Inhibitory effect of hesperetin on α-glucosidase: Molecular dynamics. simulation integrating inhibition kinetics

The alpha-glucosidase inhibitor is of interest to researchers due to its association with type-2 diabetes treatment. Hesperetin is a flavonoid with natural antioxidant properties. This paper presents an evaluation on the effects of hesperetin on alpha-glucosidase via inhibitory kinetics using a Molecular Dynamics (MD) simulation integration method. Due to the antioxidant properties of hesperetin, it reversibly inhibits alpha-glucosidase in a slope-parabolic mixed-type manner (IC50 = 0.38 +/- 0.05 mM; K-slope = 0.23 +/- 0.01 mM), accompanied by tertiary structural changes. Based on computational MD and docking simulations, two hesperetin rings interact with several residues near the active site on the alpha-glucosidase, such as Lys155, Asn241, G1u304, Pro309, Phe311 and Arg312. This study provides insight into the inhibition of alpha-glucosidase by binding hesperetin onto active site residues and accompanying structural changes. Hesperetin presents as a potential agent for treating alpha-glucosidase-associated type-2 diabetes based on its a-glucosidase-inhibiting effect and its potential as a natural antioxidant. (C) 2017 Elsevier B.V. All rights reserved.