Department of Nephrology, Jiangnan University Medical Center (JUMC), Wuxi, China.
Department of Nephrology, Wuxi No. 2 People's Hospital, Affiliated Wuxi Clinical College of Nantong University, Wuxi, China.
Ren Fail. 2023 Dec;45(1):2183726. doi: 10.1080/0886022X.2023.2183726. Epub 2023 Mar 2.
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.
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).
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).
Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.
二甲双胍是一种抗糖尿病药物,用于治疗 2 型糖尿病。没食子酸是一种酚酸,已被证明是治疗糖尿病肾病的潜在药物候选物,糖尿病肾病是糖尿病的一种重要并发症。我们旨在测试没食子酸和二甲双胍的联合用药是否对糖尿病小鼠模型中的糖尿病肾病有协同作用。
腹腔注射链脲佐菌素(65mg/kg)诱导糖尿病肾病小鼠模型。用生理盐水(Vehicle)、没食子酸(GA)(30mg/kg)、二甲双胍(MET)(200mg/kg)或没食子酸(30mg/kg)和二甲双胍(200mg/kg)联合(GA+MET)处理糖尿病小鼠。
与未治疗的糖尿病小鼠相比,三种策略(GA、MET 和 GA+MET)均能改善肾脏形态和功能,减轻肾脏组织中的氧化应激,恢复 AMP 激活的蛋白激酶(AMPK)/沉默交配型信息调节 2 同源物 1(SIRT1)信号通路,从而改善糖尿病小鼠的肾脏功能。值得注意的是,联合策略(GA+MET)比任何单一策略(GA 或 MET)提供更强的肾脏保护作用。
我们的研究结果支持了这样一种假说,即没食子酸可能作为二甲双胍的潜在补充物,增强二甲双胍的治疗效果。