Functional food prevents diabetic nephropathy in a rat model through inhibition of aldose reductase and accumulation of advanced glycation end-products

Abstract

Diabetic nephropathy (DN) is a chronic microvascular complication of diabetes mellitus, characterized by glomerulomegaly, podocytopathy, and proteinuria. Among the many molecular mechanisms, accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation and sorbitol accumulation due to increased aldose reductase (AR) activity are implicated in DN. We previously identified some functional foods and their bioactive molecules for inhibitory potential against AGE formation and, AR activity. Based on those studies, in this study, we formulated a functional food (FF) mix- composed of amla, turmeric, cinnamon, ginger, and black pepper in a specific proportion and tested its efficacy against DN in a rat model. Two-month-old Sprague Dawley rats were grouped into control (C), streptozotocin-induced diabetes (D), and diabetes treated with FF at two doses (FF1–0.85 g and FF2–4.25 g/ 100 g diet). The animals were maintained for 20 weeks on respective diets after the induction of diabetes. Elevated serum albumin, creatinine, and urea were observed in the untreated diabetic group compared to the control. These changes were significantly ameliorated by FF supplementation. FF2 showed better efficacy than FF1 in preventing proteinuria, as reflected in the albumin and creatinine ratio. Further, FF prevented diabetes induced AGE accumulation, inflammation, and activation of the polyol pathway in the kidney. The FF decreased the expression of TGF-β in the diabetic kidney and prevented fibrotic changes. Most importantly, FF prevented the depletion of podocyte slit diaphragm proteins and histological changes. These results provide a mechanistic basis of FF and its potential against progression of DN in a rat model.