Prenylated Phenolic Compounds from the Aerial Parts of Glycyrrhiza uralensis as PTP1B and α-Glucosidase Inhibitors

Glycyrrhiza uralensis (liquorice) is a well-known medicinal plant. Its roots and rhizomes are used as the popular Chinese herbal medicine Gan-Cao. An ethanol extract of the aerial parts of G. uralensis showed antidiabetic effects on db/db mice. It decreased the blood glucose level by 30.3% and increased the serum insulin level by 41.8% compared to the control group. Eighty-six phenolic compounds (1-86) were obtained from the aerial parts, including the new prenylated isoflavanones (1-5), isoflavans (69), and a 2-phenylbenzofuran (10). The structures were identified by NMR and HRESIMS data analyses, and the absolute configurations were established by comparing the calculated and experimental ECD spectroscopic data. Compounds 2, 6, and 10 inhibited PTP1B with IC50 values of 5.9, 6.7, and 5.3 mu M, respectively. Compound 2 and the known compounds glycycoumarin (76) and glyurallin A (79) inhibited alpha-glucosidase with IC50 values of 20.1, 0.1, and 0.3 mu M, respectively. Compound 4 at 10 mu M increased the glucose uptake rate to 95% in an insulin resistance HepG2 cell model (p < 0.01).