PTP1B inhibitory activity and molecular docking analysis of stilbene derivatives from the rhizomes of Rheum undulatum L.

Stilbene derivatives, the principal constituent of Rheum undulatum L., are known to have a wide range of biological activities, such as anti-allergic, anti-diabetic, antioxidant, and anti-inflammatory activities. A phytochemical study on the methanol extract of Korean rhubarb (R. undulatum L.) led to the isolation of nine stilbene derivatives (1–9) and one flavonoid (10). All structures were elucidated based on a comprehensive analysis of spectroscopic data. Compound 1 (5-methoxy-cis-rhapontigenin) was elucidated as a new compound, while compound 2 (5-methoxy-trans-rhapontigenin) was isolated from a natural source for the first time. Among the isolated compounds, stilbene derivatives (7–9) showed a strong inhibitory effect on protein tyrosine phosphatase 1B (PTP1B) with IC₅₀ values ranging from 4.25 to 6.78 μM, which was significantly higher than that of the positive control, ursolic acid (IC₅₀ = 11.34 μM). Furthermore, for the first time, kinetic analysis and molecular docking simulations were performed in order to understand the inhibition type as well as the interaction and binding mode of the active stilbenes (7–9) with PTP1B. Our results showed that the types of PTP1B inhibition were noncompetitive for ɛ-viniferin (8) and mixed for piceatannol (7) and δ-viniferin (9). Docking simulations of these stilbenes demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B.