Abstract

INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation in the colon. Maintaining intestinal mucosal barrier integrity is a fundamental therapeutic objective in managing UC. Swertiamarin (STM) exhibits diverse biological activities and holds promise for the treatment of UC. Autophagy is a critical mechanism that safeguards the integrity of the intestinal mucosal barrier, yet it remains uncertain whether STM ameliorates UC and modulates autophagy to preserve this barrier. METHODS An acute colitis mouse model was induced by administering dextran sulfate sodium (DSS) in drinking water. The protective effects of different concentrations of STM against colitis were evaluated by monitoring body weight changes, disease activity index (DAI), colon length, spleen index, histological score, and AB-PAS staining. Colonic inflammation severity was assessed using ELISA and qPCR, while intestinal permeability was evaluated through FITC-dextran permeability assays, Western blotting, and immunohistochemistry. Caco-2/HIEC-6 cell monolayers were treated with 2% DSS, and the effects of STM on cellular inflammation and barrier function were assessed using Western blotting, qPCR, and a FITC-dextran permeability assay. Potential mechanisms and targets of STM for alleviating UC through intestinal epithelial cells were predicted using online databases and network pharmacology analysis. These predictions were subsequently validated through Western blotting. To elucidate the roles of autophagy and the PI3K/AKT/mTOR pathway in STM's protective effects, functional rescue experiments were conducted. These experiments utilized the autophagy inhibitor 3-methyladenine (3-MA) and the PI3K-specific agonist 740YP. Autophagic structures were directly visualized by transmission electron microscopy (TEM). RESULTS