Objective To investigate the therapeutic effect of Qingchang Huazhuo Formula (QCHZF) on mice with ulcerative colitis (UC) and the influences of fecal metabolites based on non-targeted metabolomics to investigate the mechanism of action of QCHZF in the treatment of UC.

Methods UC mice were induced by dextran sulfate sodium salt (DSS) and were administered with QCHZF. During the experiment, the body weight, stool characteristics and blood in stool were recorded daily, and the disease activity index (DAI) was calculated. At the end of the experiment, the length of colon was measured, colonic tissue damage in mice were observed by hematoxylin-eosin and alcian blue staining, mRNA expression levels of inflammatory factors, IL-6, IL-18 and IL-1β, and intestinal barrier factors, ZO-1 and Muc2, were detected in colon tissues via qPCR method, and protein expression level of intestinal barrier, Muc2, was detected with immunofluorescence. Fecal metabolite changes in mice were detected employing un-targeted metabolomics and analyzed by MetaboAnalyst 5.0 for metabolic pathway enrichment.

RESULTS QCHZF significantly alleviated colitis symptoms, increased body weight, decreased DAI score, reversed colonic shortening, inhibited inflammatory factors expression, improved colonic tissue structure disorders, increased the number of goblet cells, and restored the intestinal barrier in UC mice, regulated 58 metabolites, mainly involving pathways of methionine and cysteine metabolism, purine metabolism, steroid hormone biosynthesis, vitamin B6 metabolism, tryptophan metabolism and primary bile acid pathways.

CONCLUSION QCHZF can improve colitis symptoms, repaire the intestinal barrier and modulate fecal metabolites and related metabolic pathways in UC mice.