In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and β‐amyloid_(1–42)‐induced cytotoxicity in differentiated PC12 cells

Abstract

Withania somnifera L. Dunal (Solanaceae), also known as ‘ashwagandha’ in Sanskrit and as ‘Indian ginseng’, is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer, with antiaging, antistress, immunomodulatory and antioxidant properties. There is a paucity of data on the potential neuroprotective effects of W. somnifera root, as traditionally used, against H2O2‐ and Aβ(1–42)‐induced cytotoxicity which are current targets for novel approaches to treat dementia, especially dementia of the Alzheimer's type (AD). In this study, an aqueous extract prepared from the dried roots of W. somnifera was assessed for potential protective effects against H2O2‐ and Aβ(1–42)‐aggregated fibril cytotoxicity by an MTT assay using a differentiated rat pheochromocytoma PC12 cell line. The results suggest that pretreatments of differentiated PC12 cells with aqueous extracts of W. somnifera root significantly protect differentiated PC12 cells against both H2O2‐ and Aβ(1–42)‐induced cytotoxicity, in a concentration dependent manner. To investigate the compounds that could explain the observed effects, the W. somnifera extract was analysed by liquid chromatography–serial mass spectrometry and numerous withanolide derivatives, including withaferin A, were detected. These results demonstrate the neuroprotective properties of an aqueous extract of W. somnifera root and may provide some explanation for the putative ethnopharmacological uses of W. somnifera for cognitive and other neurodegenerative disorders that are associated with oxidative stress. Copyright © 2010 John Wiley & Sons, Ltd.

Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors

“…Overall all the peaks observed between 12 to 30 min are withanolide derivatives. The high abundances of withanolides derivatives are consistent with results from other studies (Kumar et al, 2010;Bolleddula et al, 2012). A comprehensive identification of all of the withanolide derivatives is not possible because to our knowledge no databases are available for MS/MS spectra and structures.…”

Effects of Withania somnifera on oral ethanol self-administration in rats

“…This possibility originates from the observation that several studies point (i) to the brain catalase-H 2 O 2 enzymatic system as a suitable pathway that oxidizes ethanol into acetaldehyde (Aragon et al, 1991;Aragon and Amit, 1992) and (ii) to the actions of acetaldehyde itself, of ethanol-derived acetaldehyde (Correa et al, 2012;Peana and Acquas, 2013), as well as of the product of condensation between dopamine and acetaldehyde, salsolinol (Melis et al, 2013), on dopamine neurons in the VTA as responsible for the reinforcing properties of ethanol (Rodd et al, 2008;Hipólito et al, 2011). Thus, on the basis of the observation that W. somnifera has long been suggested to exert its neuroprotective properties by acting as a free radical scavenger (Bhattacharya et al, 2001) and as an antihydrogen peroxide-mediated mechanism (Kumar et al, 2010), it appears reasonable to hypothesize that WSE may also interfere with the motivational effects of ethanol that require the involvement of central catalase activity (Font et al, 2008;Melis et al, 2013;.…”

Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice

“…WA induces apoptosis in cancer cells and potentiates the effects of other chemotherapeutic agents by activating tumor suppressor proteins and inducing oxidative stress [28–33]. On the other hand, WA also has anti-oxidant activity [10, 13–15, 34–36]. In this study, we tested the hypothesis that anti-oxidant effects of WA will reduce oxidative stress-induced liver injury.…”