CYP3A4 inhibitors isolated from Licorice

The extract of licorice (Glycyrrhiza uralensis FISHER, Leguminosae) showed CYP3A4 inhibitory activity with the IC50 value of 0.022 mg/ml. Bioassay-guided purification afforded nine compounds, 3-(p-hydroxyphenyl)propionic acid (1), isoliquiritigenin (2), (3R)-vestitol (3), licopyranocoumarin (4), 4-hydroxyguaiacol apioglucoside (5), liquiritin (6), liquiritigenin 7,4'-diglucoside (7), liquiritin apioside (8), and glucoliquiritin apioside (9). Among these compounds, 3, 7, and 5 showed potent CYP3A4 inhibitory activities with IC50 values of 3.6, 17, and 20 microM, respectively. Glycyrrhizin (10), a main constituent of licorice, however, was inactive for CYP3A4 inhibition.