α-Glucosidase Inhibitors from Marrubium astracanicum: Isolation and Molecular Docking

Marrubium astracanicum Jacq., Lamiaceae, is an herbaceous plant distributed in Iran, Turkey, and southern Caucasia. In the present study, alpha-glucosidase inhibitory principles of M. astracanicum aerial parts were investigated by a bioassay-guided approach. The extraction procedure from the plant aerial parts was carried out successively using petroleum ether, ethyl acetate, and methanol. The ethyl acetate extract, with the highest in vitro alpha-glucosidase inhibitory activity, was subjected to further chemical investigation. The structures of the isolated compounds were elucidated by H-1-NMR and C-13-NMR spectral analyses as apigenin-7-O-(3 ''-(E)-p-coumaroyl)-beta-D-glucoside, apigenin-7-O-(6 ''-(E)-p-coumaroyl)-beta-D-glucoside, martynoside, apigenin-7-O-beta-D-glucoside, and verbascoside. In addition, the antidiabetic potential of the isolated compounds was evaluated in an in vitro alpha-glucosidase inhibitory assay, and kinetic and molecular docking studies were done for the most active compound. Apigenin-7-O-(3 ''-(E)-p-coumaroyl)-beta-D-glucoside and apigenin-7-O-(6 ''-(E)-p-coumaroyl)-beta-D-glucoside showed the most potent in vitro alpha-glucosidase inhibitory activity with IC50 values of 57.4 +/- 1.2 and 186.4 +/- 2.5 mu M, respectively, which was about 4 to 13 times lower than the IC50 value of the reference compound acarbose (751.2 +/- 0.4 mu M).