PXR as a mediator of herbedrug interaction

Brett C. Hogle a, Xiudong Guan b, M. Maggie Folan a, Wen Xie a,c,d,*

a Pharmaceutical Sciences Graduate Program, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA

b Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

c Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA,

USA

d Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA

Medicinal herbs have been a part of human medicine for thousands of years. The herb edrug interaction is an extension of drugedrug interaction, in which the consumptions of herbs cause alterations in the metabolism of drugs the patients happen to take at the same time. The pregnane X receptor (PXR) has been established as one of the most important transcriptional factors that regulate the expression of phase I enzymes, phase II enzymes, and drug transporters in the xenobiotic responses. Since its initial discovery, PXR has been implicated in multiple herbedrug interactions that can lead to alterations of the drug's pharmacokinetic properties and cause fluctuating therapeutic efficacies, possibly leading to complications. Regions of the world that heavily incorporate herbalism into their primary health care and people turning to alternative medicines as a personal choice could be at risk for adverse reactions or unintended results from these interactions. This article is intended to highlight our understanding of the PXR-mediated herbedrug interactions.

Keywords: Drug metabolism, Herb-drug interaction, PXR, St. John's Wort, Xenobiotics