Apple Polyphenol Mitigates Diabetic Nephropathy via Attenuating Renal Dysfunction with Antioxidation in Streptozotocin-Induced Diabetic Rats

Diabetic nephropathy (DN) is a major cause of morbidity and mortality among patients with diabetes mellitus (DM). Studies have highlighted the critical role of reactive oxygen species (ROS) in the pathogenesis of DM and its complications. Apple polyphenol (AP) has demonstrated antioxidant properties in various models. In this study, we investigated the effects of AP on DN in a rat model. Type 1 diabetes was induced in Sprague-Dawley rats via a single intraperitoneal injection of streptozotocin (65 mg/kg) (n = 8). Rats with blood glucose levels exceeding 250 mg/dL were treated with AP at dosages of 0.5%, 1%, or 2% (w/w) in drinking water for 10 weeks. AP administration significantly improved early-stage DN markers, including reductions in the blood urea nitrogen-to-creatinine ratio and the urinary albumin-to-creatinine ratio (ACR), in a dose-dependent manner. AP treatment also significantly lowered blood triglyceride levels and reduced lipid peroxidation in kidney tissues. Histological analysis revealed that AP attenuated renal hydropic change, reduced glomerular basement membrane thickening, and restored mitochondrial morphology in diabetic rats. Additionally, the upregulation of transforming growth factor-beta (TGF-beta) observed in the diabetic kidney was attenuated by AP treatment. In H2O2-stimulated rat mesangial cells, AP reduced ROS levels, accompanied by a reduction in TGF-beta expression. These findings suggest that AP exerts protective effects against DN by improving renal function and mitigating oxidative stress, indicating its potential as a nutraceutical supplement for slowing DN progression.