OBJECTIVE To investigate the effects of coptisine on endogenous metabolites in a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model, and to explore its potential mechanisms of action employing non-targeted metabolomics technology.

METHODS SPF-grade male C57BL/6 mice were randomly divided into a control group, a model group, a sulfasalazine group (100 mg·kg^-1), and low and high dose groups of coptisine groups (25, 50 mg·kg^-1). To induce ulcerative colitis (UC), all groups except the control group had free access to a 2.5% DSS solution for 7 days. At the same time, they also received daily intragastric administration of their corresponding treatments until the 10th day. Body weight changes, stool characteristics, and bloody stool occurrence were recorded daily, and the disease activity index (DAI) was calculated. After the experiment, colon tissues were collected for pathological examination. Through UPLC-Q-TOF-MS/MS, non-targeted metabolomic analysis was performed to identify differential metabolites, and metabolic pathway enrichment analysis was conducted using the KEGG database.

RESULTS Compared to the model group, coptisine significantly ameliorated weight loss, DAI scores, and pathological damage in colon tissues of UC mice (P < 0.05, P < 0.01). Metabolomic analysis identified 56 differential metabolites, mainly involved in purine metabolism, tryptophan metabolism, niacin and nicotinamide metabolism, glutathione metabolism, and the biosynthesis of phenylalanine, tyrosine, and tryptophan. Coptisine intervention significantly reversed the abnormal expression of these metabolites.

CONCLUSION Coptisine can markedly improve metabolic disorders in DSS-induced UC mice by modulating multiple key metabolic pathways, thereby exerting a therapeutic effect.