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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:11

Enthalten in:

ACS chemical neuroscience - 11(2020), 10 vom: 20. Mai, Seite 1495-1503

Sprache:

Englisch

Beteiligte Personen:

Tong, Yue [VerfasserIn]
Fu, Huiling [VerfasserIn]
Xia, Changbo [VerfasserIn]
Song, Wen [VerfasserIn]
Li, Yuanjie [VerfasserIn]
Zhao, Jianjun [VerfasserIn]
Zhang, Xia [VerfasserIn]
Gao, Xiaojuan [VerfasserIn]
Yong, Jingjiao [VerfasserIn]
Liu, Quanxia [VerfasserIn]
Yang, Caiyan [VerfasserIn]
Wang, Hanqing [VerfasserIn]

Links:

Volltext

Themen:

APM8UQ3Z9O
Antidepressive Agents
Astragalin
Depression
EC 3.5.1.-
Inflammasomes
Journal Article
Kaempferols
NF-κB
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 inflammasome
Research Support, Non-U.S. Gov't
SIRT1
Sirtuin 1

Anmerkungen:

Date Completed 18.06.2021

Date Revised 18.06.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acschemneuro.0c00156

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM309482771