title: Naringenin inhibits α-glucosidase activity: a promising strategy for the regulation of postprandial hyperglycemia in high fat diet fed streptozotocin induced diabetic rats.
abstract: 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 (T2D). Postprandial glucose levels can be regulated through α-glucosidase inhibition. The present study aims to demonstrate the potent inhibitory role of naringenin against α-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 α-glucosidase thereby competing with α-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 α-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 α-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 α-glucosidase inhibitor acarbose. Our findings clearly indicate that naringenin dampens postprandial glycemic response and offers a potential complementary approach in the management of T2D.
authors.affiliation: Structural Biology Lab, Centre for Bio Medical Research, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
authors.forename: David Hansi
authors.initials: DH
authors.lastname: Priscilla
authors.affiliation: Structural Biology Lab, Centre for Bio Medical Research, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Roy
authors.affiliation: Structural Biology Lab, Centre for Bio Medical Research, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Suresh
authors.affiliation: Structural Biology Lab, Centre for Bio Medical Research, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Structural Biology Lab, Centre for Bio Medical Research, School of Bio Sciences and Technology, VIT University, Vellore 632 014, Tamil Nadu, India. Electronic address: m.kavitha@vit.ac.in.
authors.forename: Kavitha
authors.initials: K
authors.lastname: Thirumurugan
mesh_terms: D000818:Animals; D001665:Binding Sites; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D059305:Diet, High-Fat; D004789:Enzyme Activation / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007422:Intestines / Q000201:enzymology; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
chemical_list: D001786:Blood Glucose; D044950:Flavanones; D065089:Glycoside Hydrolase Inhibitors; D008024:Ligands; D013311:Streptozocin; C005273:naringenin
keywords: Molecular docking; Naringenin; Postprandial hyperglycemia; Type 2 diabetes; α-Glucosidase