Polyphenols from Broussonetia papyrifera displaying potent alpha-glucosidase inhibition = 닥나무로부터 분리한 폴리페놀성 화합물의 강한 alpha-glucosidase 저해활성

Abstract

The organic extract of the roots of Broussonetia papyrifera showed extremely high a-glucosidase inhibitory activity with an IC50 of around 10 μg/mL. Due to its potency, subsequent bioactivity-guided fractionation of the chloroform extract led to 12 polyphenols, 1-12, 4 of which were identified as chalcones (1-4), another 4 as flavans (5-8), 2 as flavonols (9 and 10), and 2 others as the novel species benzofluorenones (11 and 12). Broussofluorenone A (11) and broussofluorenone B (12) emerged as new compounds possessing the very rare 5, 11-dioxabenzo[b]fluoren-10-one skeleton. These compounds (1-12) were evaluated for a-glucosidase inhibitory activity to identify their inhibitory potencies and kinetic behavior. The most potent inhibitor, 10 (IC50 = 2.1 μKI = 2.3 μM) has an inhibitory activity slightly higher than that of the potent α-glucosidase inhibitor deoxynojlrimycln (IC50 = 3.5 μM). The novel a-glucosidase inhibitors 11 (IC50 = 27.6 μM) and 12 (IC 50 = 33.3 μM) are similar in activity to sugar-derived a-glucosidase inhibitors such as voglibose (IC50 = 23.4 μM). Interestingly, major constituents (1, 2, 6, 7, 9, and 10) of B. papyrifera displayed significant inhibitory activity with IC50 values of 5.3, 11.1, 12.0, 26.3, 3.6, and 2.1 μM, respectively. In kinetic studies, chalcones (1-4) exhibited noncompetitive inhibition characteristics, whereas the others (5-12) showed mixed behavior.