Renoprotective impact of Dapagliflozin and Mulberry extracts toward Fr-STZ induced diabetic nephropathy in rats: Biochemical and Molecular aspects

Among the most typical reasons of end-stage renal disease (ESRD) is diabetic nephropathy (DN), which is also rated as a major microvascular complication of diabetes mellitus. The existent study looked at the impact of dapagliflozin, mulberry fruit and leaves extracts and their combination on the kidney of diabetic rats. To induce diabetic nephropathy, experimental rats were supplied with 10% fructose (Fr) in drinking water for the first two weeks. Each Fr-fed animal received an intraperitoneal injection of a low single dose of STZ (40 mg/kg) after being fasted for the whole night. Sixty albino rats were separated into six equivalent groups. Group I control rats, group II untreated diabetic rats, group III–VI are diabetic groups; received dapagliflozin for 4 weeks, mulberry fruit extract, mulberry leaves extract and combination of DAPA, MFE and MLE, respectively for 6 weeks. Untreated diabetic rats exhibited considerable rise in serum glucose, urea, creatinine, KIM-1, β2-MG, TNF-α, and TGβ1 levels compared to control rats, while treated diabetic ones manifested significant decrease in these measures in contrast to the untreated diabetic rats. Also, renal tissue IL-6, NF-κB and NADPH oxidase manifested significant increase in untreated diabetic rats, while treated groups revealed significant decline in comparison to the untreated one. DAPA and mulberry fruit and leaves extracts optimized IL-10 and renin expression in renal tissue. Histopathological picture of kidney, revealed significant improvement in rats received DAPA and mulberry extracts compared to untreated diabetic rats. It could be concluded that, DAPA, mulberry fruits and leaves extracts alleviated diabetic nephropathy complications. Therefore, combining these ingredients in a supplement may be promising for modulating diabetic nephropathy.