南方医科大学学报2025，Vol.45Issue(11)：2483-2494,12.DOI:10.12122/j.issn.1673-4254.2025.11.21
珠子草素通过调控p38/JNK信号通路抑制肠上皮细胞凋亡保护肠屏障改善克罗恩病样肠炎
Niranthin ameliorates Crohn's disease-like enteritis in mice by inhibiting intestinal epithelial cell apoptosis and protecting intestinal barrier via modulating p38/JNK signaling
摘要
Abstract
Objective To investigate the therapeutic effect of the natural compound niranthin on Crohn's disease-like colitis in mice and explore the underlying molecular mechanisms.Methods In a mouse model of colitis induced by 2,4,6-trinitro-benzenesulfonic acid(TNBS),the therapeutic effect of niranthin was evaluated by observing the changes in body weight,disease activity index(DAI),and colon length of the mice.The levels of inflammatory cytokines(IL-6,IL-1β,TNF-α,IL-17A and IL-10)in the intestinal mucosal tissue were detected using ELISA and quantitative real-time PCR(qRT-PCR).TUNEL staining and Western blotting were used to assess intestinal epithelial cell apoptosis and the expressions of Bcl-2 and Bax.The expression levels of tight junction proteins(ZO-1 and claudin-1)and the activation of the p38/JNK signaling pathway were investigated using Western blotting,and diprovocim intervention experiments were conducted to explore the molecular regulatory mechanism of niranthin.Results Niranthin treatment significantly increased body weight of TNBS-treated mice,lowered the DAI and histological inflammation scores,and increased colon length of the mice.The niranthin-treated mouse models showed obviously reduced protein and mRNA levels of IL-6,IL-1β,IL-17A,and TNF-α and upregulated expression of IL-10 in the colon tissue.TUNEL staining and Western blotting demonstrated that niranthin significantly inhibited intestinal epithelial cell apoptosis and activated the anti-apoptotic pathway in the mouse models.Niranthin treatment obviously upregulated the expression levels of ZO-1 and claudin-1 and downregulated the phosphorylation levels of p38 and JNK in the colon tissues of the mice.Diprovocim intervention obviously attenuated the inactivation of the p38/JNK signaling pathway induced by niranthin in the mouse models.Conclusion Niranthin ameliorates TNBS-induced Crohn's disease-like colitis in mice by inhibiting intestinal epithelial cell apoptosis and protecting the integrity of the intestinal barrier via regulating the activation of the p38/JNK signaling pathway.关键词
克罗恩病/炎症性肠病/肠上皮细胞凋亡/p38/JNK/珠子草素Key words
Crohn's disease/inflammatory bowel disease/intestinal epithelial cell apoptosis/p38/JNK/Niranthin引用本文复制引用
陶露,陈悦,黄林林,郑旺,宋雪,项平,胡建国..珠子草素通过调控p38/JNK信号通路抑制肠上皮细胞凋亡保护肠屏障改善克罗恩病样肠炎[J].南方医科大学学报,2025,45(11):2483-2494,12.基金项目
安徽省卫生健康委科研项目(AHWJ2024Aa40007) （AHWJ2024Aa40007）
安徽省临床医学研究转化专项(202427b10020093) （202427b10020093）
安徽省重点实验室开放课题(YZ2024D06) （YZ2024D06）
安徽省高校科学研究项目(2023AH040289) （2023AH040289）
