Schisandrin B shows neuroprotective effect in 6-OHDA-induced Parkinson’s disease via inhibiting the negative modulation of miR-34a on Nrf2 pathway

BackgroundMiR-34 family members have been previously shown to play potential functional role in Parkinson’s disease (PD) pathogenesis. However, the regulatory role of miR-34a has not been demonstrated in PD yet. This study aims to clarify the potential neuroprotective effect of Schisandrin B (Sch B) involving miR-34a function in 6-OHDA-induced PD model.MethodsThe expression changes of miR-34a and Nrf2 pathway related genes were detected in 6-OHDA-treated SH-SY5Y cells under Sch B pretreatment. Cell viability and PD feathers of 6-OHDA-induced PD mice were measured for neuroprotection assessment. The regulation of miR-34a on Nrf2 activity and expression was demonstrated through gain-of-function and loss-of-function studies, while the regulatory role of miR-34a in the neuroprotection of Sch B was investigated both in vitro and in vivo.ResultsSch B pretreatment ameliorated 6-OHDA-induced changes in vitro, like upregulated miR-34a expression, inhibited Nrf2 pathways and decreased cell survival, and PD feathers in vivo. Moreover, Nrf2 was negatively regulated by miR-34a, while miR-34a overexpression inhibited the neuroprotection of Sch B in both dopaminergic SH-SY5Y cells and PD mice.ConclusionSch B showed neuroprotective effect in 6-OHDA-induced PD pathogenesis, which could be inhibited by miR-34a, involving the negative regulatory mechanism of miR-34a on Nrf2 pathways.