-  1, 5-biphosphate carboxylase / oxygenase etc. In addition it has DNA Topo-isomerase, Glycolate oxidase, Carbonic anhydrase which have potent role in metabolism.

Bryophyllin A & C have the insecticidal property. Including Bryophyllin A and C, there are five Bufadienolides isolated from this plant displaying potent antitumor actions. The Bufadienolides are compounds possessing steroid like moiety. They also exist in glycoside forms and often act as cardiac glycosides exerting potent cardiac action enable to induce cardiac arrest also causing bradycardia (slow heartbeat) and tachycardia (rapid heartbeat). The term, Bufadienolides came from the toad family, Bufo frog and –adien- indicates having two double bonds inside the lactone ring whereas –olide- signifies lactone structure. All of them are physiologically active also important for the medicinal use.

Besides Bufadienolides, BP synthesizes huge number of various polyphenols and flavonoids. Rutin, Kaempferol and Epigallocatechin are produced in considerable quantities. Rutin is a flavonoid glycoside, normally found in various foods. It lowers deep vein thrombosis, endothelial dysfunction and venous insufficiency. Kaempferol has tremendous beneficial role on health preventing and curing number of deadly diseases like various cancers, Breast, prostate, ovary, uterine, bladder, colorectal, bladder and leukemia. It induces apoptosis in malignant cancer cells, prevents angiogenesis and proliferation of cancer / tumor cells, inhibits aromatase and VEGF production etc.

The plant also has large reserve of various sterols like stigmasterol, β – sitosterol, Campesterol etc. The phytosterols are welknown for beneficial role on health. For example, Stigmasterol which acts as precursor for the bio-synthesis of progesterone, estrogen, androgens, corticoids and Vitamin D₃. It also has the ability to ovarian, prostate, breast and colon cancers. It is also the precursor to Boldenone, anabolic steroid often used / abused in veterinary and sports medicine. Additionally, it has several other physiologic role eg, analgesic, anxiolytic, anti-allergic, neuro- and Cardioprotective. Epigallocatechin like Kaempferol, it also exists in food and has strong antioxidant role that exerts immense beneficial effects on health like immune boosting, prevention of lipid peroxidation lowering cardiovascular and other metabolic diseases.

Medicinal effects: The versatile effects of BP have been recorded while noticing the use as folk medicine. A great majority of which have been authenticated through the scientific works.

Anticancer and anti-tumor effect – The active material behind anticancer / antitumor effect of BP extract is due to Bufadienolides which can inhibit proliferation and lowers the cell viability. The compounds interrupt integrity of centrosome and chromosome alignment at metaphase. These phenomena target exactly the mitotic events leading to cell death. Among the compounds, Bryophyllin A plays the highest role.

Anti-diabetic effect – The alcohol water extract of BP lowers the level of blood glucose, Low density lipoprotein (LDL) and Triglyceride in Streptozotocin induced diabetic rats.

Anti-nociceptive and anti-inflammatory effect – The aqueous leaf extract of BP dose-dependently (25 – 800 mg / Kg intraperitoneal injection) produces significant anti-nociceptive and anti-inflammatory effects against thermally (hot plate) and chemically (acetic acid) induced stimuli models within mice when compared with Diclofenac (non-steroidal over the counter drug). The active ingredients are supposedly flavonoids and tri-terpenoids fractions.

Anti-convulsant effect – The leaf extract applied during different animal experiments following various tests like head-dip and evasion, muscle tone (chinney tests, inclined screen tests, climbing testes), anticonvulsant tests (using strychnine and Picrotoxin induced convulsant) show effectiveness in reducing the symptoms of convulsion. The most efficiency is observed at dose of 200 mg / Kg without showing any toxicity.

Bactericidal, antifungal, antimicrobial and anti-protozoal activity – The aqueous extract of BP shows antibiotic effect against Staphylococcus aureus, Bacillus subtilis, E coli, Pseudomonas aerugnosa. Its bactericidal action is also noticed toward Streptococcus pyrogenes, Streptococcus faecalis, Proteus spp, Shigella spp, Salmonella spp and Serratia marcesecens. The extract is seen also being effective toward protozoal diseases like Leishmaniosis which is possibly due to tannins. The alcoholic extract can act against filamentous fungi like Alternaria alternate and Rhizoctonia bataticola and yeast Candida albicans.

Anti-ulcer effect – The alcoholic extract of BP shows potent Gastroprotective and anti-ulcerative activity in experimental animals. It protects mucosal layer while inhibiting its damage or erosion. Several compounds have been identified but Bryophyllin C is found to be most effective one.

Hepatoprotective effect – The administration of both aqueous and alcoholic fractions of leaves shows strong hepatoprotective action in chloroform induced toxicity of experimental animal model. The result shows significant reduction of serum bilirubin, SGPT and other markers by the plant extract.

Diuretic and anti-urolithic action – The aqueous extract shows significant diuretic and anti-urolithic activity by oral dose-dependent oral administration (100 – 800 mg / Kg) to male wistar rats while measuring the urine volume output and electrolyte level while keeping the animals in metabolic cages.

Anti-oxidant effect – The leaf extract of BP shows strong anti-oxidant property. In that context, alcoholic extract displays more efficiency than the aqueous counterpart. The extent of phenolic and flavonoid components are seen higher in the alcoholic extracts. Those have heavy metal chelating ability. The chelating event reduces metal induced generation of free radicals. Besides chelating, the presence of Rutin, Kaempferol and other phenolics and flavonoids are responsible for the overall anti-oxidant role also by scavenging the generated free radicals which is well known to be beneficial for preventing any cardio-vascular diseases.

Miscellaneous actions – The other medicinal properties of BP are:

Prevents bleeding, Analgesic – relieving pain, Anti-aggregant – prevents platelet aggregation and thrombus formation, prevents dysentery, Antiseptic – prevents infection inhibiting the growth of infection, Anti-spasmodic – Relieving involuntary muscle spasm, immunomodulatory – modifies functioning of the immune system, emollient – softening effect on skin.

 

Rosemary / Rosmarinus officinalis

General features: It is a perennial evergreen herb with needle shaped leaves emitting woody fragrant, officially named Rosmarinus Officinalis. The plant belongs to Lamiaceae family (taxonomic family of mint although bears no characteristic flavor) displaying bluish white flowers. It is a native of Mediterranean regions. The plant grows in neutral to alkaline (pH 7.0 – 7.8) soil. It is often propagated from the existing plant. The name ‘Rosemary’ means “Dew of the Sea” in Latin. In Latin “Dew” is ‘Ros’ and “Sea” is ‘marinus’. The name is created because of its Mediterranean origin. The herb provides warmer and astringent taste making tasty soups, sauces, stews, roasts or stuffing, frequently seen in Italian cuisine. The leaves are used for culinary uses. Usually, fresh, dried or powdered leaves is used for most culinary purposes. Teas or liquid extracts are also often consumed by many. The herb has few health benefits like improving memory, concentration, digestion and alleviating the aging of brain. It is a good source of Iron, Calcium and Vitamin B-6. For medicinal facts, it has been acclaimed from the very ancient times. Besides traditional medical use to ease the muscle pain, Rosemary boosts memory, immune system, promotes hair growth and improves blood circulation. Its essential oil is used for preparing the cosmetics. If ingested at high doses it may cause vomiting, pulmonary edema or even induces coma. The herb is displayed as decorative plant in garden where it is also acting for controlling pests. Its extracts and essential oils are applied for culinary, cosmetics and medicinal purposes. It is normally used for stuffing the meats.

History and mythology: According to the biblical story, Virgin Mary while resting unfurled her blue cloak on the white Rosemary bush. From then on, the flowers acquired bluish appearance and in turn received the name, Rosemary. The flower is considered sacred to the Greeks, Romans and Egyptians. Both flowers and shrub were loved by the ancient scholars and poets, even by William Shakespeare signifying as a sign of beauty and remembrance. The famous 15^th century English scholar, Sir Thomas More once composed a poem – “As for Rosmarine, I lett it runne all over my garden walls, not onlie because my bees love it, but because it is the herb sacred to remembrance, and, therefore, to friendship; whence a sprig of it hath a dumb language that maketh it the chosen emblem of our funeral wakes and in our burial grounds”.

During the Middle ages in Europe and Mediterranean, it was a myth that Rosemary dispels negativity. Ritually, it was tucked under the pillow to remove nightmares and evil spirits. At one time, it was customarily burnt inside the house to keep away black plague. Based on those belief, Rosemary becomes an essential ingredient of the incense burnt for cleaning sacred places including the church. The herb and flower are also considered as a sign of prosperity. The merchants of 16^th century often spread the perfume of Rosemary in the shops expecting a business prosperity. The herb with flowers is displayed in the floral wreath to bring happiness at home and in life. It is the reason, Rosemary finds its permanent place within bridal bouquet, headpiece and dress as well. In some places, the guests are also handed over the branches of Rosemary for future remembering of the occasion. The herb and flower display sign of a happy matrimony, forever to be remembered. Besides wedding or any happy events, it is also directed in honoring those who are dead. It is often laid over the coffin or even on the tombstone for the remembrance. Shakespeare mentioned about Rosemary to be presented during Juliet’s unfortunate death. In Hamlet he further mentioned when Ophelia appeals Hamlet with “There’s Rosemary, that’s for remembrance, pray you love, remember.” Historically, the herb has been always associated with the memory and recollection believing to be a memory enhancer.

Health benefits of Rosemary: The herb has large reserve of anti-inflammatory components. The majority are identified to be anti-oxidants that also helps improve circulation and enhance the immune system by scavenging toxic free radicals built up inside the body. It is said that Rosemary helps indigestion, but no scientific evidences are ever brought in its favor. Studies have convinced that components of Rosemary oil enhance memory, improve concentration and accuracy also the overall performance as well. In doing so, aromatherapy is often claimed effective against the progression of any dementia. The medicinal use of Rosemary either to prevent or to arrest the progression of Alzheimer shows a great promise. Studies further claimed that Rosemary can retard the aging of brain. One of the identifiable component is 1,8 Cineole, a cyclic ether monoterpene that acts as a potent inhibitor of Acetyl choline esterase and Butyl choline esterase. Seemingly, it produces potential impact on cognitive function or dementia. Additional reports also indicate that other aromatic ingredients produce synergistic effect on that aspect. The presence of Carnosic acid, a di-terpene is also seen to produce beneficial role on brain along with others by scavenging the free radicals generated within the neurological system thus preventing any possible damages within brain particularly after suffering a stroke.

Regarding cancers, several reports indicate that Rosemary extract prevents metastasis of breast cancer and leukemia cells. The anti-inflammatory components, possibly antioxidants could be the underlying factors behind this anti-cancer effect. Interestingly, reports further indicate that the extract can reduce the formation of cancer causing agents produced during barbecuing of beef patties. The fact is noticeable regarding other foods also. Presence of rosmarinic acid inhibits the generation of mutagenic heterocyclic amines, β – carboline analogs like harmane (methyl – β carboline, MAO inhibitor) and norharmane (β – carboline, inverse agonist of benzodiazepine receptor) by its antioxidative action. Around 375^◦F Rosmarinic acid reduces the generation ~ 80 % whereas at 450^◦F it is ~ 50 %.

Macular degeneration or age related macular degeneration is a disease of the retina that commonly affects many people over the age of fifty bringing blindness. Research shows that Carnosic acid, a major component of Rosemary either prevents or lowers the progression of this destructive disease.

Culinary use: The leaves are solely used for flavoring the foods, particularly during roasting of beef, lamb, pork, chicken or turkey. Dried leaves are traditionally used in the Mediterranean cooking. It has its own characteristic aroma which adds pleasant flavor to the food.  Besides adding flavor, the herb prevents generation of mutagenic components often produced during the roasting of foods.

Medicinal components and their biological role: The plant is an enticing spice as well as a wonderful medicinal herb. It has large reserve of phytochemicals, which are seen beneficial for health. About 38 phytocomponents have been identified within its essential oil. Obviously, the contents vary according to its birthplace, soil and climate. The most notable ones are: 1,8 cineol (~ 37 %), Camphor (~ 17 %), α – pinene (~ 9 %), α – terpinol (~ 8 %), Camphene (~ 6 %), Borneol (~ 5 %), Limonene (~ 3 %) and p – cymene (~ 2.5 %). In addition to those there are few important which needs to be mentioned because of their physiological importance eg, Rosmarinic acid, Carnosic acid, Ursolic acid, Betulinic acid and Caffeic acid.

(R -) Camphor – a bicyclic monoterpene exists (~ 20 %) in Rosemary oil. It activates TRPV1, TRPV3 and TRPM8 receptors. But only the activation of TRPM8 causes the cooling sensation. Additionally, it produces tachycardia, skin flushing, vasodilation and perspiration.

α – Pinene – a monoterpene. It acts as bronchodilator, anti-inflammatory (via PGE1), antimicrobial, acetylcholine-esterase inhibitor (acting as memory enhancer) and positive modulator of GABA_A receptor (inducing sedative action).

α – Terpineol – a monoterpene. It has strong antifungal and antimicrobial effect. It also acts as anti-cancer agent by suppressing NF- κβ pathway. Its anti-inflammatory effect is due to the blocking of pro-inflammatory cytokine IL-6. The compound also shows anti-proliferative property toward cancer cells.

Camphene – a monoterpene. The compound shows multiple biologic properties like, antifungal, antibiotic, analgesic, anti-nociceptive, anti-inflammatory and analgesic.

Borneol – bicyclic monoterpene. It has beneficial action while preventing cerebral ischemia.

Limonene – Cyclic monoterpene heavily used in the field of cosmetics and food flavoring agent. It is a botanical insecticide also relieves heartburn and gastro esophageal disease.

p– Cymene – It is alkyl benzene related to the monoterpene. It has large number of medicinal properties eg, anti-oxidant, anti-inflammatory, anti-nociceptive, anxiolytic, anti-cancer and antimicrobial.

Ursolic acid – Pentacyclic triterpene. The compound has immense number of biologic properties: A) Blocks proliferation of cancer cells by inhibiting STAT 3 activation pathway; B) Induces apoptosis; C) Inhibits JNK expression and IL-2 activation of JURKAT leukemic T cells; D) Aromatase inhibitor (blocking estrogen production); E) Helps nerve repairmen after the injury; F) Helps cognitive repair by blocking p38 / NF-κβ mediated inflammatory pathway; G) Helps repairing oxidative damages inside the CNS; H) Helps regenerate liver cells after partial hepatectomy; I) Boosts immune system; J) Enhances pancreatic β – cells function helping diabetes patients.

Betulinic acid – pentacyclic triterpene. It is a widely known antitumor agent. In addition, it has other medicinal role: A) Anti-retroviral action; B) Anti-malarial; C) Anti-inflammatory; D) Anti-cancer (by inhibiting Topoisomerase).

Caffeic acid – dihydroxy cinnamic acid. It is found in the coffee and many spices. It has few potential medicinal role eg, antioxidant, Anti-inflammatory and anticancer.

Adverse side effects and drug interactions: The herb is normally very safe. But if taken at high doses particularly when using the extracted oil that may trigger potentially serious side effects which is rarely observed. Those effects include, vomiting, spasms, pulmonary edema and coma. Further, pregnant women should not use it at high doses which may cause miscarriages. The herb also interacts with several medications used for common ailments: A) anticoagulant drugs used for blood thinning – Warfarin, Aspirin and Clopidogrel; B) ACE inhibitors to treat high the blood pressure – Lisinopril, Fosinopril, Enalpril and Captopril; C) Diuretics – Furosomide and Hydrochlorothiazide; D) Manic depression – Lithium.

 

Vanilla

General features: It is pleasant smelling orchid belonging to the Orchidaceae family of Vanilla genus. The plant is a tropical flowering vine (50 – 75 ft height) that grows small bean pods 6 – 8 inches in length and 1/3 inch wide. The word Vanilla originates from the Spanish word ‘Vaina’ signifying pod. It is seemingly the second after Saffron according to price among the spices. The genus produces 110 species belonging to the orchid family. The commonly used one is flat leaved termed as Vanilla planifolia, a native of Mexico. Its use in South American countries date back to the Aztec civilization. Herman Cortes, the famous Spanish conqueror introduced this pleasant-smelling spice along with the other precious one, chocolate to the European society around 1520. The bean pods which are ~ 6 inches long are the number one category whereas those over that limit, fall into the second-grade. The developed vine produces ~ 100 pods in a year maturing around 8 – 9 months after flowering. Interestingly, if too many flowers undergo pollination at a time producing excessive number of pods that might bring death to the vine. The green beans are normally harvested at the onset of sunrise then wrapped inside the warm woolen blankets keeping for fermentation under the warm midday sun. Later they are preserved inside a metal lined air tight box. This is called ‘sweating or curing process’ that lasts for few weeks. In that way, vanillin is produced after undergoing degradation by the enzyme, Glucosidase which removes the glucose moiety while producing respective products.

 

A matured vine of five years old produces 3.5 lbs beans that increases to the extent of maximum ~ 7lb in next two years. Only three major species of Vanilla are used all over the world. The one of major use is Vanilla planifolia, the Mexican variety that grows better in Madagascar and Indonesia. The others are Vanilla tahitensis and Vanilla pompona which also grow in tropical climate in the Islands of Indian ocean, West Indies and Central and Southern American countries. Madagascar produces more than two thirds (2.9 K tonnes) of the entire world supply and the quality is supreme. Indonesia picks the next (2.3 K tonnes) and later comes Mexico (0.6 K Tonnes) and Papua New Guinea (0.5 K tonnes). The major aroma producing components are synthesized inside the fruits. Each flower produces just one pod. The interior of pod consists of large number of tiny seeds (0. 3 – 0.5 mm in diameter) marinated in oil. They undergo self-pollination since they carry both male (anther) and female (stigma) organs. But self-pollination is prevented inside the flower by a naturally separating membrane dividing the organs. The pollination is only carried out by the mountain bees, Eulaema or hummingbirds. This event once provided Mexico a special advantage that lasts almost 300 years until hand pollination came into the practice, invented by Charles Morren in 1836, a Mexican botanist. The process is now followed everywhere even in Mexico which has been improved significantly. Numerous attempts to grow this orchid to grow vanilla commercially in European climate are failed. The plant severely needs tropical climate to grow. The main flavoring agent is Vanillin (m – methoxy- p – hydroxy benzaldehyde) which is produced synthetically in recent days for numerous culinary and cosmetic needs.

History and mythology: History reveals that Totonac, the early inhabitants of east coast of Mexico, present day Veracruz first started the cultivation of Vanilla. Totonac mythology tells that Princess Xanat married a mortal disobeying her father’s objection and alongside fled in the forest with lover. Following the capture, both were executed. The myth says, when their blood touched the soil, there grows this sweet-smelling vine, Vanilla. The legend indicates that this sweet and pleasant smell is a sign of immortal love. In 15^th century, Aztecs conquered that place and initiated its cultivation since by that time they also developed the taste as well. Then the Totonac people were used as slaves for its cultivation. Until the 19^th century, Mexico was the largest producer. At the beginning of 19^th century a bunch of French entrepreneurs shipped Vanilla fruits and started its cultivation in the islands of Mauritius and Reunion. Since the technique of hand pollination was already in progress so this orchid traveled to the other tropical islands for cultivation like Seychelles, Madagascar, Indonesia and Comoros islands. In time, Madagascar becomes the highest producer and Indonesia stands to be the next.

Uses: For culinary purposes, Vanilla is normally employed for baking or making ice creams, puddings, chocolates, liquors and soft drinks. Its other use is found in the field of cosmetics. But it finds some medicinal uses also. In traditional or folk medicine, Vanilla is applied to treat the fever or hysteria. It stimulates brain increasing energy and promoting the sexual drive thus acting as an aphrodisiac. In the past around 16^th or 17^th century, European apothecaries used Vanilla oil as an antidote for poisoning, stomach complaints and aphrodisiac. In old days in many places of Africa people used Vanilla for the same purposes. It shows antispasmodic and calming sensation. It is also used as emmenagogue, antioxidant and anti-depressant. Additionally, Vanilla oil has further beneficial roles. It regulates menstruation, relieve nausea, lowers anxiety, stress, insomnia, healing wounds, induces sleep, encourages dreaming and enhances libido. As per other uses, the sweet warm smell of Vanilla oil is often exploited as a perfume. It offers intense sense of relaxation for deep sweet scent enabling to penetrate the nervous system. It is used in aromatic candle or mixed with the humectants to use in moisturizing cream.

Chemical components: The major composition of vanilla fruits is: water ~ 30 %, various mineral salts ~ 3.0 – 5.0 %, Carbohydrates ~ 20 %, Lipids ~ 8 – 10 %, Vanillin ~ 1.5 – 3.8 %. Besides Vanillin, the herb produces reducing monosaccharides, sucrose and oil. The chemical ingredients of oil are Vanillin (~ 85 %), Eugenol, Piperonal and Caproic acid. Among those, Vanillin is the actual flavoring agent in the Vanilla bean. In addition to that, the other flavoring agents are p – hydroxy benzaldehyde and p – hydroxy benzyl methyl ether. The other chemical components are Furfural, Hexanoic acid, Methyl Cinnamate and Iso-butyric acid. In 1858, Vanillin was isolated from the Vanilla beans by the French chemist, Gobley. Afterward it has been successfully synthesized in the laboratory. In recent days, majority of it is a synthetic product.

Medicinal effects: The medicinal actions of Vanilla components mostly rely on anti-oxidant property that efficiently prevents any DNA damage due to ROS and NOS productions caused by the infections or other diseases furthering many catastrophic ailments that includes cancers or tumors. Studies already indicated that Vanillin has potential anti-carcinogenic action. It kills cancer cells also prevents them to be metastasized.  Concerning the cardiovascular role, Vanillin reduces cholesterol level. It lowers the risks of blood clotting and along side behave as an anti-inflammatory component. The combined effects help reduce the chance of atherosclerosis. Because of the anti-oxidant role, it stimulates normal growth preventing the breaking down of cells or tissues. As per further actions, owing to anti-bacterial nature it protects the immune system, lowers stress and helps recover the body from any injury or ailments. The components of Vanilla also behave to be an antiphlogistic, effective enough to reduce fever and inflammation. In that regard, Eugenol and Vanillin are noticed to be the potent components because of the anti-infection property. The use of Vanilla both in food or cosmetics stimulates secretion of sex hormones like testosterone and estrogen that promotes the arousal reviving sexual performance. From the very ancient times, Vanilla is considered as an aphrodisiac. The oil of this herb helps recuperate dysfunctionality, impotency, frigidity or loss of libido helping sufferers getting out of the problems. The major component Vanillin is also a strong anti-depressant whether consumed orally or as olfactory odorant. It puts everyone in good mood irrespective of the ages, from toddlers to adults. Vanilla also induces sedative effects. Vanilla oil generates calming and relaxing sensation on nervous system relieving anxiety, anger, restlessness and mental stress, helping lower the blood pressure. It also provides good night sleep for its tranquilizing role. It recently indicates that Vanillin has a potent role to prevent or resist the progression of neurological diseases like Alzheimer’s dementia and even Parkinson’s disorder.

Pharmacological role of Vanillin on Alzheimer inhibiting amyloid aggregate formation: The intriguing observation in recent days shows that Vanillin or any phenolics with similar structural moiety enables prevent amyloid aggregate formation during non-enzymatic glycation restraining the production of advanced glycation end products (AGE). Amyloid aggregation or AGE production is the result of protein glycation. The event is associated to the mechanisms behind several diseases like, retinopathy, neuropathy, nephropathy, macro-vascular diseases, Alzheimer, cataract and aging. The amyloid formation is a tendency noticed among the most proteins.  In that act, blood proteins or peptide hormones like insulin is no exception. It is observed that insulin also undergoes amyloid fibril formation at the site of injection, known as injection amyloidosis. The incidence creates a hard-subcutaneous mass which often triggers the immune responses causing impairment in insulin absorption. Vanillin strongly resist that process of amyloid formation of human insulin. As an added factor, glycation by glucose is very much associated with the development of diabetic complications. Under physiologic condition glucose undergoes degradation to glyoxal or methyl glyoxal, which is a key factor in the path to form glycated protein production bringing conformational changes to secondary structures eventually facilitating the plaque formation. The amyloid fibrils consists of β – sheet structure that runs perpendicular to the fibril’s axis. They are formed by stepwise events eg, oligomerization, nucleation and growth phase. Among the steps, nucleation event is the slow one whereas growth phase turns to be the fast. It has been observed that the level of methyl glyoxal (CH₃COCHO) production is increased within cultured red blood cells along with the increment of glucose in the media. The incident turns identical to the enhanced production of methyl glyoxal observed in blood, kidney and lenses during hyperglycemia which has been verified even in the case of experimentally induced diabetic animals. Experiments further indicate that methyl glyoxal undergoes reduction by Vanillin inhibiting the generation of fibrils or AGE. It is hypothesized that Vanillin traps methyl glyoxal directly. Below are the chemical steps identified for AGE formation.

Natural production of glyoxal or methyl glyoxal – The production of reactive di-carbonyl is the important factor in overall process.

Production of methyl glyoxal from the Amadori products –

Pharmacology of Vanillin receptor –  The sweet and pleasant smell of Vanilla originates from the chief ingredient, Vanillin. The compound activates Transient receptor potential channel – V1 and – V3 (TRPV1 & TRPV3). But the major interaction is with TRPV1 which is formerly known as Vanilloid receptor – 1 (VR1). It is a nonselective cation channel with high Ca⁺² permeability. It is expressed in the population of sensory neurons. The primary sensory afferent neurons on trigeminal ganglia transmit sensory information bringing awareness about chemical surroundings to the brain. Numerous components act as stimuli including the olfactory odorants which interact with sensory neurons of the trigeminal ganglia. That sensory elements belonging to the trigeminal area are liable for the perception of smell causing changes in membrane potential. In course of interaction with Vanillin, the dose-dependent depolarization has been observed. Using specific antagonists, it is identified that Vanillin largely stimulates TRPV1and in that course, it subsequently inhibits the K⁺ channels, TASK1 and TASK3. This is perhaps the underlying mechanism behind smell perception of Vanillin via the trigeminal ganglion neurons.

Tridax Procumbens / Bisalya karani / বিশল্যকরণী

General features: Tridax Procumbens (TP) is a perennial flowering plant of daisy / Asteraceae family belonging to the Tridax genus. The plant, TP is a widespread weed which is native in tropical and subtropical regions around the globe (Africa, Indian subcontinent, Latin American nations). In English it is commonly called Tridax daisy or Coatbuttons. In Bengali and Oriya language it is named as Bisalya karani (বিশল্যকরণী). Despite being registered as a weed in the list of US department of agriculture (USDA), the plant has immense medicinal values especially considering its wound healing, anti-inflammatory, anti-pyretic role and other beneficial role. In many South East Asian Nations, it is listed in the category of medicinal herbs. TP / Bisalya karani earns its eminence for displaying powerful healing act, which has been described in the great Hindu epic, Ramayana. The plant grows wildly throughout India mostly in the meadows, croplands, lawns and roadsides. It expresses white flowers having bright yellow color at the center with daisy like appearance that normally grows ~ 8 inch in height. The leaves are arrow shaped, plump with jagged edge. The plant bears small sized fruit covered with hair with white feathery pappus (like calyx). TP is highly invasive since it produces large number of achenes (like seeds), which can be carried far away by the wind. In several African nations the fresh green leaves are cultivated for use as vegetable and fodders. The leaves are eaten after cooking considering its high nutritional values due to high protein (34.6 %), carbohydrate (51.3 %) and moderate lipid (6.1 %) and fiber (6.1 %) content (% in terms of dry weight). The plant possesses high potassium (32.0 mg / Kg) along with innumerable phytochemicals which are expansively beneficial for health. In Guatemala, it is also used in treating wounds, parasite infections and various other diseases like in gastric and respiratory problems.

Folk use: The leaf juice has antiseptic, insecticidal and anti-parasite properties particularly applicable toward the drug resistance malaria and leishmania also in case of dysentry. It is often used in the villages of tropical and subtropical regions to cure skin infections. As a precious folk medicine, it is used to cure wounds or preventing bleeding. In recent days, studies have indicated its numerous therapeutic actions like, antiviral, antibiotic, wound healing, anti-inflammatory, anti-ulcer, curing anal fistula and hemorrhoids. The plant is exceedingly adored in the Indian state of Orissa and Tamilnadu. It is heavily cultivated for the sake of using as folk medicine. The further use of TP has been noticed to be an effective anticoagulant also for treating any boils and blisters. Below is the table for its use in different countries around the world.

Traditional / Folk uses in different countries

Country / Region	Extract or Preparations	Diseases used for
India	Leaves – Either juice, paste or dry leaves. Ingested orally or applied topically.	Controlling hemorrhages, Inflammation, jaundice, Diabetes, diarrhea, hair loss and helping wound Healing.
Africa	Generally, the entire plant is blended with Other herbs using water and common salt.	Treating mastitis within dairy animals.
Ghana	Aqueous extract	Anti-malarial, Anti-bacterial, Anti-plasmodial, And wound healing.
Nigeria	Dried whole plant	Fever, Typhoid, Cough, Back ache, Stomach Ache, Diarrhea and Epilepsy.
Benin	Dry whole plant	Livestock feed.
Togo	Dry leaves	Dressing wound, pain, malaria, abdominal Problems and gastrointestinal mycosis.

Mythology: The use of TP / Bisalyakarani first came into the lime light from legendary mythological saga of Ramayana, the most celebrated epic belonging to the Hindus of India, written cumulatively between 6^th to 11^th century AD. In that saga, the use of Bisalyakarani was overtly mentioned that possibly unveiled the popular use. The mythology illustrates that during daring rescue mission by Laxman for his brother’s wife, Sita from the garrison of Sri Lankan emperor, Ravana, he was grossly hurt by the arrow from eminent archer, Meghnad, heroic son of Ravana. Hanuman, the assistant of Laxman sought medical advice from Sushena, the royal Sri Lankan physician. Sushena sent Hanuman to the Himalayan mountain for procuring four herbs, Mritasanjeevani (for restoring life), Bisalyakarani (for healing the wound of arrow), Sandhankarani (for restoring the skin) and Savarnyakarni (for restoring the skin color at the place of wound). But owing to his ignorance, Hanuman could not identify anyone of them within the enormous herbal stalk grown over the mountain top. Instead, he carried the entire hill top with him. While being unable to carry further, he dropped the load before reaching to the Sri Lanka which in recent days is located between Balangir and Bargarh district in the state of Orissa, India. Sushena came forward and being an outstanding physician, he identified the herbs and successfully applied them.  Following that course of treatment, Laxman healed and survived which eventually helped afterward bringing down the Sri Lankan empire of Ravana. Thus, Sita has been rescued unharmed. Among those healing herbs, Bisalyakarani was described to be the prominent one. The mythology intimately entangled with the then history, in fact indicates an expedition occurred to the south carried out by a northern ruler in amorphous ancient India. In that event Bisalyakarani / TP was discovered which in turn found numerous beneficial applications later in the field of folk medicine. In village remedy, the juice or paste made of fresh leaves is often applied directly to the wound helping expedite the healing process also protecting the wounded site from inflammation and possible infections.

Chemical components and medicinal effects: In general, the herb contains a large reserve of alkaloids, phytosterols, hydroxycinnamates, lignans, flavonoids carotenoids, various terpenes (higher amount α and β – pinenes) and tannins. The total flavonoids content is ~ 6.5 g / Kg of dry leaf. About 23 flavonoids have been detected. The leaves also had moderate levels of tannins (0.8 g / Kg), hydroxycinnamates (0.6 g / Kg), phytosterols (0.3 g / Kg) and low benzoic acid derivatives (0.03 g / Kg), lignans (0.08 g / Kg) and low carotenoid contents (0.001g / Kg). The total alkaloid content is noticeably high ~ 10.2 g / Kg in the leaves. Below is the table for the major ingredients that are estimated to be in highest level.

Components of maximum content

Category	Name	Content (Maximum level)
Alkaloid	Akuammidine Voacangine Echitamine	70.4 g / Kg 16.9 g / Kg 5.1 g / Kg
Flavonoids	Kaempferol (-) Epicatechin	11.5 g / Kg 8.2 g / Kg
Phytosterols	Stigmasterol	2.1 g / Kg
Tannins	Tannic acid	8.2 g / Kg
Carotenoids	Lutein	0.009 g / Kg
Hydroxycinnamates	Caffeic acid	5.8 g / Kg
Benzoic acid derivatives	Ferulic acid	0.2 g / Kg
Lignans	Galgravin	0.6 g / Kg

Alkaloids- Interestingly a large quantity of indole alkaloids is produced both in leaves and stems of the plant. About 39 alkaloids are isolated and identified so far from the aqueous extract. It is believed that there could be more unidentified ones in the pedicle and buds. The unknown alkaloid fraction extracted from those parts shows strong anti-microbial property against Proteus mirabilis (microbe helping kidney stone formation) and Candida albicans (causing Yeast infection in guts and vagina). The extract from bud shows activity against E. coli and Trichophyton mentagrophytes (fungus making ring worm). Experiments indicate that these alkaloids exert quite a different physiologic effects. For example, Akuammidine acts as opiate agonist that binds with µ -, δ – and κ – receptors having the K_i = 0.6, 2.4 and 8.6 µM / L. The in vitro bioassay shows that its actions can be antagonized by using Naloxone or specific µ – receptor antagonist (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2). Akuammidine also displays antibacterial, antifungal, anti-malarial, anti-inflammatory, hypotensive, anti-depressant, muscle relaxant and local analgesic properties. On the other hand, Voacangine shows potent anti-angiogenic action. Angiogenesis, the formation of new blood vessels is the key factor in the path of tumor growth. The development of anti-angiogenic compound is one of the ways to control the progression of solid tumors and metastasis. Voacangine isolated from numerous plant sources including TP is a novel anti-angiogenic compound enabling to stop angiogenesis in vivo and in vitro experiments (IC₅₀ ~ 15 µM) without affecting the normal cells. Additionally, besides its anti-angiogenic action, the compound also shows strong anti-oxidant and anti-acetyl-cholinesterase property that may help control the Alzheimer’s progression. The compound exerts several other actions eg, CNS depressant, anti-convulsive, anti-pyretic, analgesic, anti-mycobacterial, cardio-vascular toning and local anesthetic. The other significant indole alkaloid, Echitamine also shows few important biologic effects while acting as anti-cancer, anti-bacterial, antitussive and anti-fertility component. In addition, it also exerts diuresis, CNS depression, hypotensive and anti-epileptic effects.

Flavonoids – They are everywhere, in leaves, buds and stems. They can act as anti-coagulant, anti-fungal, hair tonic, prevents various bronchial problems, diarrhea, dysentery and wound healing. The TP leaves contain high level of flavonoids, ~ 25 in total. All of them have beneficial role on health. As shown in the table, besides expressing large quantity of kaempferol (~ 18 %), epicatechin (~ 8.2 %) and biochanin (~ 8.0 %), the leaves also have other flavonoids eg, (+) catechin, apigenin, naringenin, quercetin, genistein, butein, gallo-catechin, luteolin, myricetin, robinetin and many others in moderate or lesser amount. Additionally, there are few new components recently identified. One of them is Procumbenetin, a glycosyl linked flavone which has shown strong antioxidant and hypolipidemic action on animals. The compound and its analogs also have ability to prevent formation of kidney stone by blocking Ca and oxalate deposition inside the kidney. On the other hand, Procumbenetin does not express antifungal activity. These flavonoids can regenerate damaged β – cells in the pancreas. It has been noticed among the diabetic animals that daily consumption of TP juice especially the flavonoid fraction can induce hypoglycemic effect and lower VLDL and cholesterol. In general, most flavonoids provide strong anti-oxidant effect by scavenging the reactive oxygen or nitrogen species protecting from cardiovascular disorders, kidney diseases, hypertension and cancers. Luteolin shows anti-inflammatory and anticarcinogenic actions which could be due to its antioxidant actions. Like luteolin many of the flavonoids display anti-tumor effect. Some of them exert anti-angiogenesis, block metastasis, helps DNA repair and inhibits cancer cell replication also promoting apoptosis. In a way, flavonoids exert remarkable positive actions toward the health.

Tannin – The tannin (8.2 g / Kg dry weight) available inside TP is tannic acid (pK_a ~ 10) which exists in moderately high level providing strong antioxidant effect. It is water soluble polyphenol found mainly within the plant kingdom. Tannin fraction of TP offers anti-microbial, anti-carcinogenic and anti-mutagenic properties. All these effects might arise due to the strong anti-oxidant nature.

Carotenoids – The carotenoid fraction in TP is mostly Lutein (9.0 mg / Kg dry weight) which is a xanthophyll, naturally occurring carotenoids synthesized only within plants. It is a yellow pigment helping the process of light harvesting during photosynthesis. The pigmentation occurs attract the insects. Lutein protects tissues from any photooxidative damage. The consumption of Lutein prevents oxidative DNA damage because of its potent anti-oxidant action. It helps maintain epithelial tissues through the conversion to vitamin A which is a necessary factor for maintaining immunity, hematopoiesis also inhibiting the possibility of night blindness.

Lignan – The noticeable one is Galgravin. It is produced from Ferulic acid. This polyphenolic compound has versatile beneficial effects. For example, it is an anti-trypanosomal compound which is really a very prominent property since that affects many in tropical countries. Further, the compound inhibits Platelet Activating Factor (PAF) receptor binding also shows strong antiviral action toward HIV-1 and foot mouth disease.

Hydroxycinnamate and benzoic acid derivatives –  The plant expresses high extent of Caffeic acid (8.2 g / Kg dry weight) but very low level of Ferulic acid (0.2 g / Kg dry weight). Both have positive effects on health. Caffeic acid inhibits cancer cell proliferation. Like Ferulic, Caffeic acid is a strong anti-oxidant also acts as anti-inflammatory components. Caffeic acid is a natural fungicide enabling to inhibit the production of Aflatoxin. It also significantly reduces the progression of colon tumors. Caffeic acid is a precursor of Ferulic acid. The later is also strong antioxidant behaving by scavenging the ROS thus prevents DNA damages.

 

Analysis of various parts of TP plant reveals that the chemical content of all categories is high mainly in the leaves. The plant possesses innumerable compounds which has the wonderful medicinal role. Many of them are not mentioned or discussed above, eg, the alkaloid Lupanine or a diterpene Augustafolin. Lupanine acts as a cholinergic drug causing CNS depression and has the antiepileptic, oxytocic and anti-arrhythmic, hypoglycemic plus hypotensive role. On the other hand, Augustafolin is a strong bacteriostatic agent.

Pharmacological actions: The pharmacological role of TP is numerous. The compounds synthesized within TP have versatile medicinal role. They can prevent anemia, boost immune system, act as antioxidant, anticancer, antifungal, antibacterial, antiparasitic, antiviral and anti-plasmodial.

Anti-inflammatory – The anti-inflammatory action is conceivably due to its potent antioxidant effect. Reports indicate that poultice prepared by using TP leaves can reduce experimentally induced inflammation to a significant extent. The extract can also be used both orally and topically for the reduction of inflammation which is seen somewhat superior to Ibuprofen or Aspirin. Advantageously, it does not cause ulceration or create any adverse reaction which is a major concern for them.

Hepatoprotective effect – The reports on animal data using experimentally induced various liver problems confirms the impressive power of hepatoprotection by TP extract. The underlying factor(s) are appeared to be flavonoids. Additionally, animals treated with TP show no adverse effects at all.

Anti-cancer effect –  Numerous studies indicate a great promise regarding its use to reduce or prevent number of different cancers. Considerable inhibitory effects are noticed for prostate and lung cancers. The TP extract efficiently blocks angiogenesis. In addition, it also shows enhanced expression of P53 and Caspase which help induce apoptosis for the tumor cells.

Antihypertensive effect – In many areas of the world, TP is traditionally used to lower the hypertension. Studies on experimentally induced animal shows the effect being comparable to captopril. The plausible mechanism could be either due to the vasorelaxation or diuretic role of various flavonoids.

Antidiabetic action – The studies on experimental animals reveal that TP consumption acts better than Glibenclamide, a common drug used to control type – 2 diabetes that works by stimulating the release of insulin from pancreatic β – cells. But unlike the drug the herb acts by lowering the enzymatic action of α – amylase and α – glucosidase which are liable for the breaking down of carbohydrates.

1. A) Anti-microbial, B) antifungal, C) antibacterial and D) antiparasitic effect – A) Anti-microbial effect has been noticed against subtilis, B. faecalis, E. Coli and Pseudomonas aeruginosa which is presumably due to the existence of alkaloids. B) The antifungal stains that are affected are Microsporum fulcum, Microsporum gypseum, Trichophyton mentagraophytes, Tricophyton rubrum, Candida albicans and Tricophyton beigelli. But no specific fractions or compounds have been identified yet. C) The extract from TP is seen to be effective against Mycobacterium smegmatis, E. Coli, Kleibsiella sp, Salmonella group C, Salmonella paratyphi and several other types also. D) The anti-parasitic actions are against malaria, leishmania and other protozoa infections like dysentry, vaginitis, malaria and colic.

Below is the table for summarized version of various pharmacological effects of TP.

Pharmacological effects of TP

Pharmacological role	Effects	Phyto-components
Antioxidant action	Anti-inflammatory, Antioxidant & Anticancer.	Poly – phenols, Flavonoids, carotenoids and Alkaloids.
Anti-cancer action	Cytotoxicity against many Malignant tumor cells.	5, α – cholestane, monoterpenes (α and β – Pinenes).
Anti-hypertensive effect	The effect is comparable to the drug Captopril.	Suspected components are flavonoids and Alkaloids.
Hepatoprotective action	Lowering of oxidative stress. Lowering of serum aspartate Aminotransferase, serum alanine Aminotransferase, serum alkaline Phosphatase and serum bilirubin.	Suspected agents are alkaloids and Flavonoids.
Antidiabetic effect	The effect is comparable to the drug Glibenclamide.	Saponins.
Immuno-boosting effect	Increment of neutrophil percent in the experimental animals.	Possible components are tri- and sesquiterpenes.
Anti-microbial, Antifungal, Antibacterial & Anti-parasite	Already mentioned.	α – & β – pinenes, Alkaloids, Flavonoids, monoterpenes & Oxylipin.

 

The beneficial role of TP is legendary due to the existence of multitude of phytochemicals. The plant has been in use as a folk medicine for different needs in various regions of the world. Interestingly, the plant is also used as vegetable in several regions. So, including it as a vegetable in the daily diet may cure or prevent many of the illnesses.

 

 

 

Aloe Vera / Ghrita Kumari /ঘৃত কুমারী

General features: It is a shrubby evergreen perennial plant belonging to Liliaceae family of Aloe genus. The plant grows in hot and dry climate. It has been first identified in the Arabian Peninsula. About 250 or more species and a large section of subspecies are hitherto categorized botanically. Among them Aloe Vera is the important one for human use that has been noticed over a long period of time. The plant, Aloe Vera carries several different names also eg, Aloe barbadensis Mill, Aloe chinesis Bak, Aloe elongate Murray, Aloe indica Royale, Aloe Officinalis Forsk etc. In Sanskrit as well as in Bengali it is named as Ghrita Kumari (ঘৃত কুমারী), meaning a delicate virgin. As per the folk medicinal use, it is commonly believed that it has the rejuvenating power to bring back the bubbly youth within female, not just by providing only good skin but also curing the problems associated with menorrhea and others. From the time of ancient Rigveda (1500 – 1800 BC) the plant has been designated as being the sources of vigor offering sound health offering utmost vibrancy. By appearance, it is a spiky cactus xerophytes (grown with less water) with fleshy succulent leaves that grows in a decorative pattern possessing short stems. Usually, a matured plant expresses 20 – 30 leaves. Each stem grows up ~ 1 – 2 ft high displaying bright green color. The inflorescence is a dense raceme borne on a peduncle of ~ 1 ft high. The flowers are yellow – orange with pendant appearance. The flower stems grow ~ 2 ft in height. The plant reaches to the maturity in ~ 4 years that can last up to ~ 12 years while holding the ground tightly with thick fibrous roots. The small fruits are triangular and capsule like shape having numerous seeds inside. In recent days, it is cultivated for the medicinal and cosmetic purposes. It also finds uses in various beverages, ointments or lotions particularly applicable toward the burn victims. The plant is widely appreciated all over the world including far Eastern countries for the sake of its role in skin care which has been observed from a very ancient time, ~ 6000 BC. The use of Aloe is already mentioned in the millennial old Egyptian and Mesopotamian literatures especially for the skin care and laxative needs. Evidences further indicate that the plant has the capability of lowering LDL and blood glucose with simultaneous enhancement of HDL level. It can be used topically in treating the genital herpes and psoriasis. Recently, it is claimed that the plant extract can control HIV / AIDS infection. Its beneficial effects are also observed regarding rapid healing of burns, suppressing allergies while boosting the immune system, or curing any damages due to frost bite, preventing cancer in lung and preventing intestinal disorders. The central part of the leaves has thin walls holding colorless mucilaginous jelly popularly called Aloe gel. It possesses water (99 %), glucomannans, lipids, amino acids, sterols and few vitamins. Whereas underneath the skin of middle layer holds Aloe juice. It contains several chemicals of bitter taste providing powerful laxative property due to the anthraquinone content. The outer thick layer known as rind offers protective function to plant which is composed of carbohydrates and proteins involved in the transport of water, solutes and starch.

Common home uses: As a folk medicine it is still used in the home remedy for following reasons.

• Skin care
• Wound healing
• Treatment for diabetes
• Anti-inflammatory reasons
• Immunomodulatory role
• Anti-cancer effect
• Treating burns.

History of Aloe use: Countless fascinating tales exist about Aloe particularly regarding its use that can be traced back to few millennia even before the appearance of Christ. The records show that Aloe juice was commonly practiced by the women for skin care in the ancient Egypt around 6000 BC. It was defined as a sacred plant therefore as per the popular belief spread, its ‘blood’ (juice) enables to unveil the secrets of beauty, health and immortality. The legendary beauty of Cleopatra and Nefertiti has been claimed to be derived from the daily use of skin nourishing juice of Aloe Vera. Additionally, in ancient Egypt, even the dead were embalmed by using the Aloe juice for its antibacterial and anti-fungal properties. The Egyptians used to believe strongly that by preventing the decomposition of cadavers, dead can earn the eternal life. They defined Aloe Vera as being the ‘plant of eternity’. Its anti-inflammatory effect was first documented in the ‘Papyrus Eber’ (Ancient Egyptian medical practice journal documenting the use of various herbs written on the Papyri) ~ 1550 BC. The written record of Aloe Vera use on a clay board was first appeared in the oldest Sumerian city, Nippur of Mesopotamia (recent day Iraq) around 2200 BC. At that time, it was a folk belief that any illness is an act of devil capturing the human body. So Aloe being a divine plant possesses the power to exorcise that demonic action. The use of Aloe for healing wounds during wars was routinely performed by the soldiers of Alexander the Great (350 – 320 BC). It is for which Aristotle once convinced Alexander to capture the island, Socotra (Archipelago in the Arabian Sea under recent Yemen) that had the large groves of Aloe which would satisfy the medical needs of the wounded warriors. Afterward around ~ 50 BC, following the Egyptians and Romans, its use turned intensely popular. The famous Greek naturalist Dioscorides mentioned Aloe Vera highly in his teaching books on pharmaceutics and plant therapy, which he compiled during his extensive travel in the orient. Aloe was his favorite healing plant. He prescribed its juice for numerous physical problems like, treatment of wounds, intestinal discomfort, skin irritation, gingivitis, sunburn, acne, hair loss and arthralgia. Its use in Chinese medicine was recorded by Marco Polo. In ancient Japan, it was known as “Royal plant” and its juice was consumed by the Samurai for maintaining good health. The use of Aloe Vera has been broadly described in “Rigveda” of ancient India in the name of “Ghrita Kumari” for its beneficial role on health particularly for maintaining acne free moist and glazy skin. Aloe was also quite familiar within native Indian tribes of North America according to the 16^th century record. Natives used to apply its juice particularly on skin for repelling the insects. They also consider it as a holy plant for its numerous beneficial effects on health. The European history indicates that Columbus was carrying Aloe Vera growing in pots onboard his armada during the expedition. The expedition helped spread its use. In 16^th century, Jesuit monks trained people for the use and also helped widening its cultivations for the sake of healing wounds. The Maya Indians in southern hemisphere of American continent labeled the plant juice as a “Fountain of Youth” for its invigorating role on health and beauty. In modern days, it is used for both medicinal and cosmetic needs.

Importance of Aloe Vera gel: The gel is widely famed for its beneficial role to control various ailments due to numerous chemical contents. The major active agents identified are anthraquinone derivatives and polysaccharides. Usually, the anthraquinones are famously known for their laxative actions. Among the polysaccharides, the notable one is Acemannan. It is a large (Mw ~ 1700) hydrophilic mucopolysaccharide connected via the β – 1- 4 glycosylated linkage having D – mannoacetate monomer. The compound has immunostimulant, antiviral, antineoplastic and gastrointestinal role.

The combined action of those ingredients within gel promotes the healing of numerous wounds. Besides healing wounds, it also has anti-inflammatory, antibacterial, antiviral, Gastroprotective, antifungal, antioxidant, antioxidant, laxative, immune stimulant and hypoglycemic role. The recent clinical evidences show that Aloe gel quickens the healing of versatile wounds, from burn to frostbite. It also lowers LDL while enhancing the HDL level in blood. Additionally, it reduces the blood glucose level, prevents / cure genital herpes, psoriasis, papilloma virus, seborrheic dermatitis, xeroderma, mouth ulcers and lichen planus. Besides its topical applications on skin the oral ingestion is frequently allowed preventing or curing various health problems.

Chemical contents: The different sections of plant is loaded with numerous chemical components. Varieties of medicinal products and cosmetics are prepared using the gel collected from the inner part of leaf. The outer leaf pulp (see the picture) produces yellow latex which is extremely bitter in taste due to the existence of anthraquinone like compounds, Aloin, Aloe-emodin and others. This part of the leaf produces strong laxative effect due these compounds.

Aloin exerts intestinal contractions by enhancing peristalasis especially in colon inducing severe bowel movements. The compound opens up Cl^– ion channels situated on the colonic membrane preventing water reabsorption of colon within the gastro-intestinal tract that essentially makes the stool softer. The combined effects of contraction and prevention of water reabsorption provides strong laxative effect. It also causes uterine contractions so any products of Aloe vera should be avoided by pregnant women. Similar role is noticed for Aloe-emodin. But Aloe-emodin also has strong anti-viral effect particularly against Herpes simplex virus 1 & 2.

The inner core pulp has various ingredients, proteins, lipids, carbohydrates, amino acids, vitamins, enzymes, small organic compounds and inorganic minerals. Considering the overall weight, the water content of fresh pulp is ~ 99.5 % whereas the rest, 0.5 % consists of solid ingredients. As per dry weight concern, polysaccharides ~ 55 %, sugars ~ 17 %, minerals ~ 16 %, proteins ~ 7 %, lipids ~ 4 % and phenolic components ~ 1 %. Often the seasonal variations are noticed in those levels. Table below shows the different chemical ingredients in the leaf.

Components	Composition
Water (~ 99.5 %)
Sugars	Monosaccharides – Glucose, Fructose, Mannose, L- rhamnose, Aldo-pentose. Polysaccharides – Glucomannans
Anthraquinones	~ 12 anthraquinones exist. Important ones are: Aloin, Aloin-emodin, Isobarbaloin, Anthranol, Emodin, Ester of cinnamic acid, Chrysophanic acid, Aloetic acid and Resistanol.
Proteins	~ 0.07 %. Lectins and lectin like substances.
Enzymes	Cellulase, Aliiase, Peroxidase, Alkaline phosphatase, Amylase, Carboxypeptidase, Catalase, Cyclooxidase, Cyclooxygenase, Lipase, Superoxide-dismutase, Bradykinase.
Vitamins	A, C, E, B1, B2, B6, B12, Niacin, β – carotene, Choline & folic acid.
Steroids	4 plant steroids. Campesterol, Lupeol, Sistosterol & Cholesterol.
Essential oil	Tridecanoic acid, Phytol, Oleic acid, 1-octanol, Squalene, Butyl-heptadecyl ester, 9,12,15,-octadecatrienoic acid ester, Allyl- Pentadecyl ester, Eicoane, 9-octadecenal, Di-dodecyl pthalate, Hexyl Pentadecyl ester, α – tocopherol and some others.
Organic fatty acids	N – hexadecanoic acid, Oxalic acid, 9,12-octadecadienoic acid (Z,Z), Arachidonic acid, γ – linoleic acid, Gibberlin, Malic acid, Lactic acid, Succinic acid, Salicylic acid, Uric acid etc.
Minerals	10 – 25 % of the dry matter. K, Na, Cl, Ca, Mg, P. Trace elements Cu, Fe, Zn, Mn, Al, Se, Cr, Pb, Co, Ba.
Plant hormones	Auxins and Gibberelin.

Auxins and Gibberelin are the plant hormones. Auxin is highly needed for the sake of cell growth and its differentiation. It is responsible for the expression of a bunch of important genes while helping their transcription. In that way, Auxins decides the arrangement or configuration and also development of a plant. Gibberelin controls the growth and other developmental processes that includes elongation of stems, germination, flowering and induction of various enzymes within plant cells.

Significant pharmacological roles: Several common pharmacological actions have been cited which are already clinically proven.

Anti-inflammatory effect – In general inflammation is caused by an injury. As per the etiology, it is a collection of biological reactions expressed as swelling, edema, pain, heat, redness often leading to loss of functionality. Sepsis on the other hand is a life threatening event caused by unrestrained activation of inflammatory pathway imposing multiple organ failure leading to the fatality. In all cases, the use of Aloe Vera improves the situation. It inhibits leucocyte cell adhesion subsequently the generation of inflammatory cytokines (TNF – α, IL – 1b and IL – 6), PGE₂, inducible nitric oxide synthase (iNOS) and COX-2 mRNA expression. The gel blocks the Arachidonic acid pathway to produce PGE₂. The responsible compounds are identified to be Aloin and Aloe-emodin.

Anti-cancer effect – The Aloe extract shows positive effect in treating the cancers. Aloe gel exerts chemopreventive and anti-genotoxic effects on Benzo[α]pyrene-DNA adducts. In addition, lectins and polysaccharides particularly, Acemannan shows reduction of tumor burden, shrinkage and necrosis consequently prolonging the survival rates among the animals. The stimulation of immune system has been identified to be the major cause. Some also verifies that disruption of mitochondrial membrane potential, release of cytochrome C and activation of Caspase 3 by the Aloe – emodin could be the underlying factor behind this anti-tumor effect.

Effect on burn and wound healing – The rapid rate of wound healing by Aloe gel is a noteworthy fact which is known for a very long time. It is seen to be effective even in the case of second degree burns which has been verified by numerous animal experiments. The major contributory factor identified is Acemannan, β – (1, 4)-acetylated polymannose. The compound stimulates the expression of VEGF and other related factors like Keratinocyte growth factor -1 and simultaneously levitates the production of type – 1 Collagen. It is particularly beneficial for the oral wound. Besides Acemannan, Aloe extract also possesses multiple pro-angiogenic components. The notable one is β – sitosterol which enhances the expression of various proteins and growth factors (VEGF, VEGF receptor Flk-1, blood vessel matrix laminin & von Wilde Brand factor) helping increase the progression of angiogenesis. The reports from various animal research further has convinced that partial thickness burns treated with Aloe gel heals faster that the silver -sulfadiazine.

It has been observed that delaying of wound healing is a crucial problem for patients underwent radiation treatment or subjected to any irradiation. Clinical studies showed that Aloe Vera can expedite the healing process in this situation. The treatment with Aloe significantly increases the production of several growth factors like bFGF and TGF-β-1.

Anti-diabetic effect –  Multitude of evidences indicate that oral consumption of Aloe juice reduces the fasting glucose level and glycosylated hemoglobin (HbA_1c). Some further claim that Aloe also lowers the LDL, total cholesterol and triglyceride. Experiments indicate that antioxidant effect of polyphenolics, flavonoids, vitamin C and E is majorly liable behind this event. Additionally, Aloe juice contains significant amount of Cr, Mn and Zn which together potentiate the antidiabetic effect. Cr particularly enhances the insulin binding leading to the increased uptake of glucose into cells. It also improves glucose tolerance and decreases the fasting blood glucose level.

Miscellaneous beneficial effects – A few of them are transcribed below:

1. Microbial effect – The juice shows several microbial effects.
2. Helping vitamin C & E absorption in the body.
3. Enhancing Insulin transport across the cell membrane.
4. Enhancing the absorption of several drugs which show poor bioavailability. Example is fluoxetine, anti-depressant drug.

Adverse effects: A few adverse actions of Aloe have been noted which are related to allergic manifestations like dermatitis in case of sensitive individuals. The actions are possibly due to anthraquinone derivatives like Aloin or Barbaloin. But the existence of Aloesin in Aloe gel which is often used as skin whitening agent might cause some unpleasant actions.

Aloesin blocks melanogenesis inhibiting Tyrosinase blocking hydroxylation of tyrosine to 3, 4 -dihydroxy phenyl alanine (DOPA) and oxidation of DOPA to Dopaquinone. In that context, the oral use of Aloe should be carefully considered. Although no toxic activity has been reported so far. Further the laxative actions might lower the Potassium level. All actions are reversible. But the use of Aloe during pregnancy should be avoided.

 

Aegle marmalos / Bael / বেল

General features: The botanical name is Aegle Marmalos which is commonly known as Bael or Wood Apple in English. In Hindi or in Bengali language it is called Bel (বেল). The tree originates mainly in the Indian Subcontinent eg, India, Nepal, Sri-Lanka, Myanmar, Thailand, Malaysia and the islands like Andaman Nicobar and several others within Indian ocean. To the Hindus, it is a sacred tree including its fruits and leaves. As per the Hindu myth, the tree is a beloved sanctuary of Lord Shiva, the powerful God of peace and destruction, where under its shade He returns to meditate. In Indian villages, the tree is always noticed at the site of Shiva temple. It also grows wildly in the tropical rain forests, hills and plains of the Indian subcontinent. It can grow even in dry and adverse conditions where others refuse to survive thus being considered as a tolerant plant. The fruit starts appearing at the onset of dry season that takes nearly a year to ripe. The plant belongs to Rutaceae family and is a member of monotypic Aegle genus.  It is a deciduous, medium sized tree, 30 – 50 ft high. The bark appears to be pale brown to greyish. The stem is long and straight. If bruised it oozes clear slimy and gummy sap resembling to gum Arabic named ‘Feronia gum’ that solidifies due to the aerial oxidation when left for a long time. The sap has sweet but irritating taste. The leaves are 2 – 4 inches long and 1 – 2 inches wide. They are trifoliate, alternate and ovate having rounded base with pointed tips. The young leaves are pinkish green in color that turns dark green at the matured stage. Bael leaves are extremely sacred to the Hindu religion. The flowers are yellowish and pale green with scented sweet smell, grown in clusters. The fruit is either round or occasionally pear shaped with thick and hard cover shell having diameter of 2 – 6 inches often called Wood Apple. The shell is green but when ripened it turns yellow. The shell never splits even the fruit gets overly matured. It takes almost a year to grow and ripe and finally reaching to the size of a grape fruit. The shell can be cracked only by a hammer. Inside, there are about 15 – 20 sections filled with the orange pulp and each section has number (10 – 15) of oblong flattened seeds ~ 0.3 inch long, confined in a sack of adhesive that solidifies on drying. The yellow pulp tastes like marmalade releasing pleasant sweet-smell possessing strong astringency. It is highly mucilaginous by nature. The fruit pulp is consumed throughout India by making beverage / sherbet which is extremely refreshing in hot summer days. The drink is considered to be healthy particularly for the digestive system. In recent days squash prepared from the pulp is commercially available in the market as a bottled drink. The partially ripe fruits after slicing are preserved in caramel or sugary syrup which is popularly known as Bel Murabba in India, good for reducing any chronic intestinal problems often included in the daily life diet. Over 5000 years, the fruits, leaves and roots of this indigenous tree are used as dietary supplements or for traditional medicines following the norm of Ayurveda. Loads of ailments of diverse categories are treated by using them. Bael fruits find home uses according to the ethno-medicinal needs for treating chronic diarrhea, dysentery, peptic ulcers or respiratory problems. Its use as a laxative is widely known. These therapeutic effects are largely based on its anti-oxidant, free radical scavenging or inhibition of lipid peroxidation effects which also includes anti-parasitic, antiviral and antibacterial actions too.

There is another kind of Wood Apple or Bael, naming Liomonia Acidissima available in the Indian subcontinent which is commonly called Kod – Bel belonging to Limonia genus. In English it is called Elephant Apple. The tree is similar in height (~ 30 ft tall) with rough spiny bark. The fruits have hard shell like original Bel fruit but produce smell of citrus when crushed. The pulp is brown colored spread with white seeds and much less gummy by nature. It is a nutritious food loaded with protein, carbs, minerals (Fe & Ca), vitamin B and high level of Vitamin C. The fully ripe fruit is indeed a high calorie food (~ 50 Kcal / 100 g). The pulp is often used in making Achar or citrus drinks which is very pleasant in hot summer days. No religious story is attached to it.

Mythology: Popular legends are all over the Indian subcontinent about the Bel tree / Aegle Marmalos including leaves and fruits which are intensely associated with the Hindu mythology. Hindu folklore indicates that Bel tree is profoundly linked to the Lord Shiva. According to the Shiva Purana, traditional lore dictates that the tree symbolizes Lord Shiva himself therefore it is the most devout and holy object to all Hindus in this terrestrial domain. It symbolizes the supreme religious replica of Hindu religion, so without the Bel leaves no Puja is ever fulfilled thus ensuring its mandatory presence. The trifoliate configuration connotes three distinct acts of Lord Shiva; Creation, Preservation and Destruction, allegorically representing the divine scrutiny through His three eyes. It’s a belief that offering the Bel leaves to Shiva will eradicate any misdeeds or sins within last three births. Praying under Bel tree is a holy act bringing happiness in life. The tree is called ‘Sri-briksha’ (শ্রী-বৃক্ষ) enabling to create happiness and tranquility in life. Both in Sanskrit and Bengali, the leaf is named ‘Bilwwa Patra’, symbolizing the great ‘Trident’ (ত্রিশূল) in Shiva’s right hand executing the blissful acts of ‘Creation, Preservation and Destruction’ keeping the universe in right order. Lord Shiva seeks divine serenity while meditating under its shade. It is His most favorite place in the universe. The mythical story says that this deciduous tree is actually the creation of Goddess Lakshmi, Shiva’s younger daughter. Once out of resentment to father, she climbed up the tree showing no intention to be down any time soon. So, Shiva told her that until she is down, He will sit and continue to meditate under it. From then on, it becomes His favorite retreat even after her departure and gratification. Multitudes of folklores relating Bel tree and God Shiva are floating all over the India that astoundingly amuses both urban and rural population even these days.

Traditional health uses: The fruit provides enormous health benefits. Besides fruit, leaves and roots also have the huge medicinal role. Decoction made from the leaves removes mucus from lung and trachea in the event of cough or cold. It is diaphoretic producing perspiration helping lower the body temperature during fever. The leaves are normally useful in treating fever, abdominal pain, urinary problems, heart palpitation, dysentery and diarrhea, dyspepsia, vomiting and seminal weakness.  The root extract helps piles sufferers and prevents dysentery and diarrhea. The fruit pulp which are normally used in frequent occasions offers a great number of health benefits as shown below.

Digestion – The pulp acts as decent digestive aid and a remedy toward chronic digestive disorders thus often used to cure recurring dysentery.  The gum exudates either from branches or that resides inside the fruit, naming ‘Feronia gum’ can cure intestinal diarrhea and dysentery. It exerts laxative action eliminating chronic constipation and associated discomforts. The pulp prevents peptic ulcers and piles. The large tannin and flavin content in both fruits and leaves exert strong anti-inflammatory effect that helps prevent chronic inflammation or ulcers inside the digestive tract. It also efficiently removes any worms, fungus or parasites inside the intestine. In overall aspects the pulp helps maintain good digestive order if added daily in the diet.

Protecting liver function – The fruit is a large reservoir of antioxidant especially β – carotene (~ 60 mg / 100 g pulp) and in addition it has thiamine and riboflavin and other vitamins. Their combined effect enables to cure chronic or inflammatory problems produced within liver.

Preventing Scurvy – This life threatening disease is caused by the vitamin C deficiency. The fruit pulp has high level of vitamin C (~ 30 mg / 100 g pulp). Including it in daily diet would reduce the risk of Scurvy. It also boosts the immune system preventing any further possibility of viral or microbial infections.

Controlling diabetes – The presence of Feronia gum in pulp or leaves also helps manage diabetes by balancing the plasma glucose while preventing the spikes and plunges that often causes adverse situations for the diabetics.

Respiratory problems – The decoction made from leaves would help remove mucus providing comfort for chronic respiratory sufferers. It helps sore throat during cold, cough or fever by eliminating phlegm from the respiratory tract.

Reducing miscellaneous problems – 1) Purifying blood by removing toxins; 2) Boosting energy; 3) Beneficial to kidney for enhancing detoxifying ability; 4) Preventing malaria.

Nutrition: The fruit has good deal of nutritional values as per dietary concern. Approximately 100 g of fruit pulp has the following properties: The water content ~ 64 % and dietary fiber content is ~ 32 %, Protein ~ 2 % and fat ~ 0.5 %. As per mineral content, Ca ~ 85 mg, P ~ 32 mg, Fe ~ 1 mg, K ~ 600 mg, Cu ~ 0.2 mg. Concerning vitamins, Vitamin A ~ 55 µg, Vitamin B2 ~ 1.2 mg, Vitamin C ~ 30 mg, Thiamin ~ 130 µg, Riboflavin ~ 30 µg and β – carotene ~ 55 mg. The overall energy provided by one gram of fresh pulp is ~ 140 Kcal. Surprisingly, the fruit has high level of Potassium and β – carotene which may provide good heart health and immune boosting actions.

Phytochemicals and biological effects: Myriads of phytochemicals exist in fruit pulp, leaves, barks, seeds and roots of the Bel tree. All have the similar or several diverse medicinal role which are largely beneficial for the health. The leaves are often applied for treating fevers, abdominal pain, and palpitation of heart, urinary trouble dyspepsia, dysentery and vomiting.

Fruits, leaves and bark contain phenolics, carotenoids, alkaloids, pectin, tannins, coumarins, flavonoids and terpenoids. It also has many volatile compounds which fall in the category of terpenes and non-terpenes. A majority of them are,  Hexanal, isoamly acetate, limonene, β – phellandrene, p – cymene, acetoin, dehydro – p – cymene, linalool, 3,5 octadiene – 2 – one, α – cubebene, trans – p – Mentha – 2- 8-dieneol, citronellal, cineole, p – cymene, citronella, Citral, cuminaldehyde, β – cubebene, β – caryophyllene, hexadecane, Pulegone, α – humulene, verbenone, Carvone, carvyl acetate, dihydro-β – ionone, €- 6, 10, dimethyl-5,9-undecadien-2-one, β – ionone, psoralen, caryophyllene oxide, humulene oxide and hexadecanoic acid. The coumarin derivatives found are, aegeline, aegelenine, marmelin, O – methyl halfordinol and marmelosin. In addition the pulp has the others like, tartaric acid, linoleic acid, tannins, flavon-3-ols, leuco-anthocyanins, anthocyanins and flavonoids attached to the glycoside. The experiments verified that eating pulp in daily diet reduces the radiation induced sicknesses subsequently enhancing the patients’ survival. This radio-protective effect could be due to powerful free radical scavenging actions imparted by the flavonoids, β – carotene and other anti-oxidants within the pulp. A few of the phyto-compounds belonging to different categories in fruit pulp are shown below.

Pectin – In addition, the pulp of Bel fruit has large reservoir of polysaccharide (~ 38 % / 100 g wet pulp without seeds) mostly belonging to the pectin family. The unripe fruit possesses the most. Pectin, a natural polysaccharide is widely used in the food industry to prepare jams, jellies, lozenges and other confectioneries. It is frequently applied to the medicine to enhance the viscosity particularly for its demulcent effect. Inside intestine it increases the stool volume by swelling combating both constipation and diarrhea. It is used in making the commercially available antidiarrheal drug ‘Kaopectate’ by mixing with the kaolin (Al₂Si₂O₅ [OH]₄). Pectin is a polymer (M_w ~ 200) of D – Galactouronic acid. The molecular weight varies depending on its sources. As a bio-colloid it finds enormous applications as a food stabilizers or for the preparation of nanoparticles used for cosmetics and medicines. Pectin offers many beneficial actions primarily due to its physico-chemical nature. Being negatively charged (ζ = – 25 mv) polyelectrolyte for carrying large number of – CO₂H groups it can bind to number of cations. The polymer also contains – CONH₂ and – CO₂CH₃ intermittently in addition to the – CO₂H groups. For its huge array of negative charges, pectin acts as good detoxifying agent binding toxins and heavy metals. Further due to its good rheological or gel setting and high swelling nature, it is frequently used for the sustained release of various drugs that are doped inside. Its swelling index is high at physiological pH, 7.4 and also in the water. The combined effect of surface charge, rheological and emulsifying ability help exert strong anti-bacterial and antimicrobial role. Presumably, many believe that the fruit is consumed mainly for the medicinal reason. Additionally pectin exerts potent anticoagulant effect enhancing the blood coagulation time. The effect seems to be further potentiated for having coumarin derivatives which are known for their anticlotting behavior.

Obviously, biological and physiologic actions of Bel extracts occur due to the naturally synthesized chemical compounds within fruit, leaves or bark which have been recorded from the countless experiments. Bel has been studied thoroughly both in vivo and in vitro and its major components are isolated and identified including their pharmacological roles. Additionally, its ethnomedicinal use and effectivity have been verified for more than five millennia through various ways of consumption. These actions are mostly due to terpenes, flavonoids, carotenes, alkaloids and other bioactive components.

Terpenes – It is known that both fruit and leaves of Bel have number of terpenoids which induce strong physiologic effects. For example, Citral, a monoterpenoids produces potent anti-inflammatory actions via corticosterone independent pathway also simultaneously imposing antipyretic action. Whereas Limonene causes muscle relaxation also enhancing the sleeping time. Menthol triggers the TRPM8 receptor offering cooling sensation. Further, it blocks the Na⁺ channel preventing arrhythmia. Menthol can act also as an analgesic. It is a positive allosteric modulator of GABA_A receptor that enhances the GABA transmission inducing anesthetic effect. On the other hand, α – pinene, normally used in the aromatherapy lowers the heart rate and also acts as anti-inflammatory compound by suppressing the MAPK. Camphor activates TRPV3 channel causing warm sensation that also produces vasodilation, perspiration, heart rate increase and urination. It also has anti-inflammatory, local anesthetics and shows antimicrobial effect.  Besides having monoterpenoids, the fruit, leaves, berks and stems have several triterpenoids. The significant one is Lupeol which has versatile actions while acting as anti-protozoal, anti-microbial, anti-inflammatory, chemopreventive and anti-cancer / anti-tumor. It is a potent inhibitor of prostate and skin cancer. Its anti-inflammatory effect is via the reduction of IL- 4 production by T helper cells. The compound also acts as a male contraceptive by blocking the Ca⁺² channel action of sperm.

Terpenes

Flavonoids – The large level of flavonoids like Anthocyanins or Leucocyanins in leaves, fruit pulp and bark influence varieties of actions by scavenging the free radicals (ROS, NOS or super oxides, -O₂-) thereby preventing multiple damaging effects including lipid peroxidation which usually inflicts major cardiovascular problems. In that event, they also increase the activities of anti-oxidant enzymes like SOD, catalase or glutathione peroxidase. The incidences protect from number of chronic illnesses.

Flavonoids

Coumarins – Coumarins are also polyphenolic compounds of benzopyrone family having a phenol ring attached to the pyrone moiety. They are categorized either as benzo – α – pyrone or benzo – γ – pyrone. Both can exert physiologic actions. The pharmacological effects of coumarins practically depend on the substitution pattern. Records indicate that coumarin derivatives act as competitive inhibitor of vitamin K by depleting the Vitamin K molecule bound to enzyme, vitamin K epoxide reductase, thereby blocking the event of γ- carboxylation of glutamic acid residue linking to the clotting factor, Prothrombin. In that way it exerts its therapeutic potential as an anticlotting medicine. In addition to that anticlotting effect, it has other medicinal role like, fungicidal effect, anti-tumor effect and regulating the immune responses.  Many of them like Umbelliferone is used in the sunscreen. Psoralen is effective against psoriasis, eczema, vitiligo (loss of skin pigmentation) and lymphomas. Marmelide is a powerful antiviral drug effective against Coxsackiviruses (B1 – B6) IC₅₀ ~ 100 – 500 µg / ml. It is quite better than the antiviral compound Ribavirin. The compound is more efficient to work as antimicrobial and antifungal drug.

Coumarins

Alkaloids – Several alkaloids in Bel fruits, leaves or burks exert numerous beneficial role in health. For example, Skimmianine acts as selective 5HT₂ receptor antagonist. It is also an inhibitor of acetylcholinesterase enzyme that produces antiplasmodial action helping against malaria. The compound lowers the pulse rate by working on heart. Aegelin produces antihistamine effect working as H₁ receptor antagonist causing relaxation of tracheal muscle. Fragarine inhibits uterine action. It stimulates the adrenal gland releasing epinephrine thereby causing the relaxation of uterus.

Alkaloids

Miscellaneous components – Besides the above compounds the plant has innumerable beneficial compounds. One of them is Marmelin. It is a napthyl derivative. It induces apoptosis in various tumor cells especially very effective on colon cancer by activating TNF – α, TRADD and caspases. The compound and several of its derivatives are now commercially marketed for fighting against number of cancers. The other component found in significantly high level is β – carotene. It is a very common form of carotene, extremely lipophilic, synthesized within the plants. It is a precursor of Vitamin – A, also widely used as a food coloring agent.

Pharmacological effects of Aegle marmalos / Bel: Following are the major pharmacological role that have been already verified experimentally by using various ways of extracts (Ethanolic / Methanolic / other organic solvent / water) of different parts of Bel / Aegle marmalos eg, leaves, fruits, stems and berks. The most noteworthy fact is, none of the extracts produce any toxic effects either in animals or human.

Antidiarrheal action – The semi-ripe fruit reduces bacterial colonization in gut epithelium including production and action of any enterotoxins. It is the most reason behind its frequent use against infectious diarrhea which has been regularly practiced even today. The in vitro studies indicate its potential is very comparable to Ciprofloxacin and it is active against the strains of E Coli, Shigella spp and Vibrio Cholera. The presence of high level of Pectin offers further substantial assistance behind this anti-diarrheal action.

Anticancer action – The leaf and fruit extract shows strong anticancer effects. They are effective against vast number of cell lines like, leukemic K562, T-lymphoid Jurkat, B – lymphoid Raji, Erythro-leukemic HEL, melanoma Colo 38, and breast cancers MCF-7, MDA-MB-231 and most of the prostate cancers. Identifiable agents are Lupeol, Eugenol, Citral, Cineole and D-limonene. Lupeol exerts G1-S phase cell cycle arrest. Besides Lupeol others also has impact on cancer cells by various means, like decreasing cyclin D1, D2 and cdK2 expression while increasing the expression of p21; cyclin dependent kinase inhibitor involved in controls the overall event.  In addition to those compounds, Marmelin in fruit potently inhibits large section of epithelial cancer cells like, colon – HCT116, liver -Hep – 2 and alveolar carcinomas, human melanomas, pancreatic adeno carcinomas etc. Marmelin causes G1 cell cycle arrest inducing apoptosis in the tumor. Interestingly, it has no effect on any normal cells. Taking for granted, every section of Bel tree is enormously beneficial which has been already pointed out by the ancient Ayurveda.

Antiviral and antimicrobial effect – The extracts of leaf or fruit have powerful antifungal effect on animal and human fungi. The extract interferes with the Ca⁺² di-picolinate metabolism pathway that would certainly inhibit the spore germination process. Ca⁺² uptake and its subsequent utilization is usually the prime event determining whether it would germinate or stay dormant. The extract lowers the vegetative fungal body inside the host and in solid medium. The possible active compound identified is Marmelide (IC₅₀ ~ 62.5 µg / ml) which exists in the leaves, stem, bark and fruits with varying levels. The efficiency (IC₅₀) to inhibit Coxsackie viruses B1 – B6 is; leaves ~ 1000, stem ~ 500, bark ~ 1000, fruit ~ 250 µg / ml.

Antipyretic effect – The antipyretic effect of extracts are almost comparable to Tylenol / Paracetamol (100 mg / Kg body weight) which has been proven by the animal experiments.

Anti-inflammatory and anti-allergic effect – Extracts play anti-inflammatory role in the case of acute and subacute inflammatory conditions. Under the circumstances, leaf and fruit extracts show much dominance compared to the other parts. The identifiable agents are Lupeol and Skimmianine. Additionally, presence of Aegelin in the extracts exerts powerful antihistaminic effect by blocking the H₁ receptor actions thereby protecting from any allergic and asthmatic manifestation.

Anti-fertility effect – As a folk medicine in the villages of India, leaf extract is often used to engender the anti-fertility actions. It is also identified that extract from any parts of the Bel tree provides good reversible male contraceptive effect. In that regard the bark extract is more pronounced. The compounds Marmin and Fragarine are recognized to be the active agents since both can individually reduce the male fertility. The animal experiments indicate that methanolic extract of bark reduces sperm density, motility, viability, and acrosome integrity. Exfoliation of elongated spermatids, nuclear chromatin condensation and degeneration are found within the testes. Finally time dependent complete infertility could be achieved. But importantly, the effect could be fully reversed after the withdrawal of treatment. So the extract appears to be an excellent male contraceptive which is used as per need.

Radio-protective actions – The effect of radiotherapy during the cancer cure often damages bordering tissues that inflicts cytotoxicity. The use of radio-protective agents, at this condition, is necessary to prevent that undesirable effect. Animal experiments show that the extracts of various parts of Bel plant have a potent preventive role, particularly the leaf extract, which is noticed to be superior to the normally used 2- Mercapto-propionyl -glycine. Experiments further indicate that Bel extracts reduce radiation induced DNA damage in peripheral blood lymphocytes and bone marrow cells within human and animals. The effect is caused by its scavenging ability of free radicals generated by the radiation.

Chemopreventive action – Experiments have proven that chemoprevention leads to the cancer prevention. Studies on animals show that the Bel fruit extract exerts chemopreventive role against numerous carcinogenesis. The presence of phytochemicals like Lupeol, Eugenol, Limonene, Citral, and anthocyanins are responsible for this act.

Diuretic action – The fruit extract exerts diuretic action as measured by the urinary volume and its Na content. The ethanolic extract (500 mg / Kg) produces more significant effect by excreting Na within experimental animals.

Antiulcerative effect – The aqueous and ethanolic extracts of seeds and fruit pulp show good anti-ulcer effect in various animal models. The effect is generated due to its large flavonoid content, particularly Quercitin that enhances the anti-oxidant enzymes assisting the anti-oxidant behavior.

There are far more pharmacological role played by the extracts from fruits, barks and stem or any other parts of the Bel tree which could be seen less significant because of their low levels. But considering the possibility of cumulative effects, adding the delicious fruit pulp alone in the daily diet would definitely help maintaining a good health. It is the basic reason why the tree has been revered historically for more than five millennia and even today. It has ample of things to offer regarding our health.

Chicory

General features: Chicory, botanically named Chicorium Intybus is a perennial herbaceous plant like Dandelion which belongs to the Asteraceae family. Chicory originates from the Mediterranean regions and produces bright blue flowers although occasionally they are seen in white or pinkish color also. Varieties of Chicory plant have been identified. All of them are consumed either for the salads or for coffee or as a spice to add in cooking. The fresh green leaves are used in salads whereas dry, baked and grinded matured roots are employed as a coffee substitute or frequently mixed with the roasted coffee to provide tasty flavor to the drink. Currently it is cultivated mainly for those purposes. Chicory is actually a wild plant grown on roadside commonly eaten up by the cattle or livestock. It is also considered as forage crop. The plant carries several names like, blue weed, blue daisy, coffee weed, wild endive and others. Chicory has tough and less hairy stem. It is ~ 40 inches tall. The leaves are trailed, lanceolate and without lobes. The flower heads are ~ ½ inch wide and bloom between July and October. In some places like in Europe, India, South Africa, New Orleans (USA) and Mediterranean regions, as a traditional practice Chicory roots are often used as coffee substitute. The roots are loaded with Inulin, a polysaccharide closely analogous to starch. Inulin is found within the roots of Asteraceae family members. It acts as carbohydrate storage in Artichoke, Yacon and Dahlia. Inulin level in those roots varies 20 – 70 % of the total carbohydrate content. Aside being used in coffee, Chicory roots are also used in making beer accompanied with hops providing different flavors. The use of Chicory is gaining more attention in recent days as a dietary supplement or soluble fiber especially filling the yogurt to work as prebiotic. The fresh root contains ~ 70 % Inulin, 15 % sucrose, 5 % cellulose, 6 % protein, 4 % ash and 3 % other ingredients whereas the dry roots contain  > 80 % . The root tastes bitter for the existence of sesquiterpene lactones (Lactucin and Lactucopicrin), coumarin derivatives and glycosides.

History of Chicory: ‘Chicory’ is originated from the Egyptian word ‘Ctchorium’ meaning wild plant. Interestingly even considering being wild, the plant was eventually cultivated for the sake of animal feed and later came into human use as well around 5000 years ago according to the ancient Egyptian agricultural history. It was regarded as a medicinal plant which was mentioned at the then time by the legendary botanists, medicinal giants and intellectuals like, Galen, Ovid, Horace, Pliny (elder) and Virgil. Galen named the plant ‘friend of the liver’ for its stimulating role on that organ. In early days, its use as a vegetable in salad was commonly practiced among the Greeks, Romans and Egyptians. The plant was also used afterward as animal fodder around 17^th century in the Europe. The root was introduced as human food only in the case of dire situation. It is very bitter and woody by the taste. Later in Belgium and surroundings, the young tender roots were consumed as a human food and that practice still continues even today. The use of roasted roots of matured plant substituting coffee is suspected to be initiated during the Napoleonic war in 1808 when Continental Naval Blockade was established by Napoleon himself. Although some reported that the use of Chicory as additive in coffee was already started around 1785 in Holland. Napoleon’s blockade deprived the entire Europe including France from the actual coffee. At that time the French coffee makers learnt the dried Chicory roots being an appropriate substitute. The dried and baked roots provide good flavor that attracts and satisfies the coffee drinkers’ tastes. That practice is continuing still today, even far after the Napoleonic era. At the end of Napoleon’s naval blockade, the use of Chicory root lessened but not fully diminished. By that time, it found its way into many French colonies. So millions of pounds of Chicory roots started of being exported to many parts of the world. Louisiana in the US was one of them. It has been recorded that the use of baked matured chicory root in coffee as additive was genuinely practiced also in several places of the North America. But the event openly came into the public knowledge during the American Civil War. Similar blockade was imposed by the Union Navy that created a severe shortage of coffee in Louisiana. Due to large French influence in Louisiana, many of the New Orleanians was already familiar with the use of Chicory root. Its use was immensely soared so was the cultivation. The use as additive in coffee still continues even in present days. New Orleanians still hold that practice with retribution even with abundance of coffee. The café au lait is still made in New Orleans with thick rich black coffee plus baked chicory root and boiled milk just like that made in the days of naval blockade during American Civil War.

Medicinal components and pharmacological role: The medicinal values of Chicory have been identified over a five millennia. The recorded beneficial actions are matched with the recent day’s findings. Around 19^th century Europe, the French chefs and intellectuals thought that Chicory’s action is contrary to the effects of caffeine in coffee. They also suggested that persons having bloodlessness and lymphatic problems should avoid its use. The early report also claimed that the decoction made by boiling dry roots with water help pulmonary congestion and also effective against Jaundice and liver enlargement. Chicory syrup was prescribed as a laxative especially for the children. The ancient herbalists also thought that it can increase the bile production, bile flow (Cyanarine acting as Cholagogue and choleretic), moderately lower the heart rate, reduce blood cholesterol and kill bacteria / parasite inside the intestine. All these past findings are almost identical to the current ones. The recent studies in animal show that Chicory lowers the plasma cholesterol and increases the HDL / LDL ratio. The oil from Chicory roots is effective in eliminating the intestinal parasites and worms in human and grazing animals. The anti-parasite monoterpene materials (1, 8 – Cineole, Camphor, Myrtenol and Thujone) accumulate in the roots which is common to the plants of that genus. Thujone is toxic to herbivores therefore it defends the plants from their attack. Despite their presence, Chicory shows no hepato-toxicity, to the contrary it offers hepato-protection against it. The plant is a folk medicine in Germany and other European nations. It is used to treat gallstones, gastroenteritis and sinus problems. Its poultice is frequently applied during any cuts and bruises for its anti-inflammatory effect (Chamazulene, Axillarin). The high level of Inulin helps losing weight, constipation and improve intestinal functions. It also enhances the bone density by increasing Calcium and other mineral absorption through intestine. In addition to its anti-parasite role, Chicory has antiviral and anti-inflammatory effect due to Axillarin, Cyanarine and Chamazulene which are also found in Tansy. There are few sesquiterpenes and coumarin derivatives which is perhaps the cause behind its bitterness. The sesquiterpenes are mainly Lactucin and Lactucopicrin. Lactucin has analgesic and sedative effect. In addition, it has anti-malarial effect. The compound acts as adenosine receptor agonist lowers tachycardia which is opposite to the effect of caffeine. The Coumarin derivatives have significant medicinal effect. They are widely known for its anti-coagulant action behaving as vitamin – K antagonist. In Chicory the predominant ones are Aesculetin, Aesculin and Umbelliferone. Aesculetin is a powerful anticoagulant and interacts with Warfarin. So one should be cautious about the use of Chicory. Aesculin acts as a vaso-protective agent. Umbelliferone, besides being anticoagulant is used in sunscreen for strong UV absorption around 300 – 325 nm.

Medicinal benefits:  Both leaves and roots of Chicory plant offer number of beneficial effects. Besides eating in salads, crushed leaves are used as poultice to reduce swelling and inflammation of the skin. Since most organic components are accumulated inside the roots so, it exerts the major effects. It is used to stop upset stomach or diarrhea, constipation and gall bladder problems. Its role on cancer is never fully established although some claim the capability. It is certainly effective in reducing the tachycardia and also increasing urine production. Following are few major beneficial effects exerted by the Chicory:

Hypertension and high heart rate – Lactucin produced in Chicory possibly lowers tachycardia / arrhythmia and arterial pressure with additional assistance from high Potassium content (450 mg / 100 g root). The root also has good amount of Magnesium (30 mg / 100 g root) which helps further dilating the blood vessels thereby reducing hypertension. It is believed that Inulin perhaps provides helping task in this event.

Arthritis & Rheumatic diseases – Chicory helps absorb various minerals in body enabling to enhance the diuretic actions which in turn facilitates the drainage of uric acid thus lowering the risk of gout and other rheumatic problems often created by the hyperuricemia.

Stress, anxiety and muscle cramps – In addition to other chemical ingredients, high Magnesium level is able to reduce the stress, anxiety, spasmophillia and even depression.

Alzheimer’s and neurological disease – The presence of Lactucopicrin in Chicory is an inhibitor of Acetylcholinesterase. So blocking it would impact on neurological disorders particularly on any cognitive impairment or difficulty in REM sleep disorders or dementia.

Diabetes – Studies show that consuming Fructo-oligosaccharides / Inulin in daily diet can reduce plasma glucose level among the diabetic sufferers.

Dyspepsia, Digestion and body weight – Chicory extract acts as a gastric tonic stimulating gastric juice production facilitating the overall digestive process. Further it is considered to be a prebiotic due to having soluble dietary fiber like Inulin and Fructo-oligosaccharide. These components help grow beneficial bacterial strains helpful for colon and simultaneously advantageous to the host. Frequent use of Chicory improves digestive ability subsequently help maintain the gut flora. It acts against constipation. They can also control the body weight perhaps due to the presence of soluble dietary fibers, since proper digestion is largely a factor behind the weight-loss diets.

Bile production – Decoction made from the roots of Chicory have strong choleretic properties. Cyanarine enhances the production and secretion of bile enabling to digest the fatty foods inside intestine.

Insomnia – The existence of Lactucopicrin and Lactucin impose analgesic and sedative effects on CNS along with anxiolytic effect.

Menstruation – Decoction of Chicory root helps regularize the irregular menstruation for women. Although some people claim that Chicory can induce unscheduled menstruation. Chicory stimulates uterus inducing contraction which seems initiate the menstruation periods. In this way, it also acts as abortifacient therefore unsuitable for any pregnant women. Further it should be avoided by the nursing mothers.

Side effects:  Occasional contact dermatitis occurs for few personnels when coming in contact with Chicory leaves. Chicory can lower the rate of drug metabolism for several β – blockers and analgesics due to its effect on Cytochrome P-450 in the liver. Due to the large presence of coumarin derivatives, people using anti-clotting medications should be careful of drinking Chicory.

 

 

Coffee

General features: The plant is a shrub belonging to the genus, Coffea producing berries that on drying, grinding and brewing provides drinkable coffee. Coffee plant grows in tropical and subtropical climate of Africa, Southeast Asia and Latin American nations. Two major species are usually cultivated for the commercial reasons, one is Robusta / Coffee Canephora whereas the other is called, Coffee Arabica. The later variety is considered to be a precious and popular commodity which is the native of Ethiopia, South East Sudan and Northern Kenya. Coffee Canephora / Robusta originates from the Sub-Saharan Africa, Guinea, Uganda and Southern Sudan. There are other less popular species like C. Liberia, C. Stenophylla, C. Mauritiana and C. Racemosa. About ¾ of worldwide cultivation is C. Arabica. But Robusta / C. Canephora contains ~ 50 % more caffeine than the C. Arabica. Robusta is usually used in making Italian Espresso offering strong full-bodied taste with foamy head. Approximate worldwide production of coffee ranges from 8 – 9 million metric tons in a year. Among them Brazil produces the highest load (2.8 – 3.0 million tons) and Uganda the least (0.2 million tons). Next to Brazil is the Vietnam which grows 1.4 million tons and India stands 7^th producing 0.3 million tons of C. Arabica. Columbia produces ~ 1.0 million tons placing itself next to the Vietnam. The plant belongs to the Rubiaceae family. It is evergreen shrub that grows nearly ~ 15 ft in height producing glossy dark green leaves, 4 – 6 inches long and 2.5 inches wide. It bears white flowers growing in clusters spreading sweet fragrance of jasmine. Berries grow following the arrival of flowers. They are green when immature but turns red / crimson on ripe. Majority berries have two seeds although some variety (~ 10 %) bear just one. In most cases, it takes 9 – 11 months to ripe the berries. The ripen seeds are processed, dried and stored for use as coffee beans which are grinded at home and brewed for making the fresh pots of coffee.

History: The coffee plant was first discovered in Ethiopia around 11^th century. It was called ‘Magical fruit’. The legend says that coffee was actually discovered by the Ethiopian goat herder, called Kaldi. They noticed that their goats become energized and dance around for much longer time if they consume those red berries or its leaves. Thus being curious, they started using it and in due course experienced the similar effect. It was later thought that the concoction made by boiling the fruits with water might have some medicinal role. Eventually along with the time, drinking of coffee came into practice as a social norm. The evidences of habitual coffee drinking was historically noted around 15^th centuries within the Sufi monasteries of Yemen. At that time coffee was exported from the Ethiopia to Yemen. In fact they initially started the coffee cultivation. The Sufis used the drink to put more attention and energy during their prayers. They believed that it adds a kind of intoxication while chanting the name of God also provides extra alertness throughout the night time prayers. Historians traced back the practice of coffee drinking which seems spread afterward all over the recent days Middle Eastern nations (Mecca & Medina, Damascus, Baghdad), North Africa (Cairo, Alexandria) and also Constantinople in Turkey and Europe. Around16^th century, loads of coffee houses were built in the cities especially within the campuses of universities thus making the coffee drinking a socially accepted custom among the common people, particularly within the scholars. It was highly associated with the Sufism. Almost at the same time it suffered deliberate prohibition by the orthodox imams of Mecca for its stimulatory role. But the verdict was overturned by the order of Ottoman Turk Sultan, Suleiman I in cooperation with the Grand Mufti of Constantinople who issued a Fatwa allowing pursue the drinking of coffee.  So around that century, coffee drinking gained further spreading in more Middle East countries and later to the Southern India, Persia and more places in Africa. Afterward it finds the way to move toward the Balkan States, Italy and rest of the Europe, American continent and Southeast Asia. History said that in 1727, the King of Portugal sent Francisco de Melo to French Guiana for collecting the coffee seeds. He succeeded in that job by mesmerizing French Governor’s wife through his physical charm and wonderful conversation. Later she sent enough amount to initiate the coffee industry of Brazil. After gaining independence in 1822 from the Portugal, Brazilian coffee industry soared astonishingly high. Unfortunately, huge loads of rainforest were struck down near Rio and Sao Paulo for its plantation. Thus with time, the drinking of fresh brewed coffee turns enormously popular all over the continental America especially in the US after the incidence of Boston Tea Party at the Boston harbor in 1773. In India, coffee arrived way before the arrival of East India Company through the Sufi saints of Yemen. One of them is Baba Budan who established a temple on the hill of Chikmagalur district of present Karnataka state and started the coffee plantation at that region. The entire hill tracts of Sothern India is seen as a prime region of coffee cultivation. Karnataka grows 53 %, Kerala 28 % and Tamil Nadu 11 % of India’s total coffee production. Besides the southern states, Northeastern seven-sister states (Assam, Manipur, Meghalaya, Mizoram, Tripura, Nagaland, and Arunachal) also grow considerable amount of coffee. Two major varieties are usually produced in India, Arabica and Robusta. Indian coffee is famously regarded for intense flavor and aroma, much superior to its Pacific and other counterparts. Among the Indian variety, Arabica is grown being the highest. Nearly 80 % of production is exported to the Europe and US, of which 29 % reaches to the Italy. As per quality, the product from Babu Budan Giri hills of Chikmagalur stands up as the best. Way afterward, the major European control on coffee plantation and trade in Southeast Asia and the world came into effect by the involvement of Dutch East India Company although initially, it was dominated by the French dealers. The Dutch East India Company instructed the then Governor of Batavia to initiate the coffee plantation and later its export to the Europe. Ultimately, the effort turned as a huge success and around 1719, there appeared a brand named variety, “Java coffee”. The success energized them to further initiate the coffee plantation in Ceylon and Indonesian islands. In that trade, they started joint maneuvering with the French conglomerates particularly allying with the largest coffee trading company, Jardin des Plantes of Paris.

Chemical processes involved in coffee production and associated biologic effects: The chemical contents of coffee expectedly varies according to the species and ways of processing them. In addition, the climatic conditions, soils and fertilizers also add a good deal of differences that also dictates the quality, taste and flavor of the drink. But qualitatively irrespective of the species differences all varieties possess almost the similar ingredients, water, carbohydrates, fibers, proteins, free amino acids, lipids, minerals, organic acids, Chlorogenic acids, Trigonelline and caffeine. Besides those common items, minor phenolic compounds like anthocyanins and lignans and diterpenes are identified mainly in the Green coffee. The table below would provide an idea regarding the species differences and processing methods and the chemical contents. The data is intended for C. Arabica and C. Robusta which are the two major kinds produced and sold around the globe. The changes occur would also be discussed further especially regarding the technical processes performed on making green coffee seeds while producing the beverage. The major processes that are involved in coffee productions are, 1) Green coffee production, 2) Roasted coffee production and 3) Decaffeinated coffee production.

Chemical composition, mass percent of dry matter

Component	Arabica Green (%)	Robusta Green (%)	Arabica Roasted (%)	Robusta Roasted (%)	Arabica Instant (%)	Robusta Instant (%)
Caffeine	1.3	2.3	1.2	2.4	2.5	3.8
Trigonelline	0.8	0.7	0.3	0.3	0.7	0.4
Carbohydrate	53.7	50.7	38	42	46.6	44.7
Chlorogenic acids	8.1	9.9	2.5	3.8	2.6	1.6
Lipids	15.2	9.4	17.0	11.0	0.11	0.26
Amino acids	11.1	11.8	7.5	7.5	6.2	6.0
Organic acids	2.3	1.7	2.4	2.6	8.1	7.9
Melanoidins	——-	—–	25.4	25.9	25.1	28.6
Volatile aroma	Insignificant	Insignificant	0.1	0.1	nil	nil
Minerals	3.9	4.4	4.5	4.7	8.0	7.4

Green coffee production – In case of green coffee production, the beans are kept unroasted before subjecting to any further processing steps. It is noteworthy that irrespective of the process of roasting, its caffeine contents remain unchanged whereas the levels of chlorogenic acid undergoes significant alterations. Roasting considerably reduces the level. The compound is thought have a strong beneficial role on health. During the production of green coffee, at first, after the good fruit selection two different strategies are followed during pulp extraction that often determines the coffee quality. One is dry and the other is wet method. In course of dry method, the berries are exposed to the sun and dried either in the open air or using an air dryer or both in order to reduce the moisture content ~ 10 – 12 %. The seeds are then husked to remove the dry skins and other layers from its surface. The dry beans are then sorted and packaged for shipment and is ready to be brewed. Whereas the wet process considered being sophisticated, produces better quality brew. The skin and flesh are removed from the berries by pressing. The remaining flesh contents are removed by fermentation while soaking in water and adding microbes to remove any extra mucilage by breaking down celluloses from surface of the coffee seeds. The seeds are thoroughly washed by scrubbing in the machine to remove the leftovers, silver skin and parchment. Later the seeds are dried in the sun or by any controlled mechanism while keeping the moisture content about 10 – 12 %.

Roasted coffee production – The coffee aroma rests on its way of roasting the seeds. Although apparently it seems simple but the underlying chemistry is highly complex and not yet fully understood. The high roasting temperature brings numerous changes within the seeds both physically as well as chemically. The roasting temperature usually varies from 210^o C to 240^o C. At the initial phase of roasting free water evaporates. At 130^o C the existing sucrose within seeds caramelizes turning to brown appearance with simultaneous swelling of the seeds. At 160^o C a series of chemical reactions occur making the seeds to be light brown with considerable increase of the seed volume. The chemical reactions that triggers around 190^o C are genuinely responsible for creating aroma and flavor of the coffee owing to the initiation of Mailard and Strecker reactions caused by the interactions between reducing sugars, proteins and others producing various high and low molecular weight compounds like Melanoidins (Mailard reaction product, MRP) which are degraded and produced simultaneously. Below is the scheme for Melanoidins’ production from the aldose sugar. Melanoidins are heterogeneous nitrogen containing brown colored pigments produced by the Mailard reaction providing color to the coffee, cocoa, bread, malt and honey. The reaction occurs between carbonyl group (= C = O) of reducing sugars and the amino groups (- NH₂) of amino acids from peptides and proteins. This is a non-enzymatic way of browning reactions which normally takes place in course of many food preparations. It was discovered in 1912 and since then widely applied to develop color, aroma and flavor in the foods. The reaction products are immensely complex creating numerous compounds of varying molecular weight depending on the nature of food products. The chemical characterization of Melanoidins and its health effects are now an attractive subject of study. Most of the Melanoidins are negatively charged especially those having low molecular weight (~ 5.0 KDa) within the coffee which is suggested to be due to the presence of Chlorogenic acid. But aside from its existence, it has been proven that whenever any types of Melanoidins are formed, they acquire negative charge having the PI ranging between pH 3.5 to 4.85. Thus, whichever would be the situation, the acidity of brewed coffee mostly seen laying around pH ~ 4.5.

Suggested carbohydrate based Melanoidins’ structure [R = H, Glc or (Glc)_n]

Strecker reaction is an old way of synthesizing α – aminonitrile which is ultimately converted to α – amino acids. It is basically condensation reaction between aldehydes / ketones with primary or secondary amines or even with the NH₃ to produce Schiff bases / imine. It is then react with the CN^– anion generating α – aminonitrile which subsequently hydrolyzes to α – amino acids. The original Strecker reaction produces racemic mixture of enantiomeric forms of amino acids. But chemists afterward developed enantioselective method of reactions that uses catalyst for making particular enantiomer.

The pathways of Mailard reaction producing high and low molecular weight Mailard reaction product

Coffee roasted at higher temperature for shorter time often exhibits higher acidity, more soluble matters and different chemical profile than the same staff roasted at low temperature for a longer time.

Schematic representation of Strecker reaction

The reactions are interrupted at desired points for preferred color or aroma providing light to high degree of dark color according to the individual’s choice.

Decaffeinated coffee production – The process of decaffeination is conducted prior to the subjecting for roasting. Normally the process of solvent extraction is applied using di-chloromethane or ethyl-acetate. The process uses green seeds for the removal of caffeine. It is by far the least costly method of decaffeination. Along with caffeine many other substances are also removed which usually detoriate the flavor and taste as well. The extracted caffeine finds its market in making other beverages. After the extraction process, seeds are thoroughly washed and dried bringing to the level of original moisture content. The major concern regarding solvent extraction is the residual solvent sticking to the coffee beans. For its further removal, any residual solvent sticking to the surface is evaporated off from the extracted seeds by subjecting to 70^o C. Additionally, the roasting temperature is also high enough to remove it completely. In recent days owing to health concern, in the US and some other nations, only water or supercritical CO₂ holding at super high pressure ~ 200 atm at 31^o C are applied for the sake of decaffeination. The process maintains the taste, flavor and aroma in a much better way.

Instant coffee production – Basically, the process involves extraction of soluble matters from the ground coffee using hot water under high pressure. The extracted materials will be cooled and if necessary would be occasionally centrifuged to remove any particulate matter. The liquid is then concentrated and freeze dried keeping the moisture content ~ 5 %. Some manufacturers use spray drying using high temperature and high pressure to volatilize the water and subsequently hot air would dehydrate bringing the soluble matter to powdered form. But freeze drying offer better taste and aroma compared to its spray drying counterparts.

Caffeine – It is the most widely used debatable ingredient used in the beverages. The compound is heat stable achiral alkaloid chemically defined as methyl xanthine providing bitter taste that constitutes ~ 10 % of the perceived bitterness of coffee. The half-life (t_1/2) of caffeine in an average adult is approximately 4 – 7 hours depending on the body weight. The smoking often decreases t_1/2 about ~ 30 % whereas use of oral contraceptives causes the doubling. Pregnancy enhances the effect far more, increasing t_1/2 to greater than 20 hrs. So caffeine consumption during pregnancy needs to be cut down to a considerable extent.  The compound is moderately soluble in water but shows enhanced solubility in organic solvents thus recognized being a lipid soluble component, enabling to cross the blood brain barrier. The level of caffeine is almost double in Robusta than in the Arabica species. The Canadian study emphasizes that average intake of caffeine per day for an adult person should not be more than 2.5 mg / Kg of the body weight. Caffeine is labeled as addictive material so over-consumption should be avoided since that often exerts transitory health problems. The compound has immense biological as well as physiological role inducing both positive and negative effects. It prevents breathing disorders, broncho-pulmonary dysplasia in premature babies. It helps cerebral palsy affected persons supporting for cognitive functioning. It is used as a treatment for orthostatic hypotension (falling of blood pressure during sudden stand up or rise. Systolic drops ~ 20 mm and diastolic ~ 10 mm Hg. It occurs due to the delaying of constriction of lower body blood vessels.). Caffeine modestly helps the case of Parkinson’s sufferers. Acting as a nervous system stimulant it lowers drowsiness and fatigues, improves motor coordination, wakefulness, concentration and improve the reaction time. It delays sleep but can improve task performances during sleep deprived state. In that way fewer mistakes occur in the case of caffeine users during night shift. Besides coffee plant caffeine has been identified in seeds and nuts of various plants of South America and South East Asia. The compound helps protect against the predator insects also prevents germination of any nearby seeds.

It stimulates the central nervous system by working as adenosine receptor (A₁– K_D = 12 µM; A_2A – K_D = 2.4 µM; A_2B – K_D = 13 µM; & A₃ – K_D = 80 µM) antagonist because of its uncanny structural similarity with the adenine. Adenosine is an inhibitory component on CNS so by blocking its action caffeine helps the stimulatory behavior. Antagonism by caffeine stimulates medullary vagal nerve, vasomotor and respiratory center as well thus increasing the respiratory rate with simultaneous constriction of the blood vessels. Antagonism also helps various other neurotransmitter release including acetylcholine. Antagonism of A₁ receptor exerts heart palpitation. Interaction between caffeine and A₂ receptor causes wakefulness also enhances the arousal. Further, besides acting on adenosine receptors, caffeine functions as Inositol triphosphate receptor (IP3₁) antagonist. It also directly activates voltage independent Raynodine receptors -1, 2 & 3. As per further antagonism, it efficiently blocks the ionotropic Glycine receptor. Caffeine modulates the actions of dopamine receptors although it does not bind directly but it enables to release dopamine within several parts of the brain. The chronic use of caffeine inhibits eventually prevents that dopamine release. Like the xanthine analogs, it is a competitive as well as nonselective inhibitor of all phosphodiesterase that enhances the accumulation of cAMP causing the activation of PKA enzyme which in turn prevents TNF – α, Leukotriene synthesis leading to the lowering of inflammation and innate immunity. It also inhibits acetylcholine esterase thereby raising the level of acetylcholine which might have beneficial effects on several neurological disorders like in the Alzheimers. Caffeine is metabolized mostly in the liver by cytochrome P450 enzymes into mainly paraxanthine (~ 80 %), theobromine (14 %) and theophylline (~ 6 %). But traces amount of 1, 3, 7 trimethyl uric acid is also identified. Interestingly, those metabolites are also further metabolized. Persons with severe liver disease accumulate caffeine in the liver increasing the clearing rate or t_1/2 life. Paraxanthine increases lipolysis thereby elevating glycerol and fatty acids in the circulation. Theobromine, a major alkaloid found in the cocoa bean / chocolate dilates blood vessel and also increases the urine volume. Theophylline relaxes smooth muscle in bronchi therefore commonly used to treat asthma but the therapeutic doses are much higher and in no way attainable by metabolizing action of the liver. Acute consumption of caffeine produces negative effects on glucose tolerance, glucose disposal, insulin sensitivity in lean, obese and type 2 diabetic patients. High caffeine intake also causes urinary excretion of minerals particularly calcium. Caffeine overdose creates number of serious problems like nervousness, irritability, insomnia, restlessness and palpitations. Caffeine dependency (~ 1.5 gm / day) is usually the major cause of overdose which is recommended to avoid.

Caffeine metabolism in liver

Trigonelline –  

 

The compound is an alkaloid produced by the methylation of nicotinic acid (vitamin B₃) within the coffee beans. It adds extra bitterness to the coffee. The variety, C. Arabica contains more of this alkaloid than Robusta / C. Canephora.  Physiologically, it prevents invasiveness of several cancers and helps grow dendrites and axons within the animals signifying its possible positive role in memory improvement. According to the recent studies, Trigonelline can behave also as a phytoestrogen. Further, its demethylation during the roasting process of coffee beans produces nicotinic acid which is considered to be an important vitamin, B₃. The compound is mostly metabolized in the liver and excreted via urine.

Chlorogenic acid – It is a phenolic component primarily formed by the esterification of trans – cinnamic acid analogs (Caffeic, Ferulic, p – Coumaric) with (-) Quinic acid. Those compounds add astringency, bitterness as well as acidity to the brew. It is one of the causes behind undesirable flavor of brewed green coffee. The production of phenol and catechol from hydrolysis adds additional unsavory flavor. The level of chlorogenic acids in Robusta / C. Canephora is about twice the higher than C. Arabica. Numerous studies concerning the intake of coffee and health effects indicate that aside from caffeine the existing other components enable to exert various beneficial actions like lowering the risk of type2 diabetes, Parkinson and Alzheimer diseases and cancers especially in the liver. These helpful role is possibly attributed due to the strong antioxidant actions of Chlorogenic acid and its analogs. Studies conducted in the US, Demark, Brazil, Japan and many Mediterranean nations indicate that coffee is the largest antioxidant contributor in daily diet. The epidemiological surveys associated with the coffee intake and antimutagenic activity indicate a positive role, presumably due to the chlorogenic acids and its metabolites which involves free radical scavenging, heavy metal chelation, inactivation of various endogenous reactive compounds. Several analogs provide antiviral actions toward adenovirus and herpes also display hepatoprotection against bacterial and virus actions or injury. The compounds are seen to inhibit HIV-1 replication in cells which indicates genuine possibility to synthesize coffee based anti HIV drugs.

Cafestol & Kahweol –

These are pentacyclic di-terpenes, identified mainly in the Robusta variety. They normally exist as salts or esters of fatty acids (~ 20 %) within the lipid fraction in coffee. They are also found in coffee oil. The total di-terpene content is noticed to be higher in the C. Arabica than C. Robusta.  These terpenes also have anti-carcinogenic and hepatoprotective properties. Whereas contrarily, its higher consumption is seen to be associated with the elevated homo-cysteine and LDL level in plasma which is indirectly associated with the risk of cardio-vascular diseases. Interestingly, its level is seen higher in the unfiltered coffee because of its poor solubility therefore might be trapped by the paper filter.

Lipids – This is perhaps the major content in coffee which is almost twice higher within C. Arabica (14 g / 100g dry matter) than C. Robusta in both green and roasted varieties whereas the instant category lacks it appreciably. The lipid fraction is composed of tri-acyl glycerol (75%), free fatty acids (~ 1%), sterols (~ 2% unesterified and ~ 3% esterified), tocopherols (~0.1%) and di-terpenes. Most of the fatty acids in coffee are unsaturated like Linoleic (~ 54%), Oleic (~14%) and Linolenic (~ 3%). Fatty acids are important for health besides, they maintain the integrity of freshness in coffee avoiding staleness caused by hydrolysis and oxidation of tri-acyl glycerol. Concerning the sterol content, Sitosterol is 54 % and stigmasterol and Campesterol together is 40 % presenting equal proportions. The level of tocopherols in coffee is ~12 mg / 100 g in green variety. All isomers (α -, β – and γ -) of tocopherol exist in all varieties of coffee but with a varying degree but out of them β – tocopherol shows at the highest level followed by α and γ isomer. The major existence of tocopherol has been identified in the oil fraction which shows ~ 5 mg / 100g of green coffee. Tocopherols are widely known for vitamin – E actions. They are also fat soluble powerful antioxidants.

Soluble dietary fiber and carbohydrate – Soluble dietary fibers are normally high molecular weight polysaccharides affecting to raise the viscosity of brewed coffee. The most notables are galactomannans and arabinogalactans type – 2. The type – 2 arabinogalactans are seen highly branched in brewed green coffee. By nature, these polysaccharides are highly complex and covalently linked to the proteins of which ~ 10 % amino acid residues are 4 – hydroxy proline. Besides arabinose and galactose there exists raminose and glucuronic acids also. Recent interests are focused particularly on various soluble dietary fibers since because they are indigestible for humans therefore enable to reach the colon intact thus serving as substrates for beneficial colonic microbiota fermentation. The event affects number of metabolic process in many ways like lowering of plasma cholesterol, modulating blood glucose and insulin responses. Fermentable polysaccharides undergo degradation by the microbiota inside colon producing short chain fatty acids lowering the colonic pH impeding the growth of pathogenic species and other beneficial lactic acid bacteria. Regarding carbohydrates, they are ~ 50 % of the dry weight of any coffee and composed of poly-, oligo-, di- and monosaccharaides. Sucrose is important for the quality and flavor. Simple monosaccharides also exist as fructose, glucose, mannose, arabinose and rhamnose. The carbohydrates are essential for Maillard reactions and caramelization that helps develop the color and aroma. Higher sucrose content offers superior aroma and flavor which is seen higher in C. Arabica. Polysaccharides with high molecular weight gives good body to the brew. It has been identified that soluble dietary fibers especially the cellulose exist in considerable amount in the brew which has significant bioactive role in intestine / colon.

Proteins / peptides and minerals – In a very chemical way, proteins and peptides are crucial part of the coffee particularly for its flavor, aroma and tastes. The productions of number of by products like furans, pyridines, pyrazines, pyrroles and its derivatives in addition to Melanoidins are actually responsible for the color and flavor of the freshly brewed coffee. Further many of the biologic actions are also related to these component. Besides caffeine and Trigonelline the level of nitrogenous components is 10 – 16 % in the green variety. But definitely, coffee is certainly not protein enriched source of a diet. Surprisingly concerning the mineral level, it has high level of potassium (1 – 2 g / 100 g of green coffee). The other minerals are Na, Mg, Ca and S. The Mg content is higher in C. Arabica (~ 6 mg / 100g) whereas ~ 3 mg / 100 g in C. Robusta / C, Canephora.

Formation of bioactive amines, β-carbolines and amides – There are few minor products that could be counted as undesirable. The presence of biogenic amines is one of that item which is toxic by nature. In coffee, it is formed either by the action of microbial decarboxylases on amino acids. This unwanted fermentation happens due to inappropriate storage conditions or may occur during the roasting process which increases with time. The foremost ones are Putrescene, Spermidine and Spermine. In addition to those, several straight chains amines are also identified. Usually, they all have the unpleasant smell which stays hidden by the strong smell of caffeine and other ingredients in coffee.

Norharmane and Harmane are two heterocyclic alkaloids having structures like β – carbolines, with adjoining indole and pyridine ring. It is often noticed among the thermally processed foods. They are formed by the Pictet – Spenglar condensation reaction between indole-ethylamines (eg, Tryptophan) and carbonyls (eg, acetaldehyde or formaldehyde) followed by the oxidation and decarboxylation. The extent of productions depend on time and temperature of roasting event. They are identified in the roasted coffees (5 – 20 µg / 100 ml fresh brew). It is not a sure fact whether β – carbolines are beneficial or harmful for health. Studies have reported that β – carbolines isolated from the roasted coffees act as a reversible and competitive inhibitor of Monoamine oxidases (MAO -1 & MAO – 2), the enzymes intend to destroy all the neurotransmitter amines (eg, dopamine, serotonin, epinephrine, nor-epinephrine, melatonin etc). Inhibiting the enzymes enable to provide neural protection from Parkinson disorders, also controls anti-depression, anxiolytic actions, vaso-relaxation, blocking neuropathic pains, stimulating insulin secretion from the islets of Langerhans in pancreas, and anti HIV activity. As per its undesirable actions, β – carbolines might cause mutagenicity or genotoxicity. In addition, they induce addictive effect which is commonly noticed among the coffee drinkers.

Pictet – Spenglar reaction

The exact mechanism behind acrylamide formation in cooked or roasted foods never follow the similar path. So it still remain beyond our understanding. Its level in coffee depends on the roasting temperature. But it is higher in C. Robusta than C. Arabica. Interestingly, the level is high in light roast but it decreases with longer roasting. This event suggest that it is possibly formed during the early stage of Maillard reaction. Medium roasted coffee possesses ~ 1 µg / 100g whereas the dark roasted ones have ~ 0.5 µg / 100g. The generation of acrylamide is also being proposed due to the formation of sugar – asparagine adduct indicating a possible source from the initial stage of Maillard reaction. There is also an another probable route, which is by the decarboxylation of asparagine to 3 – amino-apropionamide that on further heating in absence of reducing sugar creates acrylamide.

Generation of Polycyclic aromatic hydrocarbons – These are formed during the roasting event particularly at high temperature around 220 – 260^oC. The level tends to increase with increment of temperature. The predominant components are Benzopyrene, Phenanthrene, Anthracene, Benzo-anthracene, Pyrene and Chrysene.

These are potentially carcinogenic compounds. Among them the highest carcinogenic effect is exerted by Benzo[α]pyrene. The presence of Chlorogenic acid in coffee is seen to inhibit the production during the roasting event. Their level is higher in dark roast (~ 2.5 ng / L) brew.

Benefits and risks of coffee: There are plenty of beneficial reasons for the drinking coffee which has been verified through scientific research and reported by the esteemed journals. In all respect, drinking of coffee in moderation, ~ 300 mg caffeine a day is safe enough for a normal adult without the healthy problem. But people with health issues should keep that level down. The major benefits of coffee are the following:

Benefits –

• About 2 cups of fresh brewed coffee can reduce exercise muscle pain ~ 48 %.
• Addition of fiber content to the diet; ~ 2 g of fiber / cup of coffee (recommended daily fiber intake ~ 30 g).
• Provides protection from the cirrhosis of liver but the effect is not due to caffeine.
• Lower the risk of type – 2 diabetes by ~ 10 %.
• The high level of caffeine in coffee protects against Alzheimer’s disease.
• Studies indicate that everyday coffee intake (~ 4 cups / day) considerably reduces depression level and lowers the risk of suicide.
• Drinking coffee lowers provides protection against Parkinson’s even when genetic factor come into play.
• About 4 cups / day could help protect against Multiple Sclerosis by preventing the possibility of neural inflammation.
• Epidemiological studies show that the habit of moderate coffee drinking lowers the risk of colorectal cancer by ~ 30 %.
• It is recently indicated that coffee might boost the women’s sex drive.
• Lowers the risk of liver cancer.
• Increased coffee consumption lowers the risk of gout in men.
• Coffee prevents retinal damage presumably due to chlorogenic acid.
• Drinking coffee without sugar and milk can lower the risk of dental cavities and other periodontal diseases.
• Studies indicate that coffee consumption can substantially reduce the risk of melanoma formation.
• Moderate consumption reduces the risk of heart attack.

Risks – Even having much beneficial role, coffee can impose few risks on health.

1. Drinking more than 6 cups / day causes addiction inducing anxiety and agitation.
2. Higher consumption causes restlessness, insomnia, increased heart palpitation and breathing rate.
3. People using coffee enemas creates huge side effects even death.
4. Caffeine enhances blood pressure within people suffering from hypertension.
5. Caffeine in coffee expedites the chances of osteoporosis within women since more calcium passes out of the body via urine.
6. Drinking excessive coffee might induce diarrhea and exacerbates the condition in the case of irritable bowel syndrome.

Paederia foetida / Stink vine / গ্যাঁদাল লতা

General features: It is a perennial climbing plant, native of India, Cambodia, Malaysia, Bangladesh, China and several other South East Asian nations. It can be found also in many of the Polynesian islands like Hawaii, Melanesia and Mascarenes. In English, it is commonly called Skunk vine or Stink vine for creating strong sulfurous odor if leaves or stems are crushed. The stem grows ~ 25 ft or more. Leaves opposite with petioles 2.5 in long. The leaf blades are oval to linear-laceolate ~ 4.5 in long and hairy, glaborous too often lobed at the base. The flowers are small grayish pink or lilac with petals of five which grow in clusters having the densely hairy corollas. The fruits are shiny brown ~ 2.5 in diameter. Flowers appear in October to January whereas the fruits grow during November to April. The plant is named Prasarini or Gandhali in Hindi and গ্যাঁদাল গাছ in Bengali. It belongs to the Rubiaceae family.  The fetid odor originates from the bruised leaves is due to the oozing of sulfurous compounds largely di-methyl sulfide, (CH₃)₂S. The leaves are generally used for variety of medicinal reasons as a folk medicine chiefly to control common intestinal problems like jaundice, diarrhea or dysentery. It is also counted to be an invigorator of male sexual health. Not much works are performed regarding its physiological or biological actions. It is realized that there are plenty of antioxidant and anti-inflammatory components existing within this herb. Experiments on animal indicate that it can enhance the production of semen as well as help secrete testerone displaying aphrodisiac or erectile effects. So far no toxic report is ever cited against this herb. The leaves are usually extracted for a number of medicinal uses. Besides to prevent intestinal ailments, the leaf extract is further used to control rheumatoid arthritis or in case of any problematic labors. As per extra interest, the herb offers youthful radiance to men possibly by virtue of its aphrodisiac action. Histological studies indicate that it promotes seminal vesicle and epididymal health and also increases the blood flow in testes. This actions improve penile erection index to a significant extent as compared to any other marketed drugs.

Significant bioactive components: Approximately, 77 components have been isolated from this herb. The total phenolic ingredients in the leaves are ~ 62.64 ± 1.32 mg /g of Ferulic acid equivalent whereas for stems the value is ~ 60.93 ± 3.40. The major bioactive chemicals are, Ursolic acid, sterols (Stigmasterol, Campesterol and Sitosterol), Hentriacontane, Hentriacontanol, Iridoid glycosides, Flavonoids, Ceryl alcohol, Methyl mercaptan, Palmitic acid, Paederine, paederone, Paederolone, and Paederenine. Although some of the components have been exactly identified but still many of them remain to be identified, like the flavonoids. The plant is enriched with phenolic ingredients but the exact nature is undetected. The reasonable explanation behind its anti-inflammatory action could be due to large flavonoid reserve. Followings are the major bioactive ingredients and their respective biological actions.

Ursolic acid, a pentacyclic tri-terpenoid has multiple beneficial action on health: 1) Inhibits cancer cell proliferation by inhibiting STAT3 activation pathway also induces apoptosis; 2) Decreases obesity; 3) Induces eryptosis; 4) Reduces muscle atrophy and stimulate its growth; 5) Helps improve cognitive function; 6) Helps regeneration of liver cells; 7) Enhances β – cell function for diabetic patients.

Stigmasterol is a precursor of Progesterone which is a valuable hormone playing many important physiological role related to Estrogen effects. It is also used during biosynthesis of Androgen, Corticoids and Vitamin D₃. It helps preventing prostate, breast, ovarian and colon cancers. Like other phytosterols it inhibits cholesterol absorption and reduces the serum cholesterol level. It also has strong anti-oxidant, hypoglycemic and thyroid inhibiting role.

Campesterol has potent anti-inflammatory effect and works particularly well for osteoarthritis patients. It also has the lowering effect on cholesterol and LDL level in serum. It is a precursor of anabolic steroid Boldenone.

β – Sitosterol it is very effective in reducing Benign Prostate Hyperplasia and also able to reduce cholesterol and LDL level in serum.

 

Hentriacontane [(CH₃) – (CH₂)₂₉ – (CH₃)], alkane hydrocarbon which can be found in some other plants including bees wax. It has strong non-proliferating role on gastric cancer.

Iridoid glycosides – Aucubin is one of them cited as an example found in many plants of Rubiaceae family.

 

Iridoid glycosides are actually the secondary metabolites in many plants especially belonging to the Apocynaceae, Lamiaceae, Rubiaceae families. The iridoids exhibit wide range of medicinal effects like cardiovascular, anti-inflammatory, hepatoprotection, hypoglycemic, antimutagenic, antispasmodic, anti-tumor, antiviral, immunomodulatory and laxative. Iridoids are monoterpenes synthesized within those plants acting as a defensive agent against pests and diseases. It is seen to act preventing the progression of Alzheimer’s disorders. The mechanism of their actions are noticed to be through the blocking of various pro-inflammatory cytokines.

The exact role of Methyl mercaptan and Ceryl alcohol are not yet identified. It is possible that CH₃SH or its oxidation product (CH₃)₂S could act as intermediate for further chemical reactions due to its nucleophile nature. It can act as a powerful anti-oxidant.

Pederin / Paederine – or any of its analogs could be identified in some cases of beetles’ larva. A majority of them have almost the similar structure and are identified in this herb. The compound has potent anticancer effect. The compound Pederin is tried as anticancer drug. It blocks mitosis even at extreme low doses (1 ng / ml) by inhibiting DNA without preventing the RNA synthesis. It is used for the treatment of several cancers or solid tumors.

Pharmacological actions: A great many number of pharmacological experiments are conducted assuring the beneficial role of this herb. Several of them are cited below.

Antidiarrheal effect – Experiments on animal legitimizes the fact that ethanolic extract of Paederia foetida can efficiently prevent diarrhea when used doses of 100 – 500 mg / Kg. Further experiments also revealed that this anti-diarrheal action occurs due to the inhibition of intestinal motility.

Aphrodisiac effect – Experiments using sexually mature male rats have confirmed significant level of increase in mounting frequency with simultaneous decrease of mounting latency, paired with tremendous enhancement of intromission frequency and decrease of intromission latency. These effects are dose-dependent and the peak value is achieved after 28 days of using 200 mg / Kg of ethanolic extract. It is very comparable to the active control of 0.5 mg / Kg of testerone injections biweekly. The effect could be due to the rise of testerone.

Effect on testerone level – The increase of serum testerone level is noticed when applied to the normal healthy rats (100 – 200 mg /Kg) for 28 days. The level rises to 4.0 – 5.0 ng / ml compared to the control which is 1.8 – 2.0 ng / ml. The rise can only be visualized after at least 15 days among the groups getting the highest doses.

Effect on testes, Penis and Prostate – The administration of ethanolic extract (50 – 200 mg / Kg) for 28 days increases the weight of testes (~ 6.0 %), epididymis (~ 10 %) and seminal vesicles (~ 8.0 %). The histological examination indicates a potent vasodilatory effect along with increased spermatid levels within testes with simultaneous enlargement of Sertoli cells. Similar studies also indicate an increase of penile erection index (~ 200 %) after 15 days of administration whereas after 28 days the increment is ~ 300 %. Both outperform the testerone control (0.5 mg / Kg) biweekly. No significant enhancement regarding the sizes of prostate have been reported.

Anti-oxidant effect – The fresh leaf extract shows potent antioxidative effect during in vitro assays which is much greater than quercitin but less than Vitamin E. In course of free radical scavenging test it also stays higher than quercitin but slightly lesser than Vitamin C.

Anti-inflammatory effect – The herb has strong anti-inflammatory effect which is proven by granuloma formation test in the test mice. It shows higher potency than the phenyl butazone.

Miscellaneous effects – The following effects are conducted in human subjects.

1. Thrombolytic action is significant although somewhat less than the Streptokinase.
2. Cytotoxic action is also very noteworthy but much less than the vincristine.
3. The dose dependent decrease of blood glucose level have been observed which is almost comparable to Metformin.

Bitter Melon / Momordica Charantia / करेली / উচ্ছে

General features: The plant is a tropical / subtropical vine of versatile nature which often bears diverse shapes and sizes of fruits. The scientific / botanical name is Momordica Charantia which is commonly known in the English as bitter melon / bitter gourd / bitter squash which is actually a vegetable. Besides fruits, young leaves of the plant are also effective offering multiple medicinal values, particularly in the field of diabetes. The plant draws huge attention owing to the rising problem of diabetes throughout the recent world. A great number of phytochemicals have been isolated from this plant and fruit that display versatile medicinal role curing or preventing number of diseases and disorders. The fruits are commonly used as a diet rather than the leaves. In Hindi it is called Kareli whereas in Bengali, it is termed as Uchche (উচ্ছে). The plant belongs to the Cucurbitaceae family that grows mainly in the South East Asia, Caribbean and Africa. Despite its extreme to moderate bitterness, all varieties are popular in India and other nations. Type -1 and – 3 are highly bitter in taste but type-2 is somewhat less compared to the others which is commonly called Chinese bitter melon. Type -1 and – 3 have crinkled surface but type -2 is relatively smooth on that regard. On the other hand, type – 3 is much smaller in size but extremely bitter in taste. Even having the strong bitterness, all of them are considered as precious vegetable in India. They are often included in the daily diet in many regions of India because of the immense benefits on health. The fresh leaves are also frequently introduced to the cooking along with other spicy vegetables. The use and cultivation of bitter melon are thought to be originated in India around 14th century and afterward transferred to China and other South East Asian nations. In recent days, it is extensively used in many South East Asian cuisines. The vine grows ~ 16 – 20 ft in long bearing simple alternate leaves ~2 – 5 in length with 3 or 7 separated lobes. The plant is bisexual by nature and grows both male and female flowers at a time that bloom between June and July whereas fruits appear around the time of fall. The fruit has warty exterior irrespective of the shapes having hollow cross-section. It is used as vegetable while being green. The thick skin is mostly used for the edible needs which is intensely bitter in taste. If fully ripe, the fruit turns orange whereas the inside becomes bright red in color and bitterness disappears. At this point, it spurts exposing the matured seeds and red pulp.

Use as folk medicine:  The medicinal use of bitter melon is known since Ayurvedic era. In South East Asian, Caribbean and African nations the use of fruits and plants as herbal / folk medicine has been widely known particularly in the case of stomachic, diabetes, laxative, emetic, anthelmintic, ulcer, gout, rheumatism, skin diseases, cough and common respiratory problems. It is further claimed to have a preventive role in cancers, HIV, AIDS and few other fatal infections. The role of bitter melon and its leaves and plants on diabetes is almost legendary. Despite its various beneficial actions particularly on diabetes and also the protective role toward many ailments, a section of people in India are not so fond of this vegetable owing to its bitterness, a very common trend especially among the children. According to the animal studies, daily consumption of fresh green fruits or its extract produce potent hypoglycemic effect by lowering the circulating glucose level. Studies conducted on human in England and other parts of the world confirmed significant (~ 50 %) lowering of either the fasting glucose level or A1C in plasma for both type -2 and type -1 diabetic patients if consumed for approximately seven weeks period. The fall in glucose level is noticed for both post prandial (~ 25 %) as well as in the fasting conditions. Interestingly, the seed extract is seen more effective to lower the post prandial level almost ~ 48 %. From the very earlier period and also as per concerning the folk belief, bitter melon is always considered as an effective agent against diabetes, for both insulin and non-insulin dependent cases. Researchers show that the extract stimulate insulin secretion by activating insulin producing pancreatic β – cells additionally it also causes the excretion and absorption of bile. It has been further claimed that it helps digestion of carbohydrate and simultaneously lowers the level of blood glucose. Besides the fresh green fruits, young leaves are also potent in that act. Recently, a number of phyto-compounds have been isolated and characterized from the extracts of bitter melon and its young leaves that definitely show prominent antidiabetic effects. Additionally, the seed extract from ripen fruits has shown preventive actions against cancer cell proliferation in vitro. Besides its wide use among the Indian and Chinese population, it is also used in many South American nations. In Amazonian area, leaf tea prepared by drying fresh green leaves are used for diabetes, intestinal discomfort and promoting regular menstruation. It is also used against viral fever, wounds, infections, worms and parasite infestations within intestine. Traditionally, its use is noticed among the indigenous population of Amazonian area. The plants, fruits, leaves and roots are conventionally consumed according to the Brazilian herbal medicine against rheumatism, wounds, malaria, inflammation, diabetes, menstrual problems, vaginal discharge, colic, fevers and intestinal worms. The extract acts as abortifacient as well as an aphrodisiac. It can also act as a remedy toward the skin problems, vaginitis, hemorrhoids, scabies eczema, and leprosy and itch rashes. In Mexico and Peru, the plant itself is used against treating diabetes, measles, malaria, worms and inflammation. In Nicaragua and other Latino countries, the leaf is used against stomach pain, diabetes, fevers, colds, malaria, headaches, menstrual disorders, hypertension, pain, infections and also as an aid during childbirth.

Culinary use: Throughout the Asian nations the culinary use of bitter melon is highly common. In most parts of India like in West Bengal, it is used in the curry along with other vegetables. Occasionally, its fresh green leaves are also admitted in the cooking.  In North Indian cuisines, it is often served as stir fried vegetable and cold yogurt for dip to remove away some of the bitterness. It is also served as deep fried stuffed vegetable filled with hot spices. In many Southern Indian cuisines, bitter melon is used for making soups which is considered to be healthy. In some parts of India, the vegetable is pickled and roasted after sprinkling with salts and oils before eating. In Srilanka it is fried, cooked and served with coconut and rice. It is popular even in Chinese cooking which values for its bitter taste and flavor therefore often served as stir fried vegetable and shredded pork. It is also used in place of hops during making the bear in China. In Pakistan and many West Indian states, it is cooked with onions, garlic and hot spices to be served with rice.

Phyto-components in bitter melon / Momordica Charantia – Table -1

Compounds	Nature of compounds	Plant part
Amino acids	Amino acids	Fruits & Seeds
Arachidic acid	Lipid	Entire plant
Ascorbic acid	Organic acid / Vit. C	Fruits & Leaves
Ascorbigen	Alkaloid	Fruit
β-amyrin	Triterpene	Seed
Peptide inhibitors	Peptide	Seed
GABA	Amino acid	Fruits & Seeds
Calciolarioside E	Phenyl propenoid	Leaves and plants
Capric acid	Lipid / fatty acid	Seed oil
β-carotene and its derivatives	Carotenoid	Pericarp
Charantin	Steroid	Fruit, Seed
Charine	Alkaloid	Unripe fruit
Cholesterol	Lipid	Fruit
Various plant steroids	Steroids	Fruit, Seed, Pericarp
Various triterpene & its derivatives	Triterpene	Fruit, Leaves, seeds.
p-cymene	Monoterpene	Seed
Pentacyclic triterpenes	Terpenes	Fruits, seeds & leaves.
Minerals	Inorganic	Fruits & Leaves

Important Phyto-constituents – Table – 2

Source	Phytochemicals
Plant body	Momorcharins, Momordenol, Momordicilin, Momordicins, Momordin, Momordolol, Charantin, Charine, Cryptoxanthin, Cucurbitins, Cucurbitacins, Cucurbitanes, Cycloartenols, Diosgenin, Elaeostearic acid, Erythrodiol, Galactouronic acids, Gentisic acid, Goyaglycosides, Goyasaponins, Multiflorenol.
Plant body	Glycosides, Saponins, Alkaloids, Oils, Peptides, Terpenes and sterols.
Fruit	Momordicine, Charantin, Polypeptide – p – insulin, Ascorbigen. Amino acids, GABA and Fatty acids (Lauric, Myristic, Palmitic, Stearic, Linoleic & Linolenic).
Seeds	Amino acids & Urease.

 Phytochemistry: The bitter melon / Momordica Charantia synthesizes large number of phyto-chemicals belonging to the family of glycosides, saponins, alkaloids, terpenes, steroids as well as proteins. The fruit is also a good reservoir of vitamin C (~ 40 mg / 100 g), vitamin A (~ 1500 µg / 100 g), iron (~ 0.5mg / 100g) and phosphorous (~ 320 mg / 100). The major biologically active compounds isolated either from fruits or leaves are Momorcharins, Momordenol, Momordicilin, Momordicins, Momordicinin, Momordin, Momordolol, Charantin, Charine, Cryptoxanthin, Cucurbitins, Cucurbitacins, Cucurbitanes, Cycloartenols, Diosgenin, Elaeostearic acid, Erythrodiol, Galacturonic acids, Gentisic acid, Goyaglycosides, Goyasaponins and Multiflorenol. The hypoglycemic effect is caused due to the mixed effect of Charantins, insulin like peptides and alkaloids. Studies also identified two types of components in the fruit extract, one is fast acting whereas the other(s) exert longer lasting hypoglycemic or anti-hyperglycemic effect. Additionally, a polypeptide titled, p-insulin isolated from the fruit extract has shown strong hypoglycemic effect in human and animal when injected subcutaneously. It is very amazing that the plant is a huge reservoir of triterpene and among them a large section is pentacyclic by nature. The scientific surprise which appears at the beginning of last century is the isolation of insulin like polypeptide from bitter melon fruits and leaves despite the existence of number of bioactive terpenes that can also efficiently lower the blood glucose level. Besides remarkable anti-diabetic role the plant, fruits and leaves offer diverse biologic effects, beneficial for maintaining good health.

Charine shows chemo-preventive actions. Cucurbitin, this carboxy pyrrolidone compound can efficiently kill parasitic flat worms. Cucurbitacin is not only anti-inflammatory but it also has potential preventive actions on several cancers, diabetes and cardiovascular diseases. Ascorbigen is an inducer of detoxifying enzymes for destroying xenobiotics. TCD, a triterpene is highly effective against bone marrow and breast cancer cells (MCF-7, mDA-MP-231). Calciolarioside produces protective effects against any cytotoxicity by enhancing Bcl-2 expression. It also increases expression of antioxidant molecule helping decrease the level of ROS generation.

Pharmacological effects: The use of Momordica Charantia / bitter melon particularly in India is noticeably very common. It exists almost six out of ten household diets in dinner. The age old practice of using fruits, leaves or stems is continuing unabated as an important vegetable to be consumed, for its widely known beneficial effects on health. A vast number of researches are in progress evaluating the medicinal nature and future prospects of each of the phyto-components.

Anti-diabetic effect – In recent days due to the prevalence of high incidences of diabetes, attention toward bitter melon turns deeper although the plant qualifies to offer a lot more than that. For a long time its role against diabetes is almost mythical. The hypoglycemic compounds identified in the fruit are steroidal saponins (Charantin), insulin like peptides (Polypeptide – p) and alkaloids. Both individually and jointly exert hypoglycemic action. It is the concerted action makes the fruit more effective in lowering the blood glucose level. The in vivo studies regarding hypoglycemic role of bitter melon has been extensively conducted by a large group of Scientists in Japan. They have isolated more than eleven triterpenoids which show efficient hypoglycemic actions in human. Some of the components offer extreme bitter tastes like Momordicine and its analogs and Momordicosides K and L. Seemingly, the extent of taste varies according to the glucoside linkage position.  Momordicosides have several analogs but all are not bitter in taste.

Charantin – It is a triterpenoid glycoside from bitter melon that displays potent anti-diabetic effect. Studies showed that it is far more effective than the oral hypoglycemic compound Tolbutamide (Sulfonyl urea derivative works by stimulating insulin from the pancreatic β-cells). The experiments suggest that it offers protective action on insulin producing β – cells, declines non-fasting blood glucose, glucose tolerance, and insulin resistance, and promotes insulin sensitivity by helping the expression of GLUT4 in skeletal muscles. The overall hypoglycemic effect indicates its effectivity toward type – 2 is more rather than the type – 1 diabetes or against the dysfunction of β – cells.

Insulin like polypeptide – p – It is a plant based peptide found in the bitter melon that enables to induce hypoglycemic effect like the normal Insulin, if injected subcutaneously. It has been recently cloned showing 498 bps gene coding for the bitter melon. Experimentally, the oral use of the recombinant protein induces hypoglycemic effect in Streptozotocin induced diabetic rats indicating its usability to treat also the type-1 diabetes. It is very effective toward the human.

Vicine – The compound is an alkaloid which is active against hyperglycemia intending to regulate the rise of blood glucose. But as per its adversarial effect, the pure compound is seen frequently to induce hemolytic anemia especially to those having hereditary lack of Glucose – 6 – phosphate dehydrogenase. Although there is no such report available even after age old use of the fruit producing any such problem but precautions should be taken especially if any one possesses that genetic deficiency.

 

The extensive studies regarding the effect of bitter melon extract on regulating diabetes reveals the following major facts concerning the pharmacological role behind its hypoglycemic action:

• Stimulation of peripheral and skeletal muscle glucose utilization.
• Inhibition of intestinal glucose uptake.
• Inhibition of adipocyte differentiation.
• Suppression of key gluconeogenic enzymes.
• Stimulation of key enzymes of HMP pathway.
• Preservation of pancreatic β – cells and its integrity.

Studies further reveal that the extract of bitter melon stimulates insulin secretion when orally fed to the STZ induced diabetic rats. The suppression of MAPK including SAPK / JNK, p38, p44 / 42 including NF – κβ and several others are identified to be the leading cause behind those actions. The extract is seen also effective in preventing the neuronal injury among the diabetic patients.

 

Anticancer effect – Studies using the extract or purified analogs show strong anti-cancer actions when applied to various carcinomas like lymphoid leukemia, choriocarcinoma, melanoma, breast cancers, skin tumor, prostatic cancers, squamous carcinoma of tongue and larynx, and human bladder carcinoma and Hodgkin’s disease. Detail works indicate that in most cases inhibition of cell cycle at G2 or M phase is involved. In some occasions, inhibition of guanylate cyclase, activation of NK cells and induction of apoptosis are also observed to control the cancer cell proliferation.

Antiulcer action – The extract shows potent anti-ulcer actions both in vivo and in vitro. The compound Momordin Ic (10 mg / kg) inhibits ethanol induced gastric mucosal lesions. It is further interesting to observe that fruit extract has strong anti H. pylori effect. It adds great benefits regarding the prevention and control of all types of stomach ulcers.

Hypotensive and anti-prothrombin action – The extract shows mild hypotensive action which is possibly caused by Momordin. It also prevents prothrombin activation significantly due to its inhibiting action of factor X by factor VIIa. In that way, it has preventive role on blood clotting action.

Anti-psoriasis effect – The extract inhibits the enzyme action of Guanylate cyclase which is seemingly the leading cause behind preventing role on psoriasis.

Miscellaneous effects:

Anthelmintic, Anti-malarial, Immunomodulatory, Hypo-cholesteromic, Antioxidant, Analgesic and Anti-inflammatory.

Toxicity: No significant toxic effect is ever reported regarding liver or kidney. The observed adverse effects are related to hypoglycemic convulsions among the children and abortifacient actions on pregnant women.

 

Spinach / Spinacia Oleracea L / পালং শাক্

General features: The botanical name is Spinacia Oleracea L which is commonly known as Spinach in the English world and পালং শাক in Bengali. The plant belongs to Chenopodiaceous / Amaranthaceae family. It is a small flowering plant, which by nature is fully edible therefore being consumed over a long period of history. Either being whole plant or the fresh leaves are often included in diet as cooked or uncooked vegetable, like the use of baby spinach in salad. Spinach stands as number three rank in the list of World Health Foods having high nutritional value. The origin of spinach is guessed to be in the Central and Western Asian temperate zones, from which it is spread over the entire globe for its popularity owing to enormous nutritional and health benefits. Although considered to be annual but the plant often grows biennially at many regions particularly in the South East Asian nations like, India, Malay, Indonesia, Thailand, China and Vietnam. The plant grows ~ 1 – 1.5 ft tall. The leaves vary in sizes ~ 2 – 12 in long and 1- 6 in width depending on the nature of species. As per its shape, they are alternate and ovate or slightly triangular form. The flowers are yellowish green, ~ 0.2 – 0.3 inch diameter. The fruits (diameter ~ 0.2 – 0.4 in) are lumpy and clustered having numerous seeds inside. The English word “Spinach” is thought to be evolved from the French, Espinache or Epinard, which also might originate from the Latin or Catalan word, Espinac. Currently, few varieties of spinachs are grown for the vegetable needs. Savoy is one of them, which does not possess the smooth leaves but it is resistant to bolting. Another variety is Merlo Nero which is somewhat mild by the taste and being slightly smaller in size. The other old and larger type has smooth and broad leaves that is mostly processed for canning or frozen to store longer for the future use. The type, Virofly grows larger in size and shows high in production. It is majorly cultivated in India and other South East nations. Occasionally, it displays purple touch in their leaves. The very recent type is semi Savoy which is a hybrid by nature having less crinkled leaves. The world production of Spinach is ~ 24 million tonnes / yr, according to the statistics of 2014.  Among the countries, China alone grows the highest, ~ 91 % (~ 22 million tonnes / yr) whereas other nations including the US, each one of them individually grows less than ~ 1 % or ~ 0.5 million tonnes / yr. According to the recent food survey report around the globe, spinach is often identified being heavily contaminated with numerous pesticides which is really a worrisome factor, so definitely it needs to be thoroughly washed before any way of its consumption. The report further indicates that spinach from various sources are often seen to be contaminated with high level of Cd. In this situation soil should be tested before its plantation. The fresh greens lose major nutritional benefits within few days after taken out of the field. The use of refrigeration delays the process for only about a week or so. The major loss is noticed in the case of folate and carotenoid content. The snap freeze or deep freeze from freshly collected plants can preserve the nutritional contents for almost eight months. In many occasions, the fresh ones are packaged under nitrogen gas to enhance the shelve life. As per frequent practice, spinachs are routinely irradiated before packaging for the sake of sanitization. It raises doubt to many as a suspicion for losing any nutritional benefits but in practice no such loss has been detected when 4.0 K Gy level of radiation (1.0 Joule / Kg of the matter) is applied which is, approved by the FDA in US. The level of Vitamin C, E, K and B₉ and carotenoids especially the Neoxanthin remain unchanged even the radiation level is further enhanced.

History of spinach use: This leafy vegetable is believed to be a native of Persia. Its exact time of arrival in India and other South East Asian nations remains unknown. But as a logical speculation, spinach is thought to be appeared in the Indian subcontinent through the invasion by Persians around eighth century AD. Later, it crossed to the China via Nepal. It was around the same time, spinach was introduced in Italy (Sicily) also by the Persians. The written evidence of spinach use and its benefits was first identified in the tenth century medical works by al-Razi and also in the agricultural treatises by ibn-Wahshiyah and Qustus al-Rumi. In later future, around twelve century AD it was launched in Spain also by the Persians. There it was once regarded as being the chief of all leafy greens. In the eleventh century, spinach was mentioned in a special agricultural treatise by ibn-Hajjaj. From thirteenth to sixteenth century, spinach appeared almost everywhere in the Europe. Its use was mentioned in many English cook books and considered to be a favorite vegetable of famous Catherine de Medici, Florence born queen of France and also the wife of King Henry II. It was her breakfast dish on bed, earned the name Florentine, following her native place. Due to high iron content, during WWI, spinach was frequently offered to the wounded hemorrhaging soldiers.

General nutritional fact: The plant is considered as a vegetable and also regarded to be the healthiest food known so far. It is densely populated with innumerable nutrients while offering less calories. It synthesizes numerous antioxidants, mostly flavonoids along with multitudes of other nutrients. It delays aging and also age related macular degeneration while also providing protection to CNS by preventing any inflammatory actions and also boosting the immune system. Additionally, its high carotenoid content adds further protections against the diseases like cancers, cardio vascular problems, diabetes, neurodegenerative illnesses, obesity and many others. The major carotenoids identified in spinachs are β – carotene, lutein and zeaxanthin.

Nutritional benefits and pharmacological concerns: Studies have already established the immense benefits of spinach for high level of phytonutrients, important vitamins and minerals which are water as well as fat soluble by nature. As per the rating of World Health Foods, spinach ranks as #1 for Mg and Fe, #2 for vitamin B2, B6, E and K, #3 for folate Ca, K and vitamin A, and #5 for the Mn. Additionally, the plant has large quantity of antioxidants and carotenoids. Recent works further indicate that spinach can retain most of its carotenoid content intact during sautéing except a minor amount is lost while frying and boiling. Interestingly, study shows that insignificant amount of vitamin C within spinach undergoes any damages even after boiling for five minutes in water whereas the use of microwave causes more loss to the vegetable. About 10 – 20 % folate contents are seen being lost during traditional cooking. Several studies also focus on the presence of nitrate (- NO₃) which is identified to be in the range of ~1.0 mg / 227 g, not as an additive or outside contaminant. Surprisingly, instead of imposing any adverse role, this level of – NO₃ provides positive effects. Its conversion to – NO₂ by bacteria and finally to NO offers a protective role on intestinal lining. Spinach is also an enriched source of chlorophyll (25 mg / 227 g). The chlorophyll containing chloroplast and its associated thylakoid membrane offers potential health benefits. Studies show that thylakoid enriched extract of spinach can delay the stomach emptying, decrease hunger inducing hormone Ghrelin but enhance the satiety related hormone, Glucagon like peptide – 1 (GLP – 1). Possibly, in that way spinach enables to prevent obesity. In recent days, peptide mimetics (Albiglutide, Exanatide, Dulaglutide or Liraglutide) acting as agonist of GLP-1 are routinely used as medicine to control the Type – 2 diabetes. It is speculated that consumption of thylakoid membrane influences the satiety signal inside hypothalamus due to increased level of pancreatic enzymes along with CCK, leptin and ghrelin which eventually lowers the absorption of carbohydrate and fat. Spinach also synthesizes large quantity of Oxalate (-OOC – COO-^-2) which raises a strong suspicion for its efficiency to deplete the dietary as well as circulating Ca⁺². So individuals who are predisposed for gout disorders and babies smaller than four months should stay away for its consumption.

Major Phytochemicals: Among the phytochemicals, major ingredients are flavonoids and carotenoids along with substantial levels of mineral and vitamins. The common flavonoids identified in spinachs are quercitin, kaempferol, myricetin, apigenin, luteolin and Patuletin.

 

In addition to those, there exists few methoxy derivatives of flavonoids, which also often show the glycoside linkages. The CH₃O- derivatives are Patuletin, spinacetin and jaceidin. The flavonoids are powerful antioxidants which provide physiological protection for fighting against any free radical damages by way of quenching.

Among carotenoids the notable ones are β – carotene, lutein and zeaxanthin which are presumably the precursor of Vitamin – A.

The carotenoids are synthesized at high level in spinachs to modulate absorbed light energy for dealing the triplet / excited state of chlorophyll, which is often over produced in the process of photosynthesis.

Mineral content / 30 g of fresh spinach

Minerals	Amount
Calcium	30 mg
Iron	1.0 mg
Magnesium	24 mg
Phosphorous	15 mg
Potassium	170 mg
Sodium	24 mg
Zinc	0.2 mg
Copper	0.0 mg
Manganese	0.3 mg
Selenium	0.3 µg

Vitamin content / 30 g spinach

Vitamins	Quantity
Vit. A	2813 IU
Vit. C	8.5 mg
Vit. E	0.6 mg
Vit. K	150 µg
Riboflavin	0.1 mg

Fats and fatty acid content / 30 g

Fats and fatty acids	Quantity
Saturated	0.0 mg
Ω – 3 fatty acid	45 mg
Ω – 6 fatty acid	8.0 mg

Physiological and pharmacological actions: A number of surveys affirm the diverse beneficial actions of spinach which is attributed from the antioxidant role. The routine use of spinach in diet increases the plasma level of lutein, β – carotene and retinol but interestingly, the anti-oxidant action is not enhanced to the projected extent. Epidemiological studies have shown its non-proliferative effect on various cancers. The extract prevents multiplicity of papillomas in the mouse model. As a further measure, same extract inhibits the proliferation of human prostate and gastric cancer cells. Interestingly, the glycolipid fraction of spinach is seen to inhibit angiogenesis of several human cancer cells implanted in the mouse. Clinical experiments also indicate that consuming powdered spinach for about two weeks curbs the DNA strand break. It is perhaps an indication behind its cancer prevention role by diminishing oxidative damages.

Regarding the cardiovascular problems, diet enriched with folate enhances its level in circulation which in effect lowers the extent of homocysteine which is an indication of reduced cardiovascular risk pointed out by widely famed Framingham study. Since spinach is enriched with folate so logically it imposes beneficial effect on cardio vascular problems. Animal experiments further demonstrate that spinach is able to prevent cognitive dysfunction and also age related motor or cognitive deficits within CNS. Similar experiments also indicate that feeding spinach in daily diet can delay the Alzheimer’s disorder. Its potent anti-inflammatory action is considered to be responsible for this beneficial role. It is established that xanthophylls improve the night vision in addition to adaptation in dusk. Spinach has high level of xanthines like zeaxanthin, lutein or β – carotene. Usually, lutein and zeaxanthin accumulate within the macula which in turn prevents the tissue damage by UV or blue rays. The compounds also prevents age related macular degeneration and cataract formation. The inhibition of lipid peroxidation and subsequent free radical scavenging is thought to be a possible mechanism behind this act. In overall perspectives, the antioxidants like flavonoids, carotenoids and others are known to help maintain the integrity of immune system by scavenging the reactive oxygen species and free radicals. Considering its further use, spinach is recently in use as a vehicle for raising vaccines against Anthrax, HIV and several others.

 

Moringa Oleifera / সজনে গাছ

General Features: The plant Moringa Oleifera is a species belonging to Moringaceae family of Moringa genus. The name Moringa originates from the word ‘Murungai’, a Tamil word for drumstick. In English, it is often called ‘Drumstick’ tree due its long and slim seed-pods. In Bengali, it is labelled as ‘Sajne / সজনে’ tree. In African Nile valley, it is called ‘Shagara Rauwaq’ meaning, a tree destined to purify. It is highly acclaimed in the Pakistan naming ‘Sohanjna”. The tree has been mentioned even in the “Shushruta Sanhita” the ancient Indian Materia Medica, as “Shigon” notifying its use and cultivation, dating back to the early days of India before the first century AD. In some parts of India, oils are also extracted from the dried seeds for numerous uses. The tree grows in tropical and subtropical region of India and many Southeast Asian nations, mostly cultivated for the sake of herbal medicine, water purification, preparing hand washing detergents and various cosmetic uses. It is a draught resistant tree that grows mainly in the wild. Only in recent days, it is orderly cultivated for use as vegetable that includes leaves, flowers and drumsticks. Besides the South East Asian nations, it also grows in many regions of tropical Africa. It is a deciduous tree reaching ~ 40 ft height above the ground spreading trunks of ~ 1- 2 ft diameter. The bark is whitish grey in color surrounded by the thick cork. The young shoots have purplish to greenish white hairy bark. The fragile branches have tri-pinnate leaves showing feathery foliage. The flowers are fragrant and bi-sexual having yellowish petals. They are ~ ½ in long and ¾ in wide growing in clusters. Flowering starts after six months of planting. In semi cool regions of Northern India near the Himalayan range, flowering occurs once in a year but under constant tropical conditions that takes place 2 – 3 times in a year or else the entire year around. The fruits are seed-pods often described as ‘drumsticks’ which are 1 – 1.5 ft long and ~ 0.25 in diameter. The tree grows in tropical or subtropical regions in slightly acidic to neutral sandy well-drained soil with pH 6.5 – 7.0 under sunny, hot and bright climate. It does not tolerate the cold or freezing temperature at all. India is the largest producer having ~ 1.5 million tonnes of Moringa seed pods / drumsticks per year. In India, it grows largely in the West Bengal, Orissa, Andhra Pradesh, Tamilnadu, Karnataka and few of the North East regions. Currently its cultivation is started also in Hawaii. Usually, seed-pods / drumsticks, leaves, flowers and occasionally the young roots are consumed in the daily diet. The oil extracted from the matured and dried seeds also finds uses as food supplement or for the preparation of cosmetics to maintain natural gloss of hair or preserving the better texture of skin.

Uses and nutritional factors: According to the UN’s world nutritional program, Moringa tree is considered as tropical crops in several African and Asian nations. It is considered to be the most underutilized crops, even though scientifically it is accounted to be an effective source of nutrients for all the ages. During crisis management, the health workers in Haiti and Senegal frequently treat malnutrition among children, pregnant and nursing mothers using powdered leaves which is a significant source of vitamins, minerals and proteins. It is reported that ~ 8 gm of powder is appropriate for the children belonging to 1- 3 years of ages providing, protein ~15 %, required Ca ~ 40 % required Fe ~ 23 % and required vitamin A ~ 100 % per day. About 100 gm of leaves provide a woman ~ 1/3 of her daily need of Ca and good quantities of Fe, Cu, S, vitamins and proteins. In a way, using the leaves of Moringa Oleifera as a vegetable in daily diet would enable to help solve the malnutrition crisis of many developing nations. Besides leaves, other parts of the plant, like immature / green seed-pods termed ‘drumsticks’, flowers, mature seeds and extracted oil can be utilized for dietary purposes. Among those items, leaves carry the most nutrition. It is a significant source of Vitamin B, Vitamin C, Vitamin A, Vitamin K, and β – Carotene, proteins and several important minerals including Mn. It also provides adequate quantities of flavonoids, poly-phenols as a viable source of antioxidant. In some Asian countries like Philippines, it is named as ‘Mother’s best friend’ for enabling to increase the quantity of breast milk during nursing and also helping prevent anemia. The green leaves can be cooked like a vegetable resembling to Spinach. The ‘drumsticks’ or immature seed-pods are highly appreciated in soups / curry which are noticed in many South East Asian cuisines. It offers good amount of Vitamin C, K, Mg, Mn and dietary fibers. The roots from small plants are also occasionally consumed as a condiment for its sharp flavor due to high level of polyphenols.  In some regions, seeds after removing from the matured pods are roasted and eaten like peas. It has high level of vitamin C, B and dietary minerals. The crushed matured seeds provide ~ 40 % of edible oil which is clear, odorless and interestingly, resistant to the rancidity.

Commercial use of waste water purifications: The seed cake created after the oil extraction is commercially used in recent days to clean water for the drinking needs. It is also applied for the sewage and industrial waste water treatments. The mature seed-pods contain dimeric cationic proteins (M_w ~ 6.5 KDa / subunit, pI > 9.8) that help enhance the coagulation and flocculation process with superb efficiency removing majority of suspended undesired components / pollutants from the uncleaned water. The efficiency is higher than Alum. Over and above, the proteins display potent antimicrobial effect by fusing and disrupting the bacterial surface membrane imposing lysis and death. They are non-toxic thus exerts no adverse effects on the health. Interestingly, they can tolerate very high temperature ~ 95⁰C even when heated for > 5hrs. The amino sequences of cationic polypeptides,

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[Red – cationic amino acid, Arginine, Glutamine and Asparagine; Green – acidic amino acid, Aspartic acid, blue – partially cationic amino acid, Histidine].

Further, the seed suspension can remove Cd⁺² from the aqueous environment thereby helping purify drinking water freeing from Cd contamination. The suspension has organic acids that have the ability to bind the metal ion.

Medicinal effects: Almost every part of the tree is valuable, roots, leaves, fruits (Pods / ‘Drumsticks’), bark, flowers, seeds, gum and seeds. Seeds are often used for making oil to prevent or cure numerous ailments like indigenous / folk medicine in certain regions of South East Asia to treat cardiovascular, inflammatory, infectious, gastro-intestinal, hematological and hepato-renal diseases and disorders. Additionally, its versatile utility as a good and cheap vegetable source of protein, nutraceutical and waste water management makes it to be a unique plant known so far. Below is the table of various medicinal uses of different parts of Moringa Oleifera tree.

Parts of the plant	Medicinal uses
Leaves	Laxative, Application of poultice to sores, Rubbing on the temple during headache, Used for hemorrhoids, fevers, sore throat, bronchitis, eye & ear problems, infections, Scurvy, Anti-diabetic, helps lowering the swelling of glands.
Flower	Acts as aphrodisiac, Stimulant, Abortifacient, Cholagogue, Curing muscle disorder, Anti-inflammatory, Anti-tumor, preventing enlargement of spleen, Lowering serum Cholesterol, Lipids, Triglyceride, VLDL, LDL, Cholesterol to lipid ratio, enhancing the excretion of fecal cholesterol.
Root	Antilithic, Rubefacient, Vesicant, Carminative, Anti-fertility, Anti-inflammatory, Stimulant, Cardiac-circulatory tonic, Laxative, Abortifacient, Anti-rheumatic, Lower articular pains, Lower pain in the kidney.
Seeds	Seed extract lowers lipid peroxides in liver, Anti-hypertensive effects.
Gum	Used for dental caries, Rubefacient, Acting against headache, Fever, Intestinal complaints, Dysentery, Asthma, Treatment for Syphilis and rheumatism.
Stem bark	Rubefacient, Vesicant, Cure for eye diseases, Helps during delirium, Prevents enlargement of spleen, prevents tooth cavity, earache, pain killer and prevents Tuberculosis.

Important phyto-chemicals and effects: In general, the plant is enriched with compounds known as glucosinolates and isothiocyanates, covalently linked to the sugar, rhamnose. The bark and stem synthesize two alkaloids Moringine and Moringinine. In addition to those,  more bio active compounds are also identified like, β – sitosterol, β – sitostenone, 4 – hydroxymellain, vanillin and octacosanic acid. β – Sitosterol works by competing with cholesterol during metabolic interaction and also contending with the steroid molecules toward their respective receptors. Therefore it is frequently used for numerous reasons like in preventing heart diseases and production of high cholesterol, immune boosting, preventing cancers of colon or cervices and other cancers, or gall stones, flu, rheumatoid arthritis, tuberculosis, psoriasis, allergies, lupus, asthma, bronchitis, enlarged prostate and many others. It is often used by the women for menopausal syndrome also even enhancing the sexual activity. β – Sitostenone displays some of the above activities but it has dominant role against tuberculosis. 4 – Hydroxy mellain has strong antifungal effect. Vanillin possesess sweet aroma and it is edible. So it is often used in the ice creams and confectioneries for pleasant aroma. The widely known, Glucosinolates and isothiocyanates play potent anti-tumor role. It is established that they induce apoptosis in varieties of cancer and tumor cells. They also have the properties like anti-inflammatory, estrogenic, anti-progestational, hypoglycemic, anti-ulcerative, anti-hyperthyroidism, hypocholesteremic, and hypotensive, anti-microbial, laxative and anti-spasmodic effects. The exudate or gum have large reserve of mono and polysaccharides, Arabinose, Galactose, and Glucuronic acid, Rhamnose, Mannose and Xylose. Flowers enriched with K and Ca bear high level of amino acids and proteins also containing numerous flavonoids and alkaloids. Compounds like thiocarbamates and isothiocyanates isolated from the seed-pods which have strong hypotensive property. The leaves are excellent source of antioxidants like ascorbic acid, flavonoids, carotenoids and poly-phenols. Besides the anti-oxidants, it has number of vitamins like A, B, C, K, pyridoxine, β – carotene and high extent of amino acids and proteins. All these components make Moringa leaves a good dietary complement. Regarding the seed oil, it has considerable amount of phytosterols like, Stigmasterol, β –sitosterol, Campesterol, Δ⁵– avenasterol and few others. Stigmasterol is considered as being a precursor of vitamin D₃. It also has the potential of preventing ovarian, prostate, breast and colon cancers. Campesterol has the ability to lower LDL and cholesterol. It can reduce atherogenic plaque. Cholesterol maintains cell membrane integrity, fluidity and mobility. It is the precursor of all steroid hormones, bile acid and vitamin D₃. The fatty composition of Moringa oil shows that it is enriched with oleic acid (68 – 76 %) along with the others. The oil is also noticed to be a good source of tocopherols, α, γ and δ.

Pharmacological properties: Reiterating the fact that each and every part of the Moringa Oleifera plant has potent medicinal role which is authenticated since the mentioning of early Ayurveda of ancient India. Below is the briefings of some of the acts.

Antihypertensive, Diuretic and cholesterol lowering actions – The unique combination of lipid lowering, blood pressure reducing and diuretic components in Moringa Oleifera makes it a useful natural drug for cardiovascular disorders. Glycosides of nitrile and thio-carbamate like Niazinin A & B, Niazimicin and Niazinin A + B are largely responsible for the lowering effect on blood pressure which is recorded from number of experiments. The effect is more pronounced in the case of seeds than compared to other parts of the plant and the possible action is mediated due to calcium antagonist behavior of the components. The carbamate and isothiocyanate which are seen abundant in the pods are liable also for the hypotensive role. Additionally, Methyl – p – benzoate and β – sitosterol in the pods also induce hypotensive effects. Interestingly, the diuretic property is noticed within all parts of the plant like roots, leaves, flowers, seeds and gums. It plays additional role in the lowering of blood pressure. The existence of β – sitosterol significantly lowers the level of serum cholesterol, phospholipids and tri-glycerides, low density lipoprotein and very low density lipoprotein which is verified from the number of experiments.

Antispasmodic, antiulcerative and hepatoprotective effect – The antispasmodic action of this plant occurs by the blockade of calcium channel owing to the presence of Moringine inside Moringa Oleifera roots or leaves which is effective against any common diarrheas. The flavonoids like quercitin and others within the plant offer strong hepatoprotective effect.

Anti-bacterial and antifungal effects – The roots show strong antibacterial action. The compound Pterygospermin produced inside the root exerts strong fungicidal effect. Besides Pterygospermin, Niazinin B and N-benzyl S – ethyl thioformate present in the stem bark and fresh leaf juice also show pronounced antibacterial and antifungal property especially against Staphylococcus aureus and Pseudomonas aeruginosa.

Anti-tumor and anti-cancer actions – The compounds, O – ethyl- 4 – (α – L- rhamnosyl) benzyl carbamate along with 4 (α – L – rhamnosyl) – benzyl isothiocyanate, Niazimicin and 3 – O – (6-oleol – β – D – glucopyranosyl) – β – sitosterol have potent antitumor property. They also showed considerable inhibitory action on Epstein Barr virus early antigen. Niazimicin shows potent chemopreventive action during chemical induced carcinogenesis. The seeds are effective on hepatic carcinogen metabolizing enzymes and antioxidant actions. The compound Niaziminin, thiocarbamte compound that exists in leaves shows inhibitory action on tumor promoter induced Epstein – Barr virus activation. The naturally occurring isothiocyanates in Moringa Oleifera also acts in similar way.

Miscellaneous other actions and uses – There are many diverse actions of this plant including those which are shown below.

• Extract from leaf can treat hyperthyroidism and also displays anti-oxidant effect.
• The leaf extract provides significant radiation protection toward bone marrow during radiation treatment.
• The extract of leaf is effective against Herpes Simplex Virus type -1 especially that are resistant toward Acyclovir.
• Water purification by crushed seed cake for its strong coagulating behavior.
• Antimicrobial actions of seed cake to flocculate both gram-positive and gram-negative bacteria.