Postprandial Hyperglycemia Lowering Effect of the Isolated Compounds from Olive Mill Wastes An Inhibitory Activity and Kinetics Studies on a Glucosidase and a 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 a glucosidase and a amylase enzymes. To assist the possible characterization of the mechanisms involved, we analyzed the inhibitory kinetics of the active compounds. Oleanolic acid 1, maslinic acid 2, 1 acetoxypinoresinol 3, and luteolin 7 O b d glucoside 6 exhibited stronger inhibitory activity against both enzymes, with IC50 values less than or close to that of acarbose. Other compounds pinoresinol and hydroxytyrosol containing compounds (hydroxytyrosol acetate 4, hydroxytyrosol 7, and the novel one, 3,4 dihydroxyphenyl 2 methoxyethanol 5) showed weak activity against both enzymes (IC50 500 mM) 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 3 against both enzymes (IC50 13.9 and 313 mM for a amylase and a glucosidase, respectively) as compared to pinoresinol; second, the oleanane skeletons of the triterpenes (1 and 2) are optimum for the a glucosidase and a amylase inhibitory activities, while the hydroxytyrosol moiety may be responsible for the weak activities of 4, 5, and 7. Additionally, kinetics analysis of 1, 6, and 3 revealed that they inhibit a glucosidase in mixed type, noncompetitive, and uncompetitive mechanisms, respectively. We confirmed their mechanisms by measuring their affinity for the enzyme (Ki) and they all (1, 6, and 3) had a higher affinity for the enzyme, Ki 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.
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