Changyanning Granule alleviates DSS-induced ulcerative colitis in mice by regulating gut microbiota, MAPK pathway and intestinal epithelial barrier

Objective Changyanning Granule (CYNG) is a classic Chinese patent medicine that treats gastrointestinal disorders; however, its mechanism of action is unclear.This study investigated the protective effect of CYNG on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice and explored its mechanisms of action. Methods A mouse colitis model was established using 3% DSS. Disease activity was assessed by disease activity index (DAI). Histopathological changes were evaluated by hematoxylin-eosin (HE) and Alcian Blue-periodic acid-Schiff (AB-PAS) staining. Intestinal barrier function and inflammation were examined via immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), oxidative stress assays, reverse transcription polymerase chain reaction (RT-qPCR), and Western blotting (WB). Gut microbiota composition, short-chain fatty acid (SCFA) levels, and fecal metabolomic profiles were analyzed by 16S rRNA sequencing, targeted SCFA detection, and metabolomics, respectively. Results CYNG treatment significantly alleviated the symptoms of colitis, as evidenced by a decrease in DAI, and it also improved the colonic pathological damage in UC mice induced by DSS. Moreover, CYNG effectively restored the intestinal barrier function and alleviated colonic inflammation. Mechanistically, CYNG regulated the mitogen-activated protein kinase (MAPK) pathway by inhibiting the expression of p-p38 and p-JNK proteins. Furthermore, CYNG exerted protective effects by maintaining intestinal flora homeostasis, modulating SCFA and regulating amino acid metabolic. Conclusions CYNG effectively ameliorates DSS-induced ulcerative colitis via a synergistic mechanism involving the regulation of MAPK inflammatory signaling, gut microbiota and related metabolic disorders. These findings support the treatment of UC with CYNG.