1Department of Neurology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
2Department of Emergency Internal Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
3Laboratory of Neurology, Institute of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
4Department of Integrative Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
5Center for Translational Neurodegeneration and Regenerative Therapy, Shanghai Tenth People’s Hospital Affiliated with Tongji University School of Medicine, Shanghai 200072, China
6Department of Immunology, Tongji University School of Medicine, Shanghai 200092, China

Abstract 

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.

Keywords

Echinacoside; Parkinson’s disease; 1-Methyl-4-phenylpyridinium ion; Reactive oxygen species; ATF3; CHOP

[SpringerLink]