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Withania somnifera

About: Withania somnifera is a research topic. Over the lifetime, 2116 publications have been published within this topic receiving 43404 citations. The topic is also known as: Ashwaganda & Indian ginseng.


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Journal ArticleDOI
TL;DR: Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20‐methylcholanthrene injected mice, which may be due to its antioxidant and detoxifying properties.
Abstract: The current experimental work deals with the chemopreventive studies of a hydroalcoholic extract of Withania somnifera roots, against 20-methylcholanthrene induced fibrosarcoma tumours in Swiss albino mice. A single subcutaneous injection of 200 microg 20-methylcholanthrene in 0.1 mL of dimethylsulphoxide into the thigh region of mice produced a high incidence (96%) of tumours. Oral treatment of animals with 400 mg/kg body weight of Withania somnifera extract (one week before injecting 20-methylcholanthrene and continued until 15 weeks thereafter) significantly reduced the tumour incidence, tumour volume and enhanced the survival of the mice, compared with 20-methylcholanthrene injected mice. The tumour incidence was also delayed in the treatment group when compared with 20-methylcholanthrene injected mice. Liver biochemical parameters revealed a significant modulation of reduced glutathione, lipid peroxides, glutathione-S-transferase, catalase and superoxide dismutase in extract treated mice compared with 20-methylcholanthrene injected mice. The mechanism of chemopreventive activity of Withania somnifera extract may be due to its antioxidant and detoxifying properties.

101 citations

Journal ArticleDOI
04 Sep 2012-PLOS ONE
TL;DR: It is demonstrated that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells, and Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells.
Abstract: Background and Purpose: Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library. Methodology/Principal Findings: In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails.

101 citations

Journal ArticleDOI
TL;DR: A total of two new and four known withanolides were isolated from the whole plant of Withania somnifera and only compounds 3, 4, and 6 were found to be active against acetylcholinesterase.
Abstract: A total of two new (1, 2) and four known (3-6) withanolides were isolated from the whole plant of Withania somnifera. Their structures were elucidated on the basis of spectroscopic techniques and were characterized as 6alpha,7alpha-epoxy-3beta,5alpha,20beta-trihydroxy-1-oxowitha-24-enolide (1), 5beta,6beta-epoxy-4beta,17alpha,27-trihydroxy-1-oxowitha-2,24-dienolide (2), withaferin-A (3), 2,3-dihydrowithaferin-A (4), 6alpha,7alpha-epoxy-5alpha,20beta-dihydroxy-1-oxowitha-2,24-dienolide (5), and 5beta,6beta-epoxy-4beta-hydroxy-1-oxowitha-2,14,24-trienolide (6), respectively. Compounds 2, 3, 5, and 6 displayed inhibitory potential against butyrylcholinesterase, but only compounds 3, 4, and 6 were found to be active against acetylcholinesterase.

101 citations

Journal ArticleDOI
TL;DR: Ashwagandha (Withania somnifera Dunal., Solanaceae) is one of the most reputed medicinal plants of Ayurveda, the traditional medical system and its specific secondary metabolites known as withanolides, the novel group of ergostane skeletal phytosteroids named after the plant, are studied.
Abstract: Ashwagandha (Withania somnifera Dunal., Solanaceae) is one of the most reputed medicinal plants of Ayurveda, the traditional medical system. Several of its traditionally proclaimed medicinal properties have been corroborated by recent molecular pharmacological investigations and have been shown to be associated with its specific secondary metabolites known as withanolides, the novel group of ergostane skeletal phytosteroids named after the plant. Withanolides are structurally distinct from tropane/nortropane alkaloids (usually found in Solanaceae plants) and are produced only by a few genera within Solanaceae. W. somnifera contains many structurally diverse withanolides in its leaves as well as roots. To date, there has been little biosynthetic or metabolism-related research on withanolides. It is thought that withanolides are synthesized in leaves and transported to roots like the tropane alkaloids, a group of bioactive secondary metabolites in Solanaceae members known to be synthesized in roots and transported to leaves for storage. To examine this, we have studied incorporation of (14)C from [2-(14)C]-acetate and [U-(14)C]-glucose into withanolide A in the in vitro cultured normal roots as well as native/orphan roots of W. somnifera. Analysis of products by thin layer chromatography revealed that these primary metabolites were incorporated into withanolide A, demonstrating that root-contained withanolide A is de novo synthesized within roots from primary isoprenogenic precursors. Therefore, withanolides are synthesized in different parts of the plant (through operation of the complete metabolic pathway) rather than imported.

100 citations

Journal ArticleDOI
TL;DR: Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models, and key in vivo preclinical studies demonstrating anticancer effects of WA are summarized.
Abstract: The plants used in Ayurvedic medicine, which has been practiced in India for thousands of years for the treatment of a variety of disorders, are rich in chemicals potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is one such medicinal plant whose anticancer value was realized over four decades ago after isolation of a crystalline steroidal compound (withaferin A) from the leaves of this shrub. The root and leaf extracts of W. somnifera are shown to confer protection against chemically-induced cancers in experimental rodents, and retard tumor xenograft growth in athymic mice. Anticancer effect of W. somnifera is generally attributable to steroidal lactones collectively referred to as withanolides. Withaferin A (WA) appears most active against cancer among structurally divergent withanolides isolated from the root or leaf of W. somnifera. Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models. This review summarizes the key in vivo preclinical studies demonstrating anticancer effects of WA. Molecular targets and mechanisms likely contributing to the anticancer effects of WA are also discussed. Finally, challenges in clinical development of WA for the prevention and treatment of cancer are highlighted.

99 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023114
2022265
202188
2020124
201995
2018111