Withania: Background. Actions

2010

Common Name

Withania

Other Names

Ashwagandha (and a variety of spellings including ashvagandha, ashwaganda, asvagandha), Ayurvedic ginseng, Indian ginseng, winter cherry

Botanical Name / Family

Withania somnifera (family Solanaceae)

Sometimes confused with Physalis alkekengi, also known as winter cherry.

Plant Parts Used

Primarily root, although berry, leaves and bark are sometimes used.

Chemical Components

Steroidal lactones (withanolides, withaferin A), alkaloids (including withanine, somniferine, isopelietierine, anaferine, tropine, pseudotropine), flavonoids, saponins, sitoindosides, iron, choline, acylsteryl glucosides, coumarins (scopoletin and aesculetin), triterpene (beta-amyrin), phytosterols (stigmasterol and beta-sitosterol), essential oils (ipuranol, withaniol).

Historical Note

The name ashwagandha (one of the common names for this herb) comes from the Sanskrit meaning ‘horse-like smell’. Apparently, this name not only refers to the smell of the herb but also its strengthening and aphrodisiac qualities. It is often referred to as ‘Indian ginseng‘ because it is used in much the same way in Ayurvedic medicine as Panaxginseng in TCM, although it is considered less stimulating.

Withania:  Main Actions

ADAPTOGEN (MODULATES STRESS RESPONSES)

Withania has been shown to attenuate the negative effects of chronic stress in rats, including hyperglycaemia, glucose intolerance, increase in plasma corticosteroid levels, gastric ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and mental depression. Animal trials have shown that a withanolide-free hydrosoluble fraction of withania reduces the stress response induced both chemically and physically. It suppresses stress-induced increases in dopamine receptors in the corpus striatum and acts as a GABA-mimetic agent by binding to GABA receptors. Animal studies also suggest an ability to reduce adrenal weight and plasma cortisol levels, thus potentially protecting against the negative effects of elevated cortisol levels in chronic stress and allostasis.

NERVOUS SYSTEM ACTIVITY

Cognitive enhancement

Memory enhancement has been confirmed by animal studies and appears to be mediated by a cholinergic. Increased cortical muscarinic acetylcholine receptor capacity has been observed in animals and humans with extracts of withania. Several withanolides exert calcium antagonistic ability, together with anticholinesterase activity, by inhibiting butyrylcholinesterase and acetylcholinesterase enzymes. The presence of choline in the herb may also contribute to the production of acetylcholine and further increase cholinergic effects.

Neuroprotective

Several animal studies indicate the potential for protection of neurons, including protection from neuronal injury in Parkinson’s disease and promotion of dendrite formation. One possible explanation is due to the antioxidant properties of withania.

In animal models of haloperidol-induced dyskinesia (chewing movements, tongue protrusion and buccal tremors), the reported benefits of withania appear to be due to its antioxidant rather than GABA-mimetic action. In vitro results suggest that withanolide A is able to reconstruct neuronal networks, including axons, dendrites, pre- and postsynapses, in the neurons.

ANTIOXIDANT

Withania exerts an indirect antioxidant action in vivo. Daily administration of Withania somnifera root extract increases hepatic glucose-6-phosphatase activity and decreases hepatic lipid peroxidation, most likely by increasing the activity of endogenous antioxidant enzymes. In vitro Withania somnifera inhibits both the lipid peroxidation and the protein oxidative modification induced by copper. In animal studies the antioxidant actions have been proposed as a possible mechanism for withania preventing the negative effects of stroke induced by middle cerebral artery occlusion.

INCREASES HAEMATOPOIESIS

Animal trials indicate the herb increases haemoglobin and red blood cell levels and increases haematopoiesis. The iron content of the herb may further contribute to its role in red blood cell formation.

IMMUNOMODULA TION

Animal studies have shown immunomodulating effects of withania, including an increase in white blood cell, platelet and neutrophil counts, increases in IFN-gamma and IL-2 and a reduction in TNF. In vitro, increased nitric oxide production by macrophages has also been reported. Withaferin A and withanolide D may cause immunosuppression, but other factors have immunostimulant effects.

ANTIBACTERIAL AND ANTIFUNGAL ACTIVITY

Animal and in vitro studies have shown antibacterial effects against Staphylococcus aureus, Listeria monocytogenes, Bacillus anthracis, Bacillus subtilis, Salmonella enteridis and Salmonella typhimurium. The methanol and hexane extracts of both the leaves and the roots have potent antibacterial activity against S. typhimurium and Escherichia coli; and the steroidal withanolides from the related species W. coagulens have been found to have antifungal activity against Allescheria boydii, Aspergillus niger, Curvularia lunata, Drechslera rostrata, Epidermophyton floccosum, Microsporum canis, Nigrospora oryzae, Pleurotus ostreatus and Stachybotrys atra.

ANTI-INFLAMMATORY ACTIVITY

The withanolides (steroidal lactones) are considered to have anti-inflammatory effects. Several withanolides exert selective COX-2 enzyme inhibition and withania has been found to decrease alpha-2-macroglobulin, a liver-synthesised plasma protein that increases during inflammation. A reduction in the erythrocyte sedimentation rate has also been noted in a double-blind clinical trial of 50-59 year old males.

ANTICANCER (ANTINEOPLASTIC AND CHEMOPREVENTION)

Studies show that withania can stimulate the production of cytotoxic T-lymphocytes in vivo and in vitro, and that it may prevent or reduce tumour growth. Withania was found in animal models to prevent skin carcinoma induced by UVB radiation and forestomach tumours; reduce the incidence, number and size of tumours; and to counteract the associated decrease in body weight.

Thewithaferin A fraction appears to exert anti-angiogenic activity and may be partly responsible for the antineoplastic effects observed in vitro and in vivo studies. The antioxidant effects aid in the prevention of DNA damage by mutagens and this in combination with detoxifying properties, anti-inflammatory and immunomodulatory effects, determined in animal studies, are likely to contribute to its chemopreventive action.

ANXIOLYTIC AND ANTIDEPRESSANT

Animal studies have found glycowithanolides to exert anxiolytic effects comparable to those of lorazepam, and antidepressant effects comparable to those of the antidepressant drug, imipramine.

Withania:  Other Actions

CARDIOPROTECTIVE

Cardioprotective effects have been noted in animal studies, significantly reducing myocardial injury after ischaemia and reperfusion. The alkaloids are considered to be sedative and reduce blood pressure and heart rate. The withanolides have a chemical structure similar to cardiac glycosides and have demonstrated mild ionotropic and chronotropic effects on the heart.

THYROID MODULATING

An in vivo study reported that daily administration of Withania somnifera root extract enhanced serum T4 concentration.

SEXUAL ENHANCER

Traditionally used for this purpose, one double-blind clinical trial found that a dose of 3 g taken daily for 1 year improved the sexual performance of 71.4% of healthy ageing males. Alternatively, animal studies have indicated that very high doses (3000 mg/kg) result in reduced sexual performance.

HEPATOPROTECTIVE

Animal studies have demonstrated hepatoprotective effects and that withania inhibits phase I, and activates phase II and antioxidant enzymes in the liver.