No abstract

Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1–8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1–5) and dihydroflavonols (6–8). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC50 = 1.9–8.2 μM) than α-glucosidase (IC50 = 2.2–78.9 μM). Mimulone (1) was the most effective against PTP1B with IC50 = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (8) displayed potent inhibition against α-glucosidase (IC50 = 2.2 μM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in Vmax, an increase of Km, and Kik/Kiv ratio ranging between 2.66 and 3.69.

The roots of Broussonetia papyrifera were extracted into four different polar solvents: chloroform, 50% ethanol in water, ethanol, and water. The ethanol extract showed the most potent inhibition (72.3% at 20 g/mL) against xanthine oxidase (XOD). Chromatography of EE yielded nine phenolic phytochemicals, which were confirmed as broussochalcone A (1), broussochalcone B (2), 3,4-dihydroxyisolonchocarpin (3), 4-hydroxyisolonchocarpin (4), 3-'(3-methylbut-2-enyl)-3',4',7-trihydroxyflavane (5), kazinol A (6), kazinol B (7), kazinol E (8), and broussoflavan A (9). All isolated compounds (19) possessed potent antioxidant activities against 2,2-diphenyl-l-picrylhydrazyl and 2,2'-azino-bis-ethylbenzthiazoline-6-sulfonic acid (ABTS) radicals with IC 50 values ranging from 5.8 to 252.8 M. Although most compounds exhibited potent inhibition with IC 50 values ranging 0.6-164 M against XOD, compounds 1 and 3 were found to be the principal contributors to the XOD inhibition in ethanol extract. The analysis of K I and K IS values proved that the two most promising compounds (1 and 3), present at high concentrations in the root barks as analyzed by using high-performance liquid chromatography analysis, were reversible mixed type I inhibitors.

A yellow resin (gamboge) from Garcinia hanburyi has been widely used as folk medicine due to its antibacterial and antitumor activities. We isolated four α-glucosidase inhibitory compounds from the methanol extract of gamboge. The compounds (1-4) were identified as gambogoic acid (1), moreollic acid (2), gambogic acid (3), and 10-methoxygambogenic acid (4), respectively through spectroscopic data including 2D-NMR and HREIMS. All compounds were examined in the enzyme inhibition assay against α-glucosidase to identify their inhibitory potencies and kinetic behavior. All compounds (1-4) showed enzyme inhibition against α-glucosidase, but the activity was significantly affected by the methoxy group on C-10 of ring A and pentenyl pyran moiety of ring D. For example, compound 1 (IC 50 =41.4 μM) bearing pyran ring eight times effective that 4 (IC 50 =350.6 μM) having geranyl group itself. Most active compound was found out to be gambogoic acid (1) which was analyzed most abundant metabolite in gamboge by LC-ESI-MS/MS. In kinetic study, compounds 1 and 2 were proved as noncompetitive inhibitors.