Therapeutic potential of quercetin and metformin combination in restoring vascular function in type 1 diabetic rats

Background : The synergistic effects of quercetin + metformin on type 1 diabetes and endothelial dysfunction is not reported so far. Methods : Eight-week-old male Sprague Dawley rats were treated with Streptozotocin (STZ) to induce diabetes and divided into four groups viz. diabetic control (1 % w/v carboxymethyl cellulose (CMC)), quercetin (10 mg/kg in 1 % CMC), metformin (180 mg/kg in 1 % CMC) and quercetin + metformin (10 + 180 mg/kg in 1 % CMC) group as per their treatment regime. The rats without STZ treatment served as non-diabetic control (1 % CMC). All the rats were treated for 30 days as per the treatment regimes and analyzed for oral glucose tolerance, plasma lipid profile, liver enzymes, vascular function, histology, and immunohistochemistry. Results : The combination of quercetin + metformin treatment more effectively restored endothelial function and improved hyperglycemia, levels of blood lipids, and liver enzymes in T1D rats as compared with quercetin or metformin alone. Besides this, it increased levels of eNOS and SIRT-1 and decreased levels of 3-nitrotyrosine, VCAM-1, and CD-31, which are known to improve NO production, vascular cell senescence, and endothelial barrier function. Conclusions : Quercetin enhances metformin activity to lower hyperglycemia and restore endothelial function in type 1 diabetic rats.