Comprehending the mechanism of catechins against α-glucosidase by multispectral data and their antidiabetic effects in vivo

Diabetes mellitus (DM) is a common metabolic disorder characterized by the elevated blood glucose levels. Catechins comprising four isomers, (+)-catechin [(+)CT], (-)-catechin [(-)CT], (+)-epicatechin [(+)ECT] and (-)-epicatechin [(-)ECT], are a family of Flavanols widespread in natural sources. In this study, four catechins were extensively evaluated against diabetes-related Enzymes, of which (+)CT (IC₅₀ = 63.5 μM) and (+)ECT (IC₅₀ = 73.8 μM) were revealed with significant activity against α-glucosidase, about 6.1 and 5.2 times higher than the positive control, acarbose (IC₅₀ = 388.0 μM). Enzyme kinetic study manifested that (+)CT and (+)ECT were reversible inhibitors of α-glucosidase via noncompetitive and non-competitive/uncompetitive-mixed modes, respectively. Fluorescence quenching, UV-Visible spectroscopy, circular dichroism (CD), surface hydrophobicity and molecular docking simulations jointly manifested that (+)CT induced alteration in the secondary structure and hydrophobic microenvironment of α-glucosidase primarily through hydrogen bonding and hydrophobic interactions; while (+)ECT exerted effects mainly through electrostatic interactions. The in vivo oral starch and sucrose tolerance tests demonstrated that both (+)CT and (+)ECT significantly reduced the postprandial blood glucose (PBG) levels in mice. In conclusion, catechins especially (+)CT and (+)ECT have the potency to improve postprandial hyperglycemia by inhibiting α-glucosidase.

Catechins; Enzyme kinetics; Inhibitory mechanism; Postprandial blood glucose; α-Glucosidase.