Pentacyclic triterpenes as α-glucosidase and α-amylase inhibitors: Structure-activity relationships and the synergism with acarbose

In this paper, the inhibition of alpha-amylase and alpha-glucosidase by nine pentacyclic triterpenes was determined. For alpha-amylase inhibitory activity, the IC50 values of ursolic acid, corosolic acid, and oleanolic acid were 22.6 +/- 2.4 mu M, 31.2 +/- 3.4 mu M, and 94.1 +/- 6.7 mu M, respectively. For alpha-glucosidase inhibition, the IC50 values of ursolic acid, corosolic acid, betulinic acid, and oleanolic acid were 12.1 +/- 1.0 mu M, 17.2 +/- 0.9 mu M, 14.9 +/- 1.9 mu M, and 35.6 +/- 2.6 mu M, respectively. The combination of corosolic acid and oleanolic acid with acarbose showed synergistic inhibition against alpha-amylase. The combination of the tested triterpenes with acarbose mainly exhibited additive inhibition against alpha-glucosidase. Kinetic studies revealed that corosolic acid and oleanolic acid showed non-competitive inhibition and acarbose showed mixed-type inhibition against alpha-amylase. The results provide valuable implications for the triterpenes (ursolic acid, corosolic acid, and oleanolic acid) alone or in combination with acarbose as a therapeutic agent for the treatment of diabetes mellitus. (C) 2017 Elsevier Ltd. All rights reserved.