Inhibitory Effects and Underlying Molecular Mechanisms of Wheat Alkylresorcinols on α-Glucosidase and α-Amylase Activities

WEN Rou; GUO Mengmeng; LU Hang; LI Shuguo

doi:10.13982/j.mfst.1673-9078.2025.5.0279

Abstract：The inhibitory effects of wheat alkylresorcinols(ARs)on α-amylase and α-glucosidase(key enzymes in carbohydrate digestion)and the underlying mechanisms were examined.The hypoglycemic effect of wheat ARs was determined in in vitro α-glucosidase and α-amylase inhibition tests.The inhibition types of ARs towards α-amylase andα-glucosidase were inferred by enzymatic kinetics and Lineweaver-Burk curves.The underlying mechanisms were further evaluated through molecular docking and molecular simulation dynamics.When the mass concentration of ARs was 100 μg/mL,the inhibition rates of α-amylase and α-glucosidase activities were 58.68％and 57.49％,respectively,which were slightly lower than those of α-amylase and α-glucosidase activities(63.51％and 60.20％)at an acarbose(positive control)mass concentration of 100 μg/mL.The half-maximal inhibitory concentration of ARs against α-amylase and α-glucosidase were 48.02 and 33.29 μg/mL,respectively.The inhibition types were identified as reversible and competitive inhibitions for both enzymes.The docking score was-4.864,and the molecular mechanics with generalized Born and surface area solvation result was-44 kcal/mol.The low docking score and binding free energy indicated that ARs bound more stably to and had a greater inhibitory effect on α-glucosidase than on α-amylase.At the molecular level,ARs bound to the amino acids PHE327,ASN544,LYS811,and SER556 of α-glucosidase mainly through hydrogen bonds,hydrophobic interactions,and water bridges.Experimental studies and theoretical analysis showed that wheat ARs strongly inhibit α-amylase and α-glucosidase and thus can be used as a natural inhibitor of these enzymes.These findings may guide the development of functional foods or low-glycemic-index foods for regulating blood glucose.