Biochemical and molecular evaluation of resveratrol and selenium nanoparticles in managing type 2 diabetes and its complications.

The therapeutic potential of dietary polyphenols, such as resveratrol (Res) and elemental selenium nanoparticles (SeNPs), has gained increasing attention for the treatment and management of type 2 diabetes mellitus (T2DM). In this study, we investigated a novel therapeutic strategy using chitosan-stabilized Res/SeNPs (CS/Res/SeNPs) in a mouse model of T2DM induced by high-fat diet (HFD) feeding combined with multiple low-dose streptozotocin (STZ) injections. We evaluated the effects of these nanoparticles on glucose and insulin levels, oxidative/antioxidant balance, expression of apoptotic and anti-apoptotic genes, and inflammatory mediators using biochemical, histopathological, and molecular docking analyses. Treatment with free Res, CS/Res/SeNPs-5, CS/Res/SeNPs-10, and Metformin (Met) improved hyperglycemia, insulin resistance (IR), and dyslipidemia, and normalized elevated liver and kidney biomarkers. These treatments also exhibited anti-inflammatory, antioxidant, and anti-apoptotic effects. CS/Res/SeNPs-10 showed the most potent hepatoprotective and anti-diabetic effects. The docking results revealed that Res binds to key insulin signaling proteins, such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR). Collectively, our findings highlight the therapeutic promise of CS/Res/SeNPs in managing T2DM complications and suggest a cost-effective strategy to enhance health outcomes and quality of life in diabetic patients.