Polyphenols from Broussonetia papyrifera displaying potent alpha-glucosidase inhibition.
The organic extract of the roots of Broussonetia papyrifera showed extremely high alpha-glucosidase inhibitory activity with an IC50 of around 10 microg/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 alpha-glucosidase inhibitory activity to identify their inhibitory potencies and kinetic behavior. The most potent inhibitor, 10 (IC50=2.1 microM, Ki=2.3 microM), has an inhibitory activity slightly higher than that of the potent alpha-glucosidase inhibitor deoxynojirimycin (IC50=3.5 microM). The novel alpha-glucosidase inhibitors 11 (IC50=27.6 microM) and 12 (IC50=33.3 microM) are similar in activity to sugar-derived alpha-glucosidase inhibitors such as voglibose (IC50=23.4 microM). 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 microM, respectively. In kinetic studies, chalcones (1-4) exhibited noncompetitive inhibition characteristics, whereas the others (5-12) showed mixed behavior.
Ryu
Hyung Won
HW
Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture and Life Science, Graduate School of Gyeongsang National University, Jinju 660-701, South Korea.
Lee
Byong Won
BW
Curtis-Long
Marcus J
MJ
Jung
Sunin
S
Ryu
Young Bae
YB
Lee
Woo Song
WS
Park
Ki Hun
KH
D031623:Broussonetia / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005419:Flavonoids / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D010636:Phenols / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D059808:Polyphenols; D000520:alpha-Glucosidases / Q000032:analysis
D004791:Enzyme Inhibitors; D005419:Flavonoids; D065089:Glycoside Hydrolase Inhibitors; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D000520:alpha-Glucosidases