Duranta repens L. reverses hepatic and peripheral insulin resistance in fructose-induced hyperinsulinaemic rats – Experimental and computational findings

Abstract

The present study investigated the effect of hydroalcoholic extract of Duranta repens Linn over gluconeogenesis, glycolysis, glycogenesis, leptin, and dipeptidyl peptidase-4 regulation in fructose-induced insulin-resistant rats. Initially, hyperinsulinemia was induced by supplementing fructose in drinking water for fifty-four days. Glucose intolerance was confirmed using oral glucose tolerance test and subjected for extract treatment for next thirty days. After thirty days of treatment, animals fasted and an oral glucose tolerance test was performed followed by an insulin tolerance test. After that, animals were overdosed with anesthetic ether, blood was collected to separate plasma and serum. Further, multiple biochemical parameters i.e. lipid profile, hepatic enzymes, enzymatic and non-enzymatic antioxidant biomarkers, glycogen content, leptin, and the glucagon-like peptide-1 level were quantified. Additionally, the glucose uptake in rat hemidiaphragm and hepatic histology were performed. Further, molecular docking was performed using AutoDock Vina and the ligand pose with minimum binding energy was chosen to visualize the ligand-protein interaction. After the thirty days of treatment with extract, it was observed to ameliorate the fructose-induced alterations in body weight, food intake, and water intake. Further, it improved glucose tolerance. This was confirmed via the quantification of the total triglycerides and assessing oral glucose and insulin tolerance test. Additionally, it also improved the level of hepatic enzymes involved in gluconeogenesis and glycolysis. Also, it upregulated the leptin pathway; however, did not influence the dipeptidyl peptidase-4-glucagon-like peptide-1. Similarly, a docking study predicted scutellarein, pseudo-ginsenoside-RT1, repennoside, and durantanin I as probable lead hits from Duranta repens as prime regulators of gluconeogenesis. Additionally, molecular docking revealed scutellarein, pseudo-ginsenoside-RT1, repennoside, and durantanin I as the probable lead hits in regulating the enzymes involved in hepatic glucose catabolism and anabolism. Treatment with the hydroalcoholic extract of Duranta repens extract ameliorated fructose-induced gluconeogenesis, glycolysis, glycogenesis, and leptin regulation; however, did not influence the dipeptidyl-peptidase 4- glucagon-like peptide-1 pathway.