Modulation Of Pregnane X Receptor, Cytochrome P450 Enzymes And P-Glycoprotein By Commonly Used Medicinal Plants

According to the recent surveys, approximately 70% of the people administering herbal supplements also take prescription or over the counter medications. This combination may in turn lead to changes in the efficacy or toxicity of the conventional drugs. Most of the herb-drug interactions have been reported to be caused by the effects of phytochemicals on cytochrome P450 enzymes (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR) resulting in the alteration of metabolism, absorption and distribution of conventional drugs. As part of our ongoing research on the safety evaluation of dietary supplements, we have evaluated the drug interaction potential of several commonly used medicinal plants (e.g. Aegle marmelos, Mitragyna speciosa, Dioscorea villosa, and Labisia pumila) and their constituents in terms of their activities on CYPs, P-gp, or PXR. These studies were performed using a battery of in vitro assays. Aegle marmelos extract and its furanocoumarin constituents showed potent time dependent inhibition (TDI) of CYP3A4 and reversible inhibition of CYP1A2. Mitragyna speciosa extract and its indole and oxindole alkaloids showed potent induction of PXR and a strong inhibition of P-gp. Dioscorea villosa extract and its two major steroidal saponins (diosgenin and dioscin) did not show significant inhibition of CYPs or P-gp. Labisia pumila extract and its alkyl phenol constituents inhibited CYP3A4, CYP2C9 and CYP2C19 while the inhibition of P-gp and PXR was shown by the extract and its saponin constituents. Early screening of the drug interaction potential of herbal supplements and their constituents may provide useful information that will help in selecting potential candidates for further studies in more clinically relevant systems.

Acknowledgements: This study is supported by The United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58-6408-1-603-04-07 and the Food and Drug Administration "Science Based Authentication of Dietary Supplements" award number 1U01FD00424605.