PTP1B and α-glucosidase inhibitory activities of the chemical constituents from Hedera rhombea fruits: Kinetic analysis and molecular docking simulation

In this study, we present the first investigation of Hedera rhombea Bean fruit, which led to the isolation of six undescribed compounds including two megastigmane glucosides, two rare 1,4-dioxane neolignanes, and two quinic acid derivatives, together with 26 known compounds. Their structures and absolute configurations were elucidated by extensive analysis of NMR spectroscopic data, HRMS, and ECD calculations. This is the first report on the isolation of methyl 3-O-caffeoyl-5-O-p-coumaroylquinate from a natural source. Among the isolated compounds, falcarindiol and caffeoyltryptophan showed significant PTP1B inhibition with IC₅₀ values of 7.32 and 16.99 μM, respectively, compared to those of the positive controls [sodium orthovanadate (IC₅₀ = 17.96 μM) and ursolic acid (IC₅₀ = 4.53 μM)]. These two compounds along with several other compounds displayed significant α-glucosidase inhibitions with IC₅₀ values ranging from 12.88 to 91.89 μM, stronger than that of the positive control (acarbose, IC₅₀ = 298.07 μM). Enzyme kinetic analysis indicated that caffeoyltryptophan and falcarindiol displayed competitive and mixed-type PTP1B inhibition, respectively, whereas the α-glucosidase inhibition type was mixed-type for caffeoyltryptophan and uncompetitive (rarely reported for a-glucosidase inhibitors) for falcarindiol. In addition, molecular docking results showed that these active compounds exhibited good binding affinities toward both PTP1B and α-glucosidase with negative binding energies. The results of the present study demonstrate that these active compounds might be beneficial in the treatment of type 2 diabetes.

1,4-Dioxane neolignanes; Araliaceae; Hedera rhombea; Megastigmane glucosides; Molecular docking; PTP1B; α-Glucosidase.