Trilobatin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice via the NF-κB pathway and alterations in gut microbiota

Author:

Wang Nanbo,Li Zhaohui,Cao Lingling,Cui ZhihuaORCID

Abstract

Objective This study aimed to evaluate the effects of trilobatin (TLB) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and further explore the underlying mechanisms from the perspectives of signaling pathway and gut microbiota. Methods A mouse model of UC was established using DSS. Trilobatin was administered via oral gavage. Disease severity was assessed based on body weight, disease activity index (DAI), colon length, histological detection, inflammation markers, and colonic mucosal barrier damage. Alternations in the NF-κB and PI3K/Akt pathways were detected by marker proteins. High-throughput 16S rRNA sequencing was performed to investigate the gut microbiota of mice. Results In the DSS-induced UC mice, TLB (30 μg/g) treatment significantly increased the body weight, reduced the DAI score, alleviated colon length shortening, improved histopathological changes in colon tissue, inhibited the secretion and expression of inflammation factors (TNF-α, IL-1β, and IL-6), and increased the expression of tight-junction proteins (ZO-1 and occludin). Furthermore, TLB (30 μg/g) treatment significantly suppressed the activation of NF-κB pathway and altered the composition and diversity of the gut microbiota, as observed in the variations of the relative abundances of Proteobacteria, Actinobacteriota, and Bacteroidota, in UC mice. Conclusion TLB effectively alleviates DSS-induced UC in mice. Regulation of the NF-κB pathway and gut microbiota contributes to TLB-mediated therapeutic effects. Our study not only identified a novel drug candidate for the treatment of UC, but also enhanced our understanding of the biological functions of TLB.

Funder

Jilin Province Health Talent Special Project

Technology Capacity Enhancement Program of Health Commission of Jilin Province

National College Students Innovation and Entrepreneurship Training Program

Publisher

Public Library of Science (PLoS)

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