Cyanidin-3-O-glucoside Alleviates Inflammatory Bowel Disease by Targeting the NF-κB Pathway and is Associated With...

Inflammatory bowel disease (IBD) is characterized by immune dysregulation and an imbalance in the gut microbiota. Cyanidin-3-O-glucoside (C3G), a natural anthocyanin with anti-inflammatory properties, shows therapeutic potential, though its mechanisms remain incompletely defined. This study evaluated the effects of C3G on intestinal inflammation, microbiota, metabolites, and nuclear factor-κB (NF-κB) signaling in a dextran sulfate sodium (DSS)-induced colitis model in BALB/c mice. In vitro RAW264.7 cells were used to assess pathway involvement. Molecular and histological analyses were performed using qRT-PCR, Western blotting, and immunostaining, while microbiota and metabolite profiles were analyzed by 16S rDNA sequencing and UHPLC/Q-TOF-MS. C3G attenuated colitis severity, improved histological damage, increased interleukin-10, and reduced IL-1β, IL-6, and TNF-α levels. NF-κB activation was inhibited, accompanied by enhanced anti-inflammatory macrophage polarization. C3G also altered gut microbiota composition, reducing pathogenic taxa and enriching beneficial microbes. Metabolomic analysis identified 1-deoxynojirimycin (1-DNJ) as associated with C3G treatment. Overall, C3G modulates inflammatory responses, microbiota composition, and NF-κB signaling in experimental colitis and is associated with changes in 1-DNJ, warranting further mechanistic investigation.