Synergistic Effects of Combined Anthocyanin and Metformin Treatment for Hyperglycemia In Vitro and In Vivo

The mechanism underlying the hypoglycemic effect of the simultaneous use of metformin and anthocyanin-rich foods is not yet clear. Hence, the effects and possible mechanisms of action of these substances, alone and in combination, were evaluated in insulin-resistant HepG2 cells and a diabetic mouse model. The results indicated that anthocyanin and metformin had a significant synergistic effect on glucose consumption (CI < 0.9) compared with metformin alone in HepG2 cells. In the mouse model, combined treatment (50 and 100 mg/kg metformin + anthocyanin groups) demonstrated synergistic restorative effects on the blood glucose level, insulin resistance, and organ damage in the liver, pancreas, and ileum. Additionally, combined metformin and anthocyanin treatment suppressed protein tyrosine phosphatase 1B expression and regulated the PI3K/AKT/GSK3β pathway. Combined treatment also altered the gut microbial composition and structure by increasing the relative abundance of beneficial bacteria and the short-chain fatty acid content. These results suggest that the use of anthocyanins can enhance the efficacy of metformin treatment for hyperglycemia and provide a reference for further clinical research regarding nutrition and supplementary treatment.