SIRT1/FOXO1 Axis-Mediated Hippocampal Angiogenesis is Involved in the Antidepressant Effect of Chaihu Shugan San

作者：Shan Zhang, Yujia Lu, Wei Shi, Yi Ren, Kaihui Xiao, Wei Chen, Li Li, Jingjie Zhao · 发表于：Drug Design Development and Therapy · 年份：2022 · DOI：10.2147/dddt.s370825 · 被引用次数：25 · 研究领域：Tryptophan and brain disorders、Sirtuins and Resveratrol in Medicine、FOXO transcription factor regulation

Objective: Chaihu Shugan San (CSS) has a long history for treating major depressive disorder (MDD), which has been verified effectively and safely in clinical studies. Deficient angiogenesis plays important roles in MDD. However, the underlying mechanisms of CSS on angiogenesis remain poorly understood. Methods: Network pharmacology analysis was applied to explore the potential angiogenic targets and pathways between CSS and MDD. These targets would be validated in chronic unpredictable mild stress (CUMS)-induced depressive-like mice by Western blots, immunofluorescence, and immunohistochemistry. Then, the underlying molecular mechanisms were further investigated in brain microvascular endothelial cells (BMVECs) with CSS-containing serum by Western blots and immunofluorescence. Results: Network pharmacology analysis showed that the antidepressant role of CSS was closely associated with Silent information regulator protein 1 (SIRT1)/Forkhead box O1 (FOXO1) axis-mediated angiogenesis. This prediction was confirmed in the following experiments. CSS induced angiogenesis, increased SIRT1 expression, and decreased FOXO1 expression in the hippocampus of CUMS mice. Five percent CSS-containing serum produced a significant increase in BMVECs proliferation, migration, and tube formation, but these effects were reduced by SIRT1 silencing. CSS serum could also promote FOXO1 translocation to the cytoplasm through SIRT1 signaling, which triggered FOXO1 protein degradation. What is more, CSS...