Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring. In recent years, numerous pharmacological investigations have been carried out into the components of W. somnifera extracts. We present here an overview of the chemical structures of triterpenoid components and their biological activity, focusing on two novel activities, tumor inhibition and antiangiogenic properties of withaferin A and the effects of withanolide A on Alzheimer's disease. The most recent attempts in biotechnological production of withanolides are also discussed.

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Steroidal lactones from Withania somnifera, an ancient plant for novel medicine.

Herbal medicine for depression, anxiety and insomnia: A review of psychopharmacology and clinical evidence

Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders.

Withania somnifera, popularly known as Ashwagandha is widely considered as the Indian ginseng. In Ayurveda, it is classified as a rasayana (rejuvenation) and expected to promote physical and mental health, rejuvenate the body in debilitated conditions and increase longevity. Having wide range of activity, it is used to treat almost all disorders that affect the human health. The present review discusses the pharmacological basis of the use of W. somnifera in various central nervous system (CNS) disorders, particularly its indication in epilepsy, stress and neurodegenerative diseases such as Parkinson's and Alzheimer's disorders, tardive dyskinesia, cerebral ischemia, and even in the management of drug addiction.

Withania somnifera: an Indian ginseng.

Purpose: Ashwagandha is regarded as a wonder shrub of India and is commonly used in Ayurvedic medicine and health tonics that claim its variety of health-promoting effects. Surprisingly, these claims are not well supported by adequate studies, and the molecular mechanisms of its action remain largely unexplored to date. We undertook a study to identify and characterize the antitumor activity of the leaf extract of ashwagandha. Experimental Design: Selective tumor-inhibitory activity of the leaf extract (i-Extract) was identified by in vivo tumor formation assays in nude mice and by in vitro growth assays of normal and human transformed cells. To investigate the cellular targets of i-Extract, we adopted a gene silencing approach using a selected small hairpin RNA library and found that p53 is required for the killing activity of i-Extract. Results: By molecular analysis of p53 function in normal and a variety of tumor cells, we found that it is selectively activated in tumor cells, causing either their growth arrest or apoptosis. By fractionation, purification, and structural analysis of the i-Extract constituents, we have identified its p53-activating tumor-inhibiting factor as withanone. Conclusion: We provide the first molecular evidence that the leaf extract of ashwagandha selectively kills tumor cells and, thus, is a natural source for safe anticancer medicine.

https://clincancerres.aacrjournals.org/content/clincanres/13/7/2298.full.pdf

Selective killing of cancer cells by leaf extract of Ashwagandha: identification of a tumor-inhibitory factor and the first molecular insights to its effect.

Withania somnifera (WS) Dunal is classified in Ayurveda, the ancient Hindu system of medicine, as a rasayana, a group of plant-derived drugs reputed to promote physical and mental health, augment resistance of the body against disease and diverse adverse environmental factors, revitalise the body in debilitated conditions and increase longevity. These attributes are remarkably similar to the properties ascribed to adaptogens like Panax ginseng (PG) in contemporary medicine. As such, the adaptogenic activity of a standardised extract of WS roots was investigated against a rat model of chronic stress (CS). The stress procedure was mild, unpredictable footshock, administered once daily for 21 days to adult male Wistar rats. CS induced significant hyperglycaemia, glucose intolerance, increase in plasma corticosterone levels, gastric ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and mental depression. These CS induced perturbations were attenuated by WS (25 and 50 mg/kg po) and by PG (100 mg/kg po), administered 1 h before footshock for 21 days. The results indicate that WS, like PG, has significant antistress adaptogenic activity, confirming the clinical use of the plant in Ayurveda.

A.V Muruganandam

Papers

Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress