Potential of Polygonum cuspidatum Root as an Antidiabetic Food: Dual High-Resolution α‑Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-HRMS and NMR for Identification of Antidiabetic Constituents

The worldwide increasing incidence of type 2 diabetes has fueled an intensified search for food and herbal remedies with preventive and/or therapeutic properties. Polygonum cuspidatum Siebold & Zucc. (Polygonaceae) is used as a functional food in Japan and South Korea, and it is also a well-known traditional antidiabetic herb used in China. In this study, dual high-resolution α-glucosidase and protein-tyrosine phosphatase 1B (PTP1B) inhibition profiling was used for the identification of individual antidiabetic constituents directly from the crude ethyl acetate extract and fractions of P. cuspidatum. Subsequent preparative-scale HPLC was used to isolate a series of α-glucosidase inhibitors, which after HPLC-HRMS and NMR analysis were identified as procyanidin B2 3,3″-<i>O</i>-digallate (<b>3</b>) and (−)-epicatechin gallate (<b>5</b>) with IC₅₀ values of 0.42 ± 0.02 and 0.48 ± 0.0004 μM, respectively, as well as a series of stilbene analogues with IC₅₀ value in the range from 6.05 ± 0.05 to 116.10 ± 2.04 μM. In addition, (<i>trans</i>)-emodin-physcion bianthrone (<b>15b</b>) and (<i>cis</i>)-emodin-physcion bianthrone (<b>15c</b>) were identified as potent PTP1B inhibitors with IC₅₀ values of 2.77 ± 1.23 and 7.29 ± 2.32 μM, respectively. These findings show that P. cuspidatum is a potential functional food for management of type 2 diabetes