PTP1B and α-glucosidase inhibitors from Selaginella rolandi-principis and their glucose uptake stimulation

As part of an ongoing search for new protein tyrosine phosphatase 1B inhibitors and glucose uptake stimulators from nature, a new coumarin, selaginolide A (1) and four known isoflavones (2-5) were isolated from the ethanol extract of a Vietnamese medicinal plantSelaginella rolandi-principis. The chemical structures of the isolates were elucidated by extensive analysis of spectroscopic and physicochemical data. Compounds3-5have been identified fromSelaginellagenus for the first time. The antidiabetic properties of the isolates (1-5) were investigated using in vitro assay on 2-NBDG uptake in 3T3-L1 adipocytes and against PTP1B and alpha-glucosidase enzyme activities as well. Compounds1exhibited the most potency with inhibitory IC50 values of 7.40 +/- 0.28 and 7.52 +/- 0.37 mu M against PTP1B and alpha-glucosidase, respectively. Compounds3and5possessed potential inhibitions on PTP1B enzyme with IC(50)values of 23.02 +/- 1.29 and 11.08 +/- 0.92 mu M and moderate inhibitions on alpha-glucosidase with IC(50)values of 36.47 +/- 1.87 and 55.73 +/- 2.58 mu M, respectively. Compounds 2 and 4 showed weak PTP1B inhibitory activity (IC50 > 30 mu M) but displayed remarkable alpha-glucosidase inhibition with IC(50)values of 3.39 +/- 0.87 and 9.72 +/- 0.62 mu M, respectively. Furthermore, ursolic acid as a positive control (IC50 3.42 +/- 0.26 mu M) and compounds1and5acted as mixed-competitive inhibitors against PTP1B enzyme withK(i)values of 6.46, 10.28, and 15.01 mu M, respectively. In addition, compounds 1 and 5 also showed potent stimulatory effects on 2-NBDG uptake at a concentration of 10 mu M. The obtained result might suggest the potential of new coumarin (1) as a new type of natural PTP1B and alpha-glucosidase inhibitor for further research and development of antidiabetic and obese agents. [GRAPHICS] .