Echinacoside Protects Against MPP(+)-Induced Neuronal Apoptosis via ROS/ATF3/CHOP Pathway Regulation

Echinacoside (ECH) is protective in a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenylpyridinium ion (MPP(+)). To investigate the mechanisms involved, SH-SY5Y neuroblastoma cells were treated with MPP(+) or a combination of MPP(+) and ECH, and the expression of ATF3 (activating transcription factor 3), CHOP (C/EBP-homologous protein), SCNA (synuclein alpha), and GDNF (glial cell line-derived neurotrophic factor) was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP(+)-induced reactive oxygen species (ROS). In addition, ECH suppressed the ROS and MPP(+)-induced expression of apoptotic genes (ATF3, CHOP, and SCNA). ECH markedly decreased the MPP(+)-induced caspase-3 activity in a dose-dependent manner. ATF3-knockdown also decreased the CHOP and cleaved caspase-3 levels and inhibited the apoptosis induced by MPP(+). Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP(+). ECH also improved dopaminergic neuron survival during MPP(+) treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP(+)-induced apoptosis in PD.