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 and α-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 lowglycemic-index foods for regulating blood glucose.
