Cyclopeptide alkaloids of Ziziphus oxyphylla Edgw as novel inhibitors of α-glucosidase enzyme and protein glycation

Three cyclopeptide alkaloids, nummularine-R (1), nummularin-C (2), and hemsine-A (3), isolated from locally used antidiabetic plant Ziziphus oxyphylla Edgw (Rhamnaceae), showed a potent α-glucosidase inhibition, and moderate anti-glycation activities but no inhibition for α-chymotrypsin. This is the first report of the antidiabetic activities of cyclopeptide alkaloids. All compounds 1-3 exhibited inhibition for α-glucosidase enzyme having IC 50 = 212.1 ± 1.6 μM, 215.1 ± 1.2 μM, and 394.0 ± 2.4 μM respectively, which are more potent than the standard, 1-deoxynojirimycin (IC50 = 441.0 ± 0.1 μM). Compounds 1 (IC50 = 720.2 ± 10.9 μM), and 3 (IC50 = 277.7 ± 7.6 μM) were also found to have a moderate anti-glycation activity. All compounds were non-toxic to PC-3 cell line. These compounds seem to have potential to control the postprandial hyperglycemia, and associated diabetes complications due to glycation of proteins. © 2011 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.