炎症体
黄芪甲素
药理学
抗抑郁药
化学
炎症
医学
内科学
海马体
生物化学
类黄酮
山奈酚
抗氧化剂
作者
Yue Tong,Huiling Fu,Changbo Xia,Wen Song,Yuanjie Li,Jianjun Zhao,Xia Zhang,Xiaojuan Gao,Jingjiao Yong,Quanxia Liu,Cai-Yan Yang,Hanqing Wang
标识
DOI:10.1021/acschemneuro.0c00156
摘要
Inflammation plays a key role in the pathogenesis of depression and antidepressant therapies. Astragalin (AST) is a bioactive flavonoid that possesses an anti-inflammatory property. However, the antidepressant action of astragalin has not been addressed. In this study, we explored the antidepressant effects of astragalin and its underlying mechanism. Our results showed that AST significantly improved the behavioral defects in chronic unpredictable mild stress (CUMS) model, promoted SIRT1 expression, and decreased the protein levels of NF-κB p65, NLRP3, cleaved capase-1, cleaved IL-1β and cleaved gasdermin D in the hippocampus. Immunohistochemistry revealed AST mitigated CUMS-induced microglia overactivation. In vitro, AST profoundly increased the cell viability in lipopolysaccharides (LPS) and adenosine triphosphate (ATP) treated BV2 cells, with upregulated SIRT1 expression and downregulated protein levels of nuclear NF-κB p65, NLRP3, cleaved capase-1, and cleaved gasdermin D. Declined cleavage of gasdermin D was observed after AST administration in immunocytochemistry. Nevertheless, the in vivo and in vitro effects of AST were compromised by SIRT1 inhibitor EX-527. These results indicated that AST possessed an antidepressant property, which was dependent on SIRT1 signaling modulated NLRP3 inflammasome deactivation.
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