Isolation of CYP3A4 Inhibitors from the Black Cohosh (Cimicifuga racemosa).

Recent investigation on drug interaction has shown that some foods and herbal medicines increase the oral availability of a variety of CYP3A4 substrates, which is caused by the reduction of CYP3A4 in intestinal epithelium. During the course of our investigation on CYP3A4 interaction, we found that the commercially available dietary supplement made from black cohosh (Cimicifuga racemosa) showed CYP3A4 inhibition. Black cohosh has been used for the treatment of menopausal and post-menopausal symptoms as a dietary supplement. Bioassay-guided isolation from the supplement afforded six active principles, which were identified as cycloartanoid triterpene glycosides.

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.

Isolation of cytochrome P450 inhibitors from strawberry fruit, Fragaria ananassa.

A new glycoside, 2-beta-d-glucopyranosyloxy-4,6-dihydroxyisovalerophenone (3), was isolated from strawberry fruit along with kaempferol-3-beta-D-(6-O-trans-p-coumaroyl)glucopyranoside (1) and kaempferol-3-beta-D-(6-O-cis-p-coumaroyl)glucopyranoside (2). Compounds 1 and 2 inhibited activity of a drug-metabolizing enzyme, CYP3A4.