Astragalin Exerted Antidepressant-like Action through SIRT1 Signaling Modulated NLRP3 Inflammasome Deactivation

ACS Chem Neurosci. 2020 May 20;11(10):1495-1503. doi: 10.1021/acschemneuro.0c00156. Epub 2020 May 4.


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.

Keywords: Astragalin; Depression; NF-κB; NLRP3 inflammasome; SIRT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / pharmacology
  • Inflammasomes*
  • Kaempferols
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein*
  • Sirtuin 1


  • Antidepressive Agents
  • Inflammasomes
  • Kaempferols
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • astragalin
  • Sirtuin 1