Postprandial Hyperglycemia Lowering Effect of the Isolated Compounds from Olive Mill Wastes - An Inhibitory Activity and Kinetics Studies on α-Glucosidase and α-Amylase Enzymes

In the present study, we isolated seven compounds from olive mill wastes (OMW), one of them being novel, and investigated their antidiabetic potential through inhibition of α-glucosidase and α-amylase enzymes. To assist the possible characterization of the mechanisms involved, we analyzed the inhibitory kinetics of the active compounds. Oleanolic acid , maslinic acid , 1-acetoxypinoresinol , and luteolin-7-β-d-glucoside exhibited stronger inhibitory activity against both enzymes, with IC values less than or close to that of acarbose. Other compounds pinoresinol and hydroxytyrosol-containing compounds (hydroxytyrosol acetate , hydroxytyrosol , and the novel one, 3,4-dihydroxyphenyl-2-methoxyethanol ) showed weak activity against both enzymes (IC > 500 μM). Our findings show that, first, the esterification of C-1 of the furofuran ring is the key feature for the stronger activity of 1-acetoxypinoresinol against both enzymes IC = 13.9 and 313 μM for α-amylase and α-glucosidase, respectively), as compared to pinoresinol; second, the oleanane skeletons of the triterpenes ( and ) are optimum for the α-glucosidase and α-amylase inhibitory activities, while the hydroxytyrosol moiety may be responsible for the weak activities of , , and . Additionally, kinetics analysis of , , and revealed that they inhibit α-glucosidase in mixed-type, noncompetitive, and uncompetitive mechanisms, respectively. We confirmed their mechanisms by measuring their affinity for the enzyme ( ), and they all (, , and ) had a higher affinity for the enzyme, > 1. This work adds more value to OMW for further studies as a potential source of lead antidiabetic compounds for the prevention and/or treatment of type 2 diabetes.