Herbal supplements are used worldwide for treating many ailments as well as for general health benefits. In recent years the use of herbal supplements in combination with the prescription and over-the-counter drugs is on the rise to treat multiple disease conditions which is posing an increased risk of herb drug interactions (HDI). HDI is becoming an important safety concern for many herbal supplements. Since most of the clinically relevant pharmacokinetic drug interactions are known to occur due to the modulation of the activity of drug metabolizing enzymes (CYPs) and drug transporter (P-gp), PXR-mediated induction of CYPs and P-gp has drawn considerable attention as one of the major mechanisms involved in drug interactions. St John’s Wort (Hypericum perforatum) is a well known example of the herb causing clinically relevant herb drug interactions that is mediated through PXR activation and hypericin is known to be responsible for such effect.
We have screened some commonly used herbs and their constituents for activation of PXR to predict their potential for herb drug interaction using a reporter gene assay. Their effects on the expression of major drug metabolizing enzymes (3A4, 1A2, 2C9, 2B6) and efflux transporter (P-gp) were also determined by q-PCR techniques and the enzymatic activities were measured using specific substrates for each enzyme isoform. Potent activation of PXR was observed with several herbs such as M. speciosa, E. californica, B. natalensis, and G. glabra which led to an increased expression of its target genes. Results will be discussed.
ACKNOWLEDGEMENTS This study is partially supported by The United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58-6060-6-015 and the Food and Drug Administration "Science Based Authentication of Dietary Supplements" award number 2U01FD004246-06.