Alleviation Effect of the Secondary Metabolite of Anthocyanin (Protocatechuic Acid) on Heterocyclic Amine (IQ)-Induced Liver Injury and Its Underlying Mechanism

Increased consumption of thermally processed meats caused a high risk of accumulation of heterocyclic amines (HCAs), which would lead to livery injuries and carcinogenic diseases in daily life. Our previous study found that cyanidin-3-glucoside expressed a protective effect on 2-amino-3-methylimidazo [4,5- f ] quinoline (IQ)-induced liver injury, but its intrinsic mechanism in vivo was unclear. Thus, this study was aimed at investigating the alleviation effect of the secondary metabolite of anthocyanin (protocatechuic acid) on IQ-induced liver dysfunction and its underlying mechanism. The results demonstrated that 4 weeks of IQ (30 mg/kg) administration to C57BL/6 mice induced significant oxidative stress and liver injury, which were suppressed by PCA (10 and 20 mg/kg) supplement. Meanwhile, IQ-mediated liver inflammation was mitigated by PCA supplementation via suppressing NF-κB/MAPK pathways of signaling. Moreover, the PCA supplement significantly reversed IQ-induced intestinal damage and tight junction dysfunction. Concurrently, 16s rRNA sequencing data indicated by PCA reversed the IQ-disturbed SCFAs content and gut microbiota. Analysis of the correlation between intestinal damage and gut microbiota, with manufacturers of hepatic dysfunction, underscored the significance of the gut–liver axis in PCA-relieved liver injury stimulated via IQ. Taken together, PCA reduced IQ-induced liver damage via modifying the NF-κB/MAPK-NLRP3 inflammatory cascade, which was controlled by intestinal barrier failure mediated by the gut microbiota. In summary, our results offer new perspectives on microbiome-targeted therapeutic strategies for liver dysfunction associated with IQ.