Puerarin inhibits expression of macrophage NLRP3 inflammasome to alleviate ulcerative colitis and preliminary analysis of its mechanism
10.3969/j.issn.1000-484X.2025.04.002
- VernacularTitle:葛根素抑制巨噬细胞NLRP3炎症小体表达减轻溃疡性结肠炎及其初步机制分析
- Author:
Xin ZHAO
1
;
Xutao CHEN
;
Xingyu LU
;
Wenli DAN
;
Guojun GAO
;
Kang TANG
;
Lihua CHEN
Author Information
1. 陕西中医药大学医学技术学院,咸阳 712046;空军军医大学基础医学院免疫学教研室,西安 710032
- Publication Type:Journal Article
- Keywords:
Ulcerative colitis;
Puerarin;
Macrophage;
NLRP3 inflammasome
- From:
Chinese Journal of Immunology
2025;41(4):775-782
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of natural plant compound puerarin(PUE)on expression of NLRP3 inflamma-some in macrophages and its effect in ulcerative colitis(UC)in mice.Methods:A mouse model of UC was established using dextran sulfate sodium(DSS).Mice received PUE via gavage for 7 consecutive days,body weight,disease activity index and colon length were measured.HE staining was performed to assess tissue pathological damage.Flow cytometry was used to determine the proportion of peripheral blood mononuclear cells in colonic lamina propria.Immunofluorescence was employed to assess the colocalization of NLRP3 inflammasome and macrophages.qRT-PCR was conducted to measure mRNA expression levels of pro-inflammatory cytokines and NLRP3-related genes in colonic tissues.Protein expression levels of ZO-1,Occludin,cleaved caspase-1 and IL-1β in colonic tissues were detected by Western blot.A cell model was established using lipopolysaccharide(LPS)and adenosine triphosphate(ATP).mRNA expression levels of genes related to NLRP3 inflammasome were detected by qRT-PCR.Western blot was used to detect effects of PUE on expression levels of proteins related to NLRP3 inflammasome and NF-κB signaling pathway.Results:PUE treatment signifi-cantly improved symptoms of DSS-induced UC in mice,including body weight,disease index,colon length and pathological damage.Following PUE intervention,infiltration of Ly6C+MHC Ⅱ-monocyte derived macrophages in the colonic lamina propria was reduced.Expression levels of pro-inflammatory cytokines and NLRP3 inflammasome related molecules in colonic tissues were decreased.PUE treatment increased expression levels of ZO-1 and Occludin in intestinal epithelial cells.In vitro experiments confirmed that PUE reduced expression levels of NLRP3 inflammasome-related molecules in macrophages induced by LPS combined with ATP,as well as protein expression level of p-NF-κB p65.Conclusion:PUE significantly alleviates the symptoms of UC by reducing intestinal tissue inflamma-tion and repairing the epithelial barrier.The mechanism may involve regulating NF-κB signaling pathway,thereby reducing the forma-tion and activation of NLRP3 inflammasome in macrophages.
