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Astragalin Exerted Antidepressant-like Action through SIRT1 Signaling Modulated NLRP3 Inflammasome Deactivation.
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-05-04 , DOI: 10.1021/acschemneuro.0c00156 Yue Tong 1 , Huiling Fu 2 , Changbo Xia 1 , Wen Song 1 , Yuanjie Li 1 , Jianjun Zhao 1 , Xia Zhang 1 , Xiaojuan Gao 1 , Jingjiao Yong 1 , Quanxia Liu 3 , Caiyan Yang 2 , Hanqing Wang 1, 4, 5
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2020-05-04 , DOI: 10.1021/acschemneuro.0c00156 Yue Tong 1 , Huiling Fu 2 , Changbo Xia 1 , Wen Song 1 , Yuanjie Li 1 , Jianjun Zhao 1 , Xia Zhang 1 , Xiaojuan Gao 1 , Jingjiao Yong 1 , Quanxia Liu 3 , Caiyan Yang 2 , Hanqing Wang 1, 4, 5
Affiliation
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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.
中文翻译：
通过SIRT1信号调节的NLRP3炎性体失活，黄芪素发挥了抗抑郁样作用。
炎症在抑郁症和抗抑郁疗法的发病机理中起着关键作用。黄芪素（AST）是一种具有抗炎特性的生物活性类黄酮。但是，尚未解决黄芪抗抑郁药的作用。在这项研究中，我们探讨了黄芪素的抗抑郁作用及其潜在机制。我们的结果表明，AST可以显着改善慢性不可预测轻度应激（CUMS）模型中的行为缺陷，促进SIRT1表达，并降低NF-κBp65，NLRP3，裂解的capase-1，裂解的IL-1β和裂解的胃泌素D的蛋白质水平。在海马中。免疫组织化学显示AST减轻了CUMS诱导的小胶质细胞过度活化。在体外，AST可以显着提高脂多糖（LPS）和三磷酸腺苷（ATP）处理的BV2细胞的细胞活力，SIRT1表达上调，而核NF-κBp65，NLRP3，裂解的capase-1和裂解的胃泌素D的蛋白水平下调。在免疫细胞化学中AST给药后观察到裂解的Gasdermin D裂解下降。但是，SIRT1抑制剂EX-527损害了AST的体内和体外作用。这些结果表明，AST具有抗抑郁特性，这取决于SIRT1信号调节的NLRP3炎性体失活。
更新日期：2020-05-04
中文翻译：
通过SIRT1信号调节的NLRP3炎性体失活，黄芪素发挥了抗抑郁样作用。
炎症在抑郁症和抗抑郁疗法的发病机理中起着关键作用。黄芪素（AST）是一种具有抗炎特性的生物活性类黄酮。但是，尚未解决黄芪抗抑郁药的作用。在这项研究中，我们探讨了黄芪素的抗抑郁作用及其潜在机制。我们的结果表明，AST可以显着改善慢性不可预测轻度应激（CUMS）模型中的行为缺陷，促进SIRT1表达，并降低NF-κBp65，NLRP3，裂解的capase-1，裂解的IL-1β和裂解的胃泌素D的蛋白质水平。在海马中。免疫组织化学显示AST减轻了CUMS诱导的小胶质细胞过度活化。在体外，AST可以显着提高脂多糖（LPS）和三磷酸腺苷（ATP）处理的BV2细胞的细胞活力，SIRT1表达上调，而核NF-κBp65，NLRP3，裂解的capase-1和裂解的胃泌素D的蛋白水平下调。在免疫细胞化学中AST给药后观察到裂解的Gasdermin D裂解下降。但是，SIRT1抑制剂EX-527损害了AST的体内和体外作用。这些结果表明，AST具有抗抑郁特性，这取决于SIRT1信号调节的NLRP3炎性体失活。
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