title: 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 H(2)O(2)- 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 H(2)O(2)- 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 H(2)O(2)- 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.
authors.affiliation: Medicinal Plant Research Group, School of Agriculture, Food and Rural Development, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: C J
authors.initials: CJ
authors.lastname: Seal
authors.forename: M J R
authors.initials: MJ
authors.lastname: Howes
authors.forename: G C
authors.initials: GC
authors.lastname: Kite
authors.forename: E J
authors.initials: EJ
authors.lastname: Okello
mesh_terms: D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D002470:Cell Survival; D006861:Hydrogen Peroxide / Q000009:adverse effects*; D008515:Medicine, Ayurvedic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000009:adverse effects*; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D032341:Withania / Q000737:chemistry*; D054358:Withanolides / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D054358:Withanolides; C075222:amyloid beta-protein (1-42); D006861:Hydrogen Peroxide; C009684:withaferin A