Safety of botanical dietary supplements used by menopausal women: In vitro investigations of drug-botanical interactions

As women are using botanical dietary supplements as alternatives to conventional estrogen replacement therapy, it is important to understand the potential of these supplements to interact with clinically used drugs. Drug-botanical interactions can include inhibition and induction of drug metabolizing enzymes, especially the cytochrome P450 enzymes, and induction or inhibition of drug transporters. To facilitate these studies, we developed high-throughput assays using incubations of human liver microsomes with cocktails of probe substrates for specific enzymes followed by quantitative analysis of enzymatic products using UHPLC-MS/MS. Thus far, we have investigated drug-botanical interactions in vitro for standardized extracts of red clover (Trifolium pratense), hops (Humulus lupulus) and licorice (Glycyrrhiza glabra), which are popular botanical dietary supplements used by menopausal women. For example, the hop extract showed significant inhibition of CYP1A2, CYP2C8, CYP2C9 and CYP2C19, which was attributed primarily to the prenylated hop phenols including xanthohumol, isoxanthohumol 6-prenylnaringenin, and 8-prenylnaringenin. However, hops produced no induction of cytochrome P450 enzymes during incubation with human hepatocytes. In contrast, the licorice extract exhibited both inhibition and induction of several cytochrome P450 enzymes.