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

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 A beta((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 A beta((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 A beta((1- 42))-induced cytotoxicity, in a concentration dependent manner. To investigate the compounds that could explain the observed effects, theW. 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 (c) 2010 John Wiley & Sons, Ltd.