Baicalin promotes hippocampal neurogenesis via the Wnt/β-catenin pathway in a chronic unpredictable mild stress-induced mouse model of depression

Hippocampal neurogenesis is known to be related to depressive symptoms. Increasing evidence indicates that Wnt/beta-catenin signaling regulates multiple aspects of adult hippocampal neurogenesis. Baicalin is a major flavonoid compound with multiple pharmacological effects such as anti-inflammatory, anti-apoptotic, and neuroprotective effects. The current study aimed to explore the antidepressant effects of baicalin and its possible molecular mechanisms affecting hippocampal neurogenesis via the regulation of the Wnt/beta-catenin signaling pathway. A chronic mild unpredictable stress (CUMS) model of depression was used in the study. The CUMS-induced mice were treated with baicalin (50 and 100 mg/kg) for 21 days, orally, and the fluoxetine was used as positive control drug. The results indicated that baicalin alleviated CUMS-induced depression-like behaviour, and improved the nerve cells' survival of the hippocampal dentate gyrus (DG) in CUMS-induced depression of model mice and increased Ki-67- and doublecortin (DCX)-positive cells to restore CUMS-induced suppression of hippocampal neurogenesis. The related proteins in the Wnt/beta-catenin signaling pathway, which declined in the CUMS-induced depression model of mice, were upregulated after baicalin treatment, including Wingless3a (Wnt3a), dishevelled2 (DVL2), and beta-catenin. Further study found that the phosphorylation rate of glycogen synthase kinase-3 beta (GSK3 beta) and beta-catenin nuclear translocation increased, as the levels of the beta-catenin target genes cyclinD1, c-myc, NeuroD1, and Ngn2 upregulated after baicalin treatment. In conclusion, these findings suggest that baicalin may promote hippocampal neurogenesis, thereby exerting the antidepressant effect via regulation of the Wnt/beta-catenin signaling pathway.

Automated summary

Baicalin may promote hippocampal neurogenesis and alleviate depression-like behaviors induced by chronic mild unpredictable stress through regulation of the Wnt/beta-catenin signaling pathway.