Fisetin protects against rotenone-induced neurotoxicity through signaling pathway.

The present study was designed to evaluate the protective effect of fisetin against rotenone induced toxicity in SH-SY5Y neuroblastoma cellular model of Parkinson's disease (PD). SH-SY5Y neuroblastoma cells were treated with fisetin (5µM) 2 hr prior to being treated with rotenone (100 nM). Following the exposure of SH-SY5Y cells to rotenone, there was marked decreased cell viability, increased oxidative stress, activation of caspase-3 and apoptosis (dual staining, expressions of pro-apoptotic and anti-apoptotic indices). However pretreatment with fisetin significantly and dose-dependently alleviated rotenone induced cytotoxicity and oxidative stress in SH-SY5Y cells. Moreover, fisetin attenuated rotenone induced toxicity by down-regulating Bax, caspases-3 protein expression and up-regulating protein expression of Bcl-2, p38/JNK-MAPK and PI3K, Akt, GSK-3β pathways. Collectively, these results suggest that fisetin could prevent the rotenone-induced neurotoxicity via various signaling pathways.