Protective Effect Of Physcion Against Corticosterone-induced Neurotoxicity To PC12 Cells By Modulation Of BDNF-TrkB Pathway

ObjectiveTo explore the effect of physcion on Corticosterone-induced neurotoxicity in PC12 cells via BDNF-TrkB pathway,in order to provide experimental evidence for the treatment of depression with Physcion.MethodsTaking PC12 cells as the subject investigated.Using Corticosterone-induced damge as the vitro model to simulate high concentration of Cort damage depression patient’s brain.Culture PC12 cells in vitro,treated with different concentrations of Corticosterone according to the groups.Then,inflicting Physcion to interfere.Finally,treatment of cells with BDNF-TrkB protein pathway blockers.The cytotoxicity of Corticosterone-induced PC12 cells and cell viability after injured by corticosterone were detected by cell counting Kit（CCK-8）;The protein content determined by ELISA;UV spectrophotometry was used to test the endogenous H₂S content and CBS activity in PC12 cells.The Percentage of apoptosis in PC12 cells detected by flow cytometry（FCM）.The level of Intracellular ROS was checked by DCFH-DA assay.The MFI of MMP was gauged under confocal laser microscopy after JC-1 dyed.Result1.Compared with Control group,Cort has neurotoxic effect on PC12 cells（P<0.01）;VS Cort-treated alone group,Physcion could reduce the inhibitory effect of corticosterone on PC12 activity（P<0.01）;VS Cort and Physcion co-treated group,K252a can reverse the protecing ability of Physcion on the survival rate of PC12cells（P<0.01）.Compared with Control group,Cort inhibits the normal expression of CBS in PC12 cells（P<0.01）.Compared with Control group,Cort can reduce the content of endogenous H₂S in cells（P<0.01）.2.Compared with Control group,The percentage of apoptosis significantly increased after Cort injured（P<0.01）;VS Cort-treated alone group,Physcion can observably antagonize corticosterone induced apoptosis（P<0.01）;VS Cort and Physcion co-treated group,K252a can reverse the effect of Physcion on the apoptosis of PC12 cells（P<0.01）.3.Compared with Control group,Cort can evidently increase the accumulation of ROS in PC12 cells（P<0.01）;VS Cort-treated alone group,Physcion can decrease the accumulation of endogenous ROS after corticosterone injury（P<0.01）;VS Cort and Physcion co-treated group,K252a can counteract the antioxidant effects of Physcion（P<0.01）.4.Compared with Control group,Physcion enhanced the expression of BDNF in PC12 cells in a dose gradient manner（P<0.01）,Cort certainly decreased the level of BDNF in cells（P<0.01）;VS Cort-treated alone group,Physcion could remarkably improve the inhibitory effect of Cort on BDNF expression（P<0.01）.5.Compared with Control group,Cort causeed the loss of cell MMP（P<0.01）;VS Cort-treated alone group,Physcion markedly relieved the phenomenon of MMP losing（P<0.01）;K252a can antagonize the role of Physcion in maintaining MMP（P<0.01）.Conclusion1.Physcion has protective effect on PC12 cells.2.BDNF-TrkB pathway mediates the protective effect of emodin on PC12 cells.