Neuroprotective Effect of Dioscin against Parkinson's Disease via Adjusting Dual-Specificity Phosphatase 6 (DUSP6)-Mediated Oxidative Stress

Exploration of lead compounds against Parkinson's disease (PD), a neurodegenerative disease, is of great important. Dioscin, a bioactive natural product, shows various pharmacological effects. However, the activities and mechanisms of dioscin against PD have not been well investigated. In this study, the tests on 6-hydroxydopamine (6-OHDA)-induced PC12 cells and rats were carried out. The results showed that dioscin dramatically improved cell viability, decreased Reactive Oxygen Species (ROS) levels, improved motor behavior and tyrosine hydroxylase(TH) levels and restored the levels of glutathione (GSH) and malondialdehyde (MDA) in rats. Mechanism investigation showed that dioscin not only markedly increased the expression level of dual- specificity Phosphatase 6 (DUSP6) by 1.87-fold in cells and 2.56-fold in rats, and decreased phospho-extracellular regulated protein kinases (p-ERK) level by 2.12-fold in cells and 2.34-fold in rats, but also increased the levels of nuclear factor erythroid2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), superoxide dismutase (SOD) and decreased the levels of kelch-1ike ECH-associated protein l (Keap1) in vitro and in vivo. Furthermore, DUSP6 siRNA transfection experiment in PC12 cells validated the protective effects of dioscin against PD via regulating DUSP6 to adjust the Keap1/Nrf2 pathway. Our data supported that dioscin has protection against PD in regulating oxidative stress via DUSP6 signal, which should be considered as an efficient candidate for the treatment of PD in the future.