南方医科大学学报2025，Vol.45Issue(3)：595-602,8.DOI:10.12122/j.issn.1673-4254.2025.03.17
升麻素抑制MAPK通路调节辅助性T细胞免疫平衡改善小鼠克罗恩病样结肠炎
Cimifugin ameliorates Crohn's disease-like colitis in mice by modulating Th-cell immune balance via inhibiting the MAPK pathway
摘要
Abstract
Objective To investigate the therapeutic effects of cimifugin on Crohn's disease(CD)-like colitis in mice and its possible mechanism.Methods Thirty adult male C57BL/6 mice were randomized equally into control group,2,4,6-trinitrobenzenesulfonic acid(TNBS)-induced CD-like colitis model group,and cimifugin treatment(daily gavage at 12.5 mg/kg)group.The therapeutic effect of cimifugin was evaluated by observing changes in body weight,disease activity index(DAI)scores,colon length,histopathological inflammation scores,and inflammatory cytokine levels in the colonic mucosa.Intestinal barrier integrity in the mice was assessed using immunofluorescence assay and Western blotting for claudin-1 and ZO-1;T-helper(Th)cell subset ratios in the mesenteric lymph nodes were analyzed with flow cytometry.Network pharmacology,KEGG enrichment analysis and molecular docking were used to predict the targets of cimifugin and analyze the key pathways and cimifugin-MAPK protein interactions,which were validated by Western blotting in the mouse models.Results In mice with TNBS-induced colitis,cimifugin treatment significantly attenuated body weight loss and colon shortening,lowered DAI and histopathological scores,decreased IFN-γ and IL-17 levels,and increased IL-4 and IL-10 levels in the colonic mucosa.Cimifugin treatment also significantly improved TNBS-induced claudin-1 dislocation and reduction of goblet cells,upregulated claudin-1 and ZO-1 expressions,reduced Th1 and Th17 cell percentages,and increased Th2 and Treg cell percentages in the colonic mucosa of the mice.KEGG analysis suggested a possible connection between the effect of cimifugin and MAPK signaling,and molecular docking showed strong binding affinity between cimifugin and MAPK core proteins.Western blotting demonstrated significantly decreased phosphorylation levels of JNK,ERK,and p38 in the colonic mucosa of cimifugin-treated mouse models.Conclusion Cimifugin alleviates TNBS-induced CD-like colitis by repairing intestinal barrier damage and restoring Th1/Th2 and Th17/Treg balance via suppressing MAPK pathway activation.关键词
克罗恩病/升麻素/MAPK/辅助性T细胞/免疫平衡/肠屏障Key words
Crohn's disease/cimifugin/MAPK/helper T cells/immune homeostasis/intestinal barrier引用本文复制引用
殷丽霞,牛民主,张可妮,耿志军,胡建国,李江艳,李静..升麻素抑制MAPK通路调节辅助性T细胞免疫平衡改善小鼠克罗恩病样结肠炎[J].南方医科大学学报,2025,45(3):595-602,8.基金项目
国家自然科学基金(81902078) （81902078）
安徽省高校优秀青年基金(2022AH030138) （2022AH030138）
安徽省卫生健康委科研项目(AHWJ2022b088) （AHWJ2022b088）
安徽省教育厅优秀青年教师培育项目(YQYB2023019) Supported by National Natural Science Foundation of China(81902078). （YQYB2023019）
