Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Province Academy of Chinese Medicine Sciences, Shijiazhuang 050031, China.
Neuroscience Research Center, Hebei Medical University, Shijiazhuang 050017, China.
Biochem Pharmacol. 2021 Aug;190:114594. doi: 10.1016/j.bcp.2021.114594. Epub 2021 May 6.
Hippocampal neurogenesis is known to be related to depressive symptoms. Increasing evidence indicates that Wnt/β-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/β-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/β-catenin signaling pathway, which declined in the CUMS-induced depression model of mice, were upregulated after baicalin treatment, including Wingless3a (Wnt3a), dishevelled2 (DVL2), and β-catenin. Further study found that the phosphorylation rate of glycogen synthase kinase-3β (GSK3β) and β-catenin nuclear translocation increased, as the levels of the β-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/β-catenin signaling pathway.
海马神经发生与抑郁症状有关。越来越多的证据表明，Wnt/β-catenin 信号通路调节成年海马神经发生的多个方面。黄芩素是一种主要的黄酮类化合物，具有多种药理作用，如抗炎、抗凋亡和神经保护作用。本研究旨在探讨黄芩素的抗抑郁作用及其通过调节 Wnt/β-catenin 信号通路影响海马神经发生的可能分子机制。采用慢性轻度不可预测应激（CUMS）抑郁模型进行研究。将 CUMS 诱导的小鼠用黄芩素（50 和 100mg/kg）灌胃处理 21 天，氟西汀作为阳性对照药物。结果表明，黄芩素减轻了 CUMS 诱导的抑郁样行为，改善了 CUMS 诱导的抑郁模型小鼠海马齿状回（DG）神经细胞的存活，并增加了 Ki-67 和双皮质素（DCX）阳性细胞，以恢复 CUMS 诱导的海马神经发生抑制。黄芩素处理后，上调了 Wnt/β-catenin 信号通路中下降的相关蛋白，包括 Wingless3a（Wnt3a）、dishevelled2（DVL2）和 β-catenin。进一步的研究发现，磷酸化糖原合成酶激酶-3β（GSK3β）和 β-catenin 核转位的比率增加，β-catenin 靶基因 cyclinD1、c-myc、NeuroD1 和 Ngn2 的水平上调。综上所述，这些发现表明，黄芩素可能通过调节 Wnt/β-catenin 信号通路促进海马神经发生，从而发挥抗抑郁作用。
