Hwansodan protects PC12 cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein (MAP) kinase pathway

Hwansodan has been used as a prescription for senile and vascular dementia in Oriental medicine. We investigated the neuroprotective effects of Hwanso dan water extract on the apoptotic death of PC12 cells by serum deprivation . Hwansodan significantly rescued PC12 cells from apoptotic death by serum deprivation in a dose-dependent manner. The nuclear staining of PC12 cells clearly showed that Hwansodan attenuated nuclear condensation and fragmenta tion, which represents typical neuronal apoptotic characteristics. Hwansoda n also prevents DNA fragmentation and caspase-3-like protease activation in serum-deprived PC12 cells and induces the tyrosine phosphorylation of prot eins around 44 kDa, which was identified as ERK1 with electrophoretic gel m obility shift by Western blot. In addition, MER inhibitor PD98059 and Pas i nactivator, alpha -hydroxyfarnesylphosphonic acid and mevastatin, attenuate d the neuroprotective effects of Hwansodan in serum-deprived PC12 cells. Th ese results indicate that Ras/MEK/ERK signaling pathway plays a role in neu roprotective effects of Hwansodan in serum-deprived PC12 cells. (C) 2001 El sevier Science Inc. All rights reserved.