Cyanidin-3-O-glucoside ameliorates DSS-induced colitis in mice by modulating the PI3K-Akt pathway and preserving intestinal barrier function.

Anthocyanins, naturally occurring pigments in fruits and vegetables, have gained attention for their potential health benefits, including anti-inflammatory and gut-protective properties. In this study, we investigated the protective effects and underlying mechanisms of cyanidin-3-O-glucoside (C3G), a major dietary anthocyanin, in a dextran sulfate sodium (DSS)-induced murine model of inflammatory bowel disease (IBD). Oral administration of C3G significantly alleviated disease activity, attenuated body weight loss, reduced colon shortening, and suppressed systemic and colonic inflammation. C3G treatment restored intestinal barrier integrity by upregulating mucin 2 (MUC2) and key tight junction proteins, including occludin, claudin-1, and ZO-1. Integrated transcriptomic and network pharmacology analyses identified the PI3K-Akt signaling pathway and apoptosis as key targets of C3G. Experimental validation showed that C3G reduced TUNEL-positive cells in the colon and modulated apoptosis-related proteins by increasing Bcl-2 expression and decreasing cleaved caspase-3 levels. These findings indicate that C3G ameliorates experimental colitis, potentially through modulation of the PI3K-Akt pathway and suppression of epithelial apoptosis, supporting its potential as a functional food component for intestinal health.