Senkyunolide A protects corticosterone-induced cell apoptosis via modulating protein phosphatase 2A and α-synuclein Running title: Neuroprotective effects of Senkyunolide A

Dan-zhi-xiao-yao-san is a Traditional Chinese Medicine (TCM) formula that is widely used to treat depression related neurological disorders, however, the active compound(s) and underlying mechanisms are unclear. In the present study, we found that senkyunolide A (SenA) has neuroprotective effects in corticosterone (Cort)-induced depression cell model in PC12 cells. Firstly, we found that SenA protects Cort-induced cell injury in PC12 cells. In addition, SenA attenuates Cort-induced the reduction of phosphatase 2A (PP2A) activities, and the increase of p-PP2A, α-syn and p-α-syn-Ser129 levels. Furthermore, PP2A inhibitor okadaic acid (OA) decreased, and PP2A activator D-erythro-Sphingosine (SPH) increased Cort-induced cell apoptosis. Importantly, we also found that the neuroprotective effects of SenA in Cort-induced cell injury via modulating α-syn levels. Collectively, our results suggest that the neuroprotective effects of SenA in Cort-induced depression cell model via modulating PP2A activities and α-syn levels, and bring a breakthrough to the anti-depression mechanisms for natural compound SenA.