Gomisin A and metformin co-treatment attenuates diabetic nephropathy and cardiovascular dysfunction by modulating the AGE/RAGE pathway in a diabetic rat model.

Diabetic nephropathy (DN) is a severe complication of type 2 diabetes mellitus (T2DM) that is frequently accompanied by cardiovascular disease (CVD) and chronic kidney disease (CKD). The current therapeutic options for DN and CVD are limited and often produce significant adverse effects. In this study, we evaluated the renal and cardioprotective effects of natural Gomisin A, alone and in combination with metformin, in a diabetic model. While treatment with Gomisin A at 20 mg/kg slightly improved glycemic control and renal function, co-administration with metformin yielded better results. The combined treatment significantly lowered blood glucose levels and improved β-cell integrity. It also prevented renal hypertrophy and reduced inflammation, as evidenced by decreased serum creatinine, urea, phosphorus, lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels. Additionally, the combination modulated the AGE/RAGE pathway, thereby downregulating NF-κB expression, reducing proinflammatory cytokines, and lowering TGF-β expression in renal tissues. Cardiac protective effects were also observed, including inhibition of myocardial thickening and hypertrophy. These findings suggest that Gomisin A and metformin work synergistically to mitigate the progression of DN and CVD, supporting the potential of Gomisin A as a nutraceutical adjunct to conventional anti-diabetic treatments.