In vitro and in silico Analysis of PTP1B and α-Glucosidase Inhibitory Activities of Isoflavonoids Isolated from Belamcanda chinensis Roots

초록

Type 2 diabetes (T2D) is currently the most prevalent form of diabetes and an expanding global health problem. α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) are well-known as the promising target enzymes for the treatment of T2D. In our continuing search for new antidiabetic substances from Korean medicinal plants, twelve isoflavonoids and four flavonoids were isolated and structurally determined from the roots of Belamcanda chinensis, and their α-glucosidase and PTP1B inhibitory activities were investigated in vivo and in silico. The results showed that two isoflavonoids (irilin D and genistein) act as dual α-glucosidase and PTP1B inhibitors: moderately inhibited PTP1B [irilin D (IC50 = 31.86 µM) and genistein (IC50 = 24.64 µM)] and significantly inhibited α-glucosidase [irilin D (IC50 = 44.22 µM) and genistein (IC50 = 14.71 µM)] in comparison to the positive controls, ursolic acid (IC50 = 5.99 µM) and acarbose (IC50 = 216.30 µM), respectively. To the best of our knowledge, this is the first investigation on the inhibitory activity of irilin D against PTP1B and α-glucosidase enzymes. The kinetic investigation of irilin D indicated its noncompetitive inhibition type for both of these two enzymes. In addition, molecular docking results showed that irilin D exhibited good binding affinities toward both PTP1B and α-glucosidase with negative binding energies. The results suggested the potential of B. chinensis isoflavonoids in the prevention and treatment of T2D.

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