Naringenin inhibits α-glucosidase activity: A promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats

Obesity and the onset of diabetes are two closely linked medical complications prevalent globally. Postprandial hyperglycemia is one of the earliest abnormalities of glucose homeostasis associated with type 2 diabetes (VD). Postprandial glucose levels can be regulated through alpha-glucosidase inhibition. The present study aims to demonstrate the potent inhibitory role of naringenin against alpha-glucosidase activity. The mode of inhibition of naringenin was examined by measuring enzyme activity in vitro with different concentrations of substrate using Lineweaver-Burk plot analysis. It shows competitive inhibition towards mammalian alpha-glucosidase thereby competing with alpha-limit dextrins and oligosaccharide residues for binding in the active site. Similar results have been obtained from the molecular docking analyses, where naringenin shows preferential binding for the active sites in each of the evaluated human intestinal a-glucosidase enzymes. Post-docking intramolecular hydrogen bonding analysis shows water molecule mediated hydrogen bonding for N-terminal maltase glucoamylase and N-terminal sucrase isomaltase. Naringenin's docked pose in the C-terminal maltase glucoamylase active site does not show any particular water mediated interaction similar to the co-crystallized acarbose. Further, our results suggest that naringenin (25 mg/kg) exerts significant inhibition of intestinal alpha-glucosidase activity in vivo thereby delaying the absorption of carbohydrates in T2D rats, thus resulting in significant lowering of postprandial blood glucose levels. Both in vitro and in vivo results were compared to the commercially available alpha-glucosidase inhibitor acarbose. Our findings clearly indicate that naringenin dampens postprandial glycemic response and offers a potential complementary approach in the management of T2D. (C) 2014 Elsevier Ireland Ltd. All rights reserved.