Ardisiacrispin B, a natural triterpenoid saponins, suppresses dextran sulfate sodium-induced inflammatory bowel disease by rebalancing the gut microbiota and Th17/Treg of mice.

Abstract

Ardisiacrispin B (AB) has demonstrated anti-inflammatory and anti-tumor activities, yet its therapeutic potential in inflammatory bowel disease (IBD) remains unexplored. This study evaluated the efficacy of AB in dextran sulfate sodium (DSS)-induced IBD in mice by monitoring body weight, disease activity index, stool consistency, rectal bleeding, and colon length. Intestinal barrier integrity and inflammatory responses were assessed via ELISA, FITC-dextran permeability, Western blot, and immunohistochemistry. Gut microbiota composition was profiled using 16S rRNA sequencing, along with bioinformatics to predict potential mechanisms, which were subsequently validated through immunofluorescence and flow cytometry. The results showed that AB significantly mitigated body weight loss, DAI scores, colon length shortening, and splenomegaly in mice, and alleviated the pathological damage to the colon. AB strengthened intestinal barrier integrity by increasing ZO-1, Occludin, claudin-1, MUC2, and EPO levels, and reducing ET-1 and DAO levels. AB suppressed inflammation by reducing IL-1β, IL-6, and TNF-α levels, and inhibiting JAK2/STAT3 and TLR4/MyD88/NF-κB pathways. Additionally, AB rebalanced the gut microbiota by increasing beneficial bacteria (Akkermansia) and decreasing pathogenic bacteria (Bacteroides and Helicobacter). Interestingly, AB rebalanced Th17/Treg by decreasing the colonic IL-17 level, increasing IL-10, IL-22, and TGF-β levels, and reversing the proportion of Th17/Treg cells in the blood, mesenteric lymph nodes, and spleen of IBD mice. These findings demonstrate that AB mitigates DSS-induced IBD through coordinated regulation of intestinal barrier integrity, gut microbiota composition, and Th17/Treg immune balance, identifying AB as a promising candidate for IBD therapy.