Gallic acid improves the metformin effects on diabetic kidney disease in mice

Objectives Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. Methods Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). Results Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). Conclusion Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Automated summary

This study aimed to test whether a combination of gallic acid and metformin can exert a synergistic effect on diabetic kidney disease in diabetic mice model. Our results demonstrated that compared to the untreated diabetic mice, all three strategies (gallic acid, metformin, and the combination of gallic acid and metformin) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMPK/SIRT1 signaling in kidney tissues. Notably, the combination strategy provided the most potent renal protection effects.