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Nguyen, Dinh-Tuan; To, Dao-Cuong; Tran, Thi-Tuyen; Tran, Manh-Hung; Nguyen, Phi-Hung
Journal of natural medicines, 2021/1, Letnik: 75, Številka: 1Journal Article
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 plant Selaginella rolandi-principis . The chemical structures of the isolates were elucidated by extensive analysis of spectroscopic and physicochemical data. Compounds 3 ‒ 5 have been identified from Selaginella genus 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 α-glucosidase enzyme activities as well. Compounds 1 exhibited the most potency with inhibitory IC 50 values of 7.40 ± 0.28 and 7.52 ± 0.37 µM against PTP1B and α-glucosidase, respectively. Compounds 3 and 5 possessed potential inhibitions on PTP1B enzyme with IC 50 values of 23.02 ± 1.29 and 11.08 ± 0.92 µM and moderate inhibitions on α-glucosidase with IC 50 values of 36.47 ± 1.87 and 55.73 ± 2.58 µM, respectively. Compounds 2 and 4 showed weak PTP1B inhibitory activity (IC 50 > 30 µM) but displayed remarkable α-glucosidase inhibition with IC 50 values of 3.39 ± 0.87 and 9.72 ± 0.62 µM, respectively. Furthermore, ursolic acid as a positive control (IC 50 3.42 ± 0.26 µM) and compounds 1 and 5 acted as mixed-competitive inhibitors against PTP1B enzyme with K i values of 6.46, 10.28, and 15.01 µM, respectively. In addition, compounds 1 and 5 also showed potent stimulatory effects on 2-NBDG uptake at a concentration of 10 µM. The obtained result might suggest the potential of new coumarin ( 1 ) as a new type of natural PTP1B and α-glucosidase inhibitor for further research and development of antidiabetic and obese agents. Graphic abstract
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