2,6-dimethoxy-1,4-benzoquinone alleviates dextran sulfate sodium-induced ulcerative colitis in mice by suppressing NLRP3 inflammasome activation
LIU Chenfei
ZHANG Wei
ZENG Yao
LIANG Yan
WANG Mengting
ZHANG Mingfang
LI Xinyuan
WANG Fengchao
YANG Yanqing
Abstract：Objective To investigate the therapeutic mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ)for alleviating dextran sulfate sodium(DSS)-induced ulcerative colitis(UC)in mice.Methods Eighteen male C57BL/6J mice were equally randomized into control group,DSS group and DMQ treatment group.In DSS and DMQ groups,the mice were treated with DSS in drinking water to induce UC,and received intraperitoneal injections of sterile PBS or DMQ(20 mg/kg)during modeling.The changes in body weight,disease activity index(DAI),colon length,spleen weight,and colon histological scores of the mice were examined,and the percentages of Th17 and IFN-γ+CD8+T cells in the mesenteric lymph nodes and spleen were analyzed using flow cytometry.The expressions of tight junction proteins(Occludin and ZO-1),proteins associated with inflammasome activation(caspase-1 and p20),IL-1β and TNF-α in the colon tissues were detected using Western blotting or ELISA.In the cell experiment,mouse bone marrow-derived macrophages(BMDMs)primed with lipopolysaccharide(LPS)were treated with DMQ,followed by stmulation with nigericin to activate the classical NLRP3 inflammasome pathway.In cultured human peripheral blood mononuclear cells(PBMCs)treated with either LPS alone or LPS plus nigericin,the effects of DMQ on inflammasome activation,pyroptosis,and cytokine release were evaluated via Western blotting,ELISA,and flow cytometry.Results In DSS-treated mice,DMQ treatment significantly alleviated DSS-induced body weight loss,colon shortening,spleen enlargement,and colon inflammation.The DMQ-treated mice showed significantly reduced percentages of Th17 cells and IFN-γ+CD8+T cells in the mesenteric lymph nodes and spleen,with increased occludin and ZO-1 expressions and decreased caspase-1 expression in the colon tissue.DMQ obviously inhibited classical NLRP3 inflammasome activation in mouse BMDMs and both the classical and alternative pathways of NLRP3 activation in human PBMCs,causing also suppression of caspase-1-dependent pyroptosis.Conclusion DMQ ameliorates DSS-induced UC in mice by inhibiting NLRP3 inflammasome activation.
Keywords：26-dimethoxy-14-benzoquinoneNLRP3 inflammasomeulcerative colitisnatural products
Publication Date：2025-08-20
Online Publishing Date：2025-09-15(First online date of this platform, not the publication date of the document)
Pages：9( 1654-1662 )