Bioflavonoid combination attenuates diabetes-induced nephropathy in rats via modulation of MMP-9/TIMP-1, TGF-ß, and GLUT-4-associated pathways.

ABSTRACT

Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-ß. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-ß, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.