Baicalin Coadministration with Lithium Chloride Enhanced Neurogenesis via GSK3 beta Pathway in Corticosterone Induced PC-12 Cells

Accumulating studies suggest that hippocampal neurogenesis plays a crucial role in the pathological mechanism of depression. As a classic antidepressant, lithium chloride can play an antidepressant role by inhibiting glycogen synthase kinase 3 beta (GSK3 beta) and promoting neurogenesis. Correspondingly, baicalin is a compound extracted from natural plants, which shows potential antidepressant effect, however, whether baicalin exerts antidepressant effects by promoting neurogenesis still needs further investigation. In the current study, we established an in vitro depression model through corticosterone induced PC-12 cells, and explored the potential mechanism of baicalin's antidepressant effect by comparing it with lithium chloride alone and the coadministration with lithium chloride. We used Cell Counting Kit-8 (CCK-8) assay, 5-ethynil-2'-deoxyuridine (EdU) staining and cell cycle analysis to evaluate the state of cell survival and cell proliferation. The protein expression levels of neurodevelopmental related factors Doublecortin (DCX), brain-derived neurotrophic factor (BDNF), and the GSK3 beta pathway-related proteins and mRNA were detected by Western blot and Real-time PCR. The results showed that baicalin could decrease the expression level of GSK3 beta, while upregulate the expression level of DCX, BDNF, Cyclin D1-cyclin dependent kinase 4/6 (CDK4/6), thus promoted cell proliferation and survival in corticosterone (CORT) induced PC-12 cells. Moreover, this effect was enhanced when baicalin and lithium chloride were coadministration. Taking the above results together, we conclude that baicalin can promote the proliferation and development of PC-12 cells by regulating GSK3 beta pathway, so as to reverse the depressive-like pathological changes induced by corticosterone.