Natural PTP1B Inhibitors From Polygonum cuspidatum and Their 2-NBDG Uptake Stimulation

Abstract

Ten active principles (compounds 1-10) have been isolated following protein tyrosine phosphatase 1B (PTP1B) assay-guided fractionation of the methanol extract of the root of Polygonum cuspidatum. The chemical structures of the compounds were characterized mainly by nuclear magnetic resonance (NMR) spectroscopic and physicochemical data. This is the first time that 9,10-anthraquinones (compounds 5-6) have been isolated from P. cuspidatum, and this is the first record of compound 9 from the genus Polygonum. Except for compound 4, all the isolates showed potential inhibitory activity against PTP1B with half-maximal inhibitory concentration IC50 values ranging from 6.3 to 28.9 µM. Furthermore, a kinetic study indicated mixed-competitive inhibition with PTP1B for compounds 2 and 9 and noncompetitive inhibition for compounds 3 and 6. In addition, compounds 2, 3, 6, and 9 also induced the 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-d-glucose uptake stimulation in 3T3-L1 adipocytes at concentrations of 10 and 5 µM. Taken together, the results reveal that P. cuspidatum could be a new source of natural compounds for further research and development of antidiabetic agents.