Protective role of cyanidin‐3‐ <i>O</i> ‐glucoside in 2‐amino‐3‐methylimidazo[4,5‐ <i>f</i> ]quinoline‐induced gastrointestinal injury: focus on oxidative stress, inflammation, intestinal barrier and gut microbiota

BACKGROUND: 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), a typical heterocyclic amine, is a common dietary carcinogen raising gastric and colorectal cancer risks. As an abundant anthocyanin monomer with established antioxidant and anti-inflammatory activities, cyanidin-3-O-glucoside (C3G) might attenuate IQ toxicity. Nevertheless, whether and how C3G alleviates IQ-triggered gastrointestinal damage remains unclarified. This study investigated the protective mechanisms of C3G against IQ-induced gastrointestinal injury in mice using biochemical assays, histopathology, western blotting, 16S rRNA sequencing, and molecular simulation. RESULTS: The results demonstrated that C3G significantly ameliorated IQ-induced gastric and colonic tissue damage. It effectively reduced key inflammatory markers (nitric oxide, interleukin-6, and tumor necrosis factor-α) and the oxidative stress marker MDA in repaired mouse tissues and serum, while elevating antioxidant enzyme levels. Western blot analysis revealed tissue-specific protective mechanisms. In gastric tissue, C3G activated the Keap1-Nrf2 pathway to enhance antioxidant capacity and suppressed the NF-κB pathway to attenuate inflammation. In the colon, C3G inhibited inflammation via MyD88/TLR4/NF-κB signaling and upregulated the expression of tight junction proteins to restore intestinal barrier function. Gut microbiota analysis revealed that C3G reversed IQ-induced dysbiosis and increased the relative abundance of beneficial bacteria such as Roseburia and Enterorhabdus. Molecular dynamics simulations demonstrated that C3G could enhance IKKβ stability and interfere with its phosphorylation by forming hydrogen bonds with residues ASP151 and ASP109. CONCLUSION: This study elucidates that C3G alleviates IQ-induced gastrointestinal injury through a multidimensional mechanism involving microbiota modulation, antioxidation, anti-inflammation, and intestinal barrier repair, providing a theoretical basis for anthocyanin-based dietary interventions against heterocyclic amine toxicity. © 2026 Society of Chemical Industry.