Prota 11(1): Medicinal plants/Plantes médicinales 1
DC., Prodr. 13(1): 453 (1852).
2n = 48
Physalis flexuosa L. (1753).
Ashwagandha, winter cherry, Indian ginseng, poison gooseberry (En). Coqueret somnifère, poc-poc sauvage, ti-poc-poc (Fr). Erva moura sonífera, pontadeira, malagueta de galinha, uva caneça (Po). Mtemua shamba, mhulapori (Sw).
Origin and geographic distribution
The distribution area of Withania somnifera extends from the Canary Islands and the Mediterranean region through Africa, the Middle East, India and Sri Lanka to China. It also occurs in Australia. In Africa it occurs wild or naturalized throughout the drier parts of the continent including South Africa and in several Indian Ocean islands. Withania somnifera is of ancient use; it is mentioned in Ayurvedic literature as an important medicine, but it is difficult to ascertain whether the drug then described was Withania somnifera. It is mostly collected from wild stands, but in India it has been cultivated for centuries, mainly in Madhya Pradesh and Rajasthan.
Withania somnifera is more important as a drug plant in India than in Africa. In Ayurvedic medicine it has been used for centuries as a ‘rasayana’, a group of drugs that improve overall physical and mental health and increase longevity and vitality by rejuvenating the body. It is also considered narcotic, hypnotic, aphrodisiac, liver tonic, purgative and diuretic, and is used in the treatment of tuberculosis, senile debility, nervousness, rheumatism, furuncles, sores, dropsy, cough and hiccup, as well as to induce abortion. An ointment is made from the leaves that is applied to wounds and bed sores. It is an alternative for ginseng (Panax ginseng C.A.Mey.), but its mode of action is different. In India a plant extract is also applied to the skin as an antidote against cobra poison.
Although less popular than in India, Withania somnifera has many medicinal uses in Africa. In Cape Verde an infusion of the leaves is taken to purify the blood. Several preparations from the plant are diuretic and are used to cleanse the body of gonorrhoea. In Ethiopia the plant is used in the treatment of cough, asthma and epilepsy. In Somalia smoke of the burning plant is wafted over patients with slow blood circulation. The leaves or roots are pounded together with parts of other plants as an abortifacient. The leaves are given as a purgative and to treat general body pain. Ash of the leaves is rubbed in to treat ulcers and gingivitis. Leaves or decoctions of them are used to treat erysipelas and haemorrhoids. Leaf or root powder is boiled with fat and applied as an ointment on sores, abscesses or smallpox. Leaf sap is applied on anthrax pustules, and anthrax infected meat is boiled in water to which leaves are added. Leaf sap is used as ear drops to cure purulent otitis. Leaves or roots are also used in preparations to treat poorly healing open wounds. In Madagascar a plant infusion is used to treat asthma. In Mauritius a poultice made from the fresh leaves and roots is applied on rheumatic limbs. The plant is also used as a tonic, aphrodisiac and to treat skin problems.
Pounded roots or root powder are used in medicines against ringworm. Root powder mixed with milk is drunk as an aphrodisiac. A root decoction is drunk to treat dysuria, gonorrhoea or upset stomach, while a maceration of the roots is given as an enema against gangrenous inflammation of the rectum. A decoction of the root bark is drunk to treat asthma. Roots are used as an abortifacient, which seems to contradict their use in South Africa to enhance fertility in women with a history of miscarriages or the use in Somalia to regulate menses. In southern Africa the hypnotic effects of an alcoholic extract are used in the treatment of alcoholism, tuberculosis and emphysema. In Somalia a root decoction is given to children with fever and disturbed sleep, e.g. from nightmares; rubbing preparations of crushed leaves has similar effects. Roasted roots are placed around the house to repel snakes and scorpions.
In veterinary medicine in southern Africa, an ointment containing green fruits, stems and leaves is applied to wounds due to belts and saddles.
Leaves are sometimes eaten by goats and even by humans as a vegetable, but there are several reports that they are poisonous. The fruits are rich in saponins and can be used as a soap substitute; they also have an emetic effect. The seeds are used to curdle milk to make cheese. The leaves have insect repellent properties.
Production and international trade
The root of Withania somnifera is in great demand in the crude drug market. The annual requirement of the drug in the Indian market has been estimated at 9000 t (2004/2005). The current farm gate price for the roots in India stands at US$ 1.50 per kg.
Pharmaco-chemical analysis of Withania somnifera has revealed a very large number of bio-active compounds. Attention was first drawn to its alkaloids, including the piperidine and pyrrolidine alkaloids anaferine, anahygrine, isopelletierine and cuscohygrine, and the tropane-alkaloids pseudotropine and tropine and derivatives thereof. Currently, research attention focuses on ergostane-type steroidal lactones, the most important ones being withaferin A and a number of withanolides (especially withanolide E), witha-dienolides, withasomniferols and withanone, and on the related glycosides called sitoindosides and withanosides. A dimeric thiowithanolide, ashwagandhanolide, has been isolated from the roots.
In India an aqueous alcohol extract of the root called ‘ashwagandha’ is widely available as a commercial product. Extracts of various plant parts and their active compounds have a broad spectrum of pharmacological activities, and anti-oxidant effects or modulation of oxidative processes play a predominant role. Extensive research has been done on their effects on brain stimulation, heart disease, anxiety and stress, Parkinson’s disease, snake venom, inflammation, immunomodulation and especially cancer.
Withaferin A and sitoindosides VII-X given daily to rats increased the levels of the major free-radical scavenging enzymes (superoxide dismutase, catalase, glutathione peroxidase) in a dose dependent manner. An aqueous alcohol root extract showed positive cardioprotective effects in tests with rats. When studying the effect on the liver, a similar protective effect was found in the livers of rats treated with a toxic overdose of iron. The sitoindosides extracted from the roots showed significant antidepressant and anxiety-relieving properties in several rat models. In a test for chronic stress in rats, a root extract was compared with an extract from Panax ginseng; both extracts had a positive effect on several chronic stress symptoms, but the Withania somnifera extract did not cause the ginseng abuse syndrome, indicating a different mode of action. Cognition enhancing tests of an aqueous ethanol extract containing withaferin A and sitoindosides, studied in rat and mice models, showed a positive effect on cholinergic signal transduction in the forebrain, which may partly explain its cognition-enhancing effect. Mice injected with amyloid-β from plaques of Alzheimer’s patients showed less degeneration of memory and neurons when simultaneously injected with withanoside IV. Chronic administration of ashwagandha reversed reserpine-induced and scopolamine-induced memory deficits; the extract also had a consolidating effect on the memories of mice administered chronic convulsive electroshocks. Ashwagandha furthermore reversed or attenuated the catalepsy, tardive dyskinesia and toxic effects of 6-hydroxydopamine (6-OHDA), which may provide leads towards treatments for Parkinson’s disease. Aqueous alcohol extracts of the roots showed a positive effect on the cartilage of osteoarthritis patients both in vitro and in vivo in tests with rats.
The immunomodulatory effects of withanolides have been studied extensively. Enhanced white blood cell counts and activity and inhibition of delayed-type hypersensitivity are among the processes reported. In tests with mice treated with drugs that cause bone marrow damage, glyco-withanolides, including sitoindosides IX and X, caused increased counts of platelets and red and white blood cells and increased activity of peritoneal macrophages and lysosomal enzymes. Administration of ashwagandha also prevented suppression of macrophage motility and suppression of the production of interleukin-1 and tumour necrosis factor-α.
Aqueous root extracts fed to mice caused lower morbidity due to Bordetella pertussis, the causal agent of whooping cough, compared to the control animals. In another series of trials, intraperitoneal administration of the root extract to mice increased the white blood cell count, the number of bone marrow cells and antibody-forming cells. Delayed hypersensitivity was prevented in a Mantoux test.
The properties of root extracts of Withania somnifera are very promising in cancer therapy and several studies indicate that they are correlated with the antioxidant effects. The extracts not only affect tumour growth but also have positive adjuvant effects in radiation and chemo-therapy. In an in-vitro experiment, withaferin A inhibited growth in human cell lines of breast, central nervous system, colon and lung cancer. Another recent study found that a chloroform extract of ashwagandha prevented cell proliferation by disrupting mitosis and inhibiting angiogenesis in several models. The relation between the antioxidant properties of root extracts and cancer was shown in an experiment with mice with lung tumours induced by benzopyrene. The extract reinforced the action of the anti-cancer drug paclitaxel; in mice treated with benzopyrene and administered both the extract and paclitaxel, levels of ATPase activity were as low as in untreated control mice. Increased ATPase levels are an indication of oxidative stress associated e.g. with cancer. The radiosensitizing effect of the root extract and of withaferin A was confirmed in several studies, e.g. on fibrosarcoma tumours and on more radio-resistant melanoma tumours in mice. The aqueous alcohol root extract had a positive effect on the immune system of normal and tumour-bearing mice treated with mitogens. The extract enhanced the proliferation of spleen cells, lymphocytes, bone marrow cells and thymocytes in response to mitogens. The effects of aqueous leaf extracts on cancer cells have been investigated mainly in vitro. Cultured osteocarcinoma and breast cancer cells showed reduced proliferation and symptoms of senescence when treated with the extract. When the cells were exposed to high oxidative stress, they became more susceptible to oxidative damage after treatment with the leaf extract. Withanolides inhibit cyclooxygenase enzymes, lipid peroxidation and proliferation of tumour cells, acting through modulation of the activation of nuclear transcription factor kappa-B ( NF-κB) and NF-κB-regulated expression of genes that regulate cellular proliferation, carcinogenesis, metastasis and inflammation.
Addition of root powder to the diet of rats has shown hypoglycaemic effects in both normal and hyperglycaemic animals. A withanolide-free hydrosoluble fraction from the roots has been found to exhibit significant anti-stress activity in a dose-related manner in experiments with rats and mice. Although ashwagandha is used as an aphrodisiac, adding root powder to the diet of male rats impaired their libido and sexual performance. The methanolic extract of the roots showed significant antibacterial activity against a range of bacteria. Oral administration of the extract controlled Salmonella infection in mice. Stem bark extracts from Kenyan plants were tested for their activity against Plasmodium falcifarum, but the effect was minimal. When studying the anti-snake-venom properties of Withania somnifera, it was found that a glycoprotein isolated from an aqueous extract of the plant neutralized the toxic effects of phospholipase A2 from cobra venom. However, its mode of action may be too slow to provide a basis for pharmacological developments.
Side effects of the medicinal use of ashwagandha are rarely reported, but a case of thyrotoxicosis caused by its use was reported in the Netherlands. Symptoms disappeared when the treatment was stopped.
Evergreen, erect or spreading, rarely decumbent shrub 60–100(–200) cm tall; younger parts densely short stellate-hairy; roots stout, fleshy, pale brown; stem woody at base, profusely branched. Leaves alternate, upper ones usually nearly opposite, simple; stipules absent; petiole 0.5–3.5 cm long, sheathing at base; blade ovate to obovate, 2.5–17.5 cm × 1–7 cm, base slightly unequal, obtuse to cuneate, apex acute to obtuse, margins entire to sinuate, whitish stellate-hairy, later becoming sparsely hairy. Inflorescence an axillary cluster of 2–8 flowers. Flowers erect or nodding, bisexual, 5-merous, regular, yellowish to greenish white; pedicel 2–5 mm long, extending to 9 mm in fruit; calyx campanulate, tube 3–5.5 mm long, lobes triangular to nearly linear, 1–3 mm long, densely stellate-hairy; corolla campanulate to funnel-shaped, 5–8 mm long, hairy, lobes triangular, 2–2.5 mm long; stamens inserted near base of corolla and alternating with the lobes, scarcely exserted, filaments 2.5–3 mm long, anthers forming a cone around the style, up to 1 mm long; disk annular; ovary superior, ovoid, 1–2 mm × 0.5–1.5 mm, 2-celled, stigma head-shaped. Fruit a pendulous, globose berry 5–7 mm in diameter, orange to red, many-seeded, enclosed by persistent, membranous to papery calyx 10–24 mm × 8–17 mm, somewhat 5-angled, brownish. Seeds lens-shaped to kidney-shaped, 2–2.5 mm × 1.5–2 mm, orange, bright red or pale brown, reticulately wrinkled. Seedling with epigeal germination.
Other botanical information
Withania comprises about 10 species and is indigenous to the warm and temperate regions of the Old World. It is morphologically and chemically related to Physalis. Withania somnifera is the only species occurring in Africa. Cultivated plants in India differ from wild ones morphologically as well as in the amounts of the various chemical constituents present. They have been classified in a distinct species, Withania ashwagandha Kaul, but they are currently no longer considered a separate species.
Growth and development
Flowering occurs throughout the year. Flowers are self-fertile, but are also visited by bees.
Withania somnifera occurs on disturbed soil, along roadsides, in cultivated land, on termite mounds in grassland, in open woodland and riverine vegetation, from sea-level up to 2300 m altitude. It is grown in areas with 500–750 mm annual rainfall and prefers well-drained soil; waterlogging is harmful. It grows well in sandy loams and stony red clay soils with pH 7.5–8. It thrives in full sun, but tolerates some shade.
Propagation and planting
Withania somnifera is propagated by seed, either sown in a nursery or directly in the field. Traditional land preparation consists of several ploughings and planking to prepare a weed-free seedbed. When sown in a nursery, seeds are sown at the onset of the rains and the seed requirement is (0.5–)2–5 kg/ha. Treatment with a fungicide is recommended. Germination starts after 10–12 days. Seedlings are sufficiently tall after 25–30 days to be transplanted into the field, normally at a spacing of 60 cm × 60 cm. For direct sowing in the field, either in line or broadcasting, 5–10 kg seed per ha is needed. The sowing depth is 1–3 cm. When seedlings have 2–4 leaves they are thinned to a spacing of about 15 cm × 15 cm.
In India Withania somnifera is grown as an annual. One hand weeding at an early stage of the crop is often sufficient. Manure or fertilizer is rarely applied as it is believed to result in leafy plants with poor root quality, but in experiments, moderate applications of N (50 kg/ha) and P (25 kg/ha) increased yields to more than 800 kg/ha and gave thicker roots.
Diseases and pests
No serious diseases or pests have been reported. Damping off and root rot of young plants caused by Fusarium solani can be controlled by seed treatment or fungicide application.
In India cultivated plants start flowering in December and the crop is ready for harvesting in January–March, about 6 months after sowing when leaves start to wilt and fruits are ripe. Whole plants are uprooted and roots are cut from the plant about 2 cm above the collar. Fruits are picked by hand.
A good crop in India yields 650–800 kg/ha of fresh roots (350–450 kg/ha dry roots), but the average is 300–500 kg/ha. The average yield of seed is 50–75 kg/ha.
Handling after harvest
Roots are carefully cleaned, cut into 7–10 cm long pieces, dried and graded. Fruits are also dried and the seeds are removed by crushing the dry fruits.
Withania somnifera occurs naturally or has become naturalized in many parts of the tropics. Although it is nowhere common, it is unlikely to be liable to genetic erosion. The Regional Research Laboratory of the Indian Council of Agricultural Research (ICAR), Jammu Tawi, India maintains a collection of germplasm.
Several improved cultivars have been released in India, including ‘Rakshita’, ‘Poshita’, ‘WS-20’ and ‘WS-22’.
With the medicinal potential presented by Withania somnifera, the prospects for further exploitation look promising. Modern research confirms the activity of the drug, although the information has not yet resulted in registered drugs in mainstream medicine. The efficacy and relative safety of this plant, coupled with the ease of propagation, seem to warrant the planting of Withania somnifera for medicinal purposes. Nonetheless, the standardization of the drug ashwagandha needs to be effected so that it can be integrated in pharmacopeias.
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Sources of illustration
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Correct citation of this article:
Gurib-Fakim, A., 2008. Withania somnifera (L.) Dunal. In: Schmelzer, G.H. & Gurib-Fakim, A. (Editors). Prota 11(1): Medicinal plants/Plantes médicinales 1. [CD-Rom]. PROTA, Wageningen, Netherlands.
wild and naturalized
1, flowering and fruiting branch; 2, calyx, cut open to show fruit.
Redrawn and adapted by Iskak Syamsudin
obtained from B. Wursten
fruit in opened calyx
obtained from B. Wursten