Berberine improves colon damage of ulcerative colitis colonic epithelium by activating TAS2R38 signaling pathway.

Abstract

BACKGROUND: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease. Current treatment options have limitations in terms of efficacy and side effects. TAS2R38 is an important bitter taste receptor, and recent studies have suggested its potential role in gut immune regulation. This study aims to explore the role of the TAS2R38 receptor in UC and evaluate its potential as a therapeutic target. METHODS: A 3% DSS solution was used to induce colitis in mice. The expression of TAS2R38 and its downstream signaling pathway was assessed using immunohistochemistry, Western blot, and immunofluorescence. Through molecular docking and pharmacological screening, bitter compounds, that bind to TAS2R38 were identified. The therapeutic effects of bitter compounds on DSS-induced colitis were evaluated by monitoring body weight, measuring colon length, conducting HE staining, and assessing the mucus layer integrity. RESULTS: In the DSS-induced colitis mouse model, the TAS2R38 signaling pathway was found to be inhibited, particularly with a significant reduction in the expression of the downstream proteins PLCβ2 and IP3R3. Pharmacological screening and molecular dynamics simulations revealed that berberine strongly binds to TAS2R38 and effectively prevents DSS-induced colitis by activating this receptor. Berberine treatment significantly alleviated symptoms such as weight loss, diarrhea, and fecal occult blood, and improved colon length, spleen weight, and disease activity index (DAI). Additionally, HE staining showed that berberine significantly reduced DSS-induced epithelial damage and restored intestinal mucus barrier integrity. CONCLUSION: This study suggests that the TAS2R38 receptor may play a key role in the pathogenesis of ulcerative colitis. Berberine, by activating the TAS2R38 signaling pathway, exerts significant protective effects in DSS-induced colitis. TAS2R38 could be a potential therapeutic target for UC, and berberine, as a traditional Chinese medicine component, holds promise as a treatment for UC.