Polyphenols from Broussonetia papyrifera Displaying Potent α-Glucosidase Inhibition

Abstract

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.

The α-Glucosidase and α-Amylase Enzyme Inhibitory of Hydroxytyrosol and Oleuropein

“…Several reports have investigated the inhibitory effect of luteolin and luteolin-7-O-glucoside against α-glucosidase and α-amylase. In fact, luteolin inhibited α-glucosidase by 36 and was stronger than acarbose, whereas its inhibitory effect against α-amylase was less potent than acarbose 19 . On the other hand, gallic acid, vanillic acid, quercetin and p-coumaric acid isolated from finger millet were shown to be potent inhibitors against α-amylase with respective inhibition of 67.7 , 71.9 , 73.5 and 62.5 and showed uncompetitive inhibition 20 .…”

Starch Hydrolase Inhibitors from Edible Plants

“…Four isoprenylated flavanes, kazinol A (11) and its derivative kazinol B (12) were isolated from the roots of paper mulberry Broussonetia papyrifera via bioassayguided fractionation (Ryu et al, 2010). They show strong inhibition activity on yeast a-glucosidase with IC 50 values of 12 and 26.3 mM.…”

“…Two chalcones, broussochalcone A (40) and broussochalcone B (41) were isolated from the roots of B. papyrifera (Ryu et al, 2010). These two compounds showed a dose-dependent inhibitory effect on yeast a-glucosidase.…”

Chemical compositions and bioactivities of crude polysaccharides from tea leaves beyond their useful date

“…The ␣-d-glucosidase inhibitory activity of crude TPS was determined according to the chromogenic method described by Tremblay et al with slight modifications [23]. The substrate solution p-nitrophenyl ␣-d-glucopyranoside (pNPG) was prepared with Na-phosphate buffer (0.1 mol/L, pH 6.8).…”