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The pregnane X receptor (PXR, NR1I2) is a member of the nuclear receptor superfamily that is activated by a myriad of clinically used compounds and natural products. Activation of PXR in liver regulates the expression genes encoding proteins that are intimately involved in the hepatic uptake, metabolism, and elimination of toxic compounds from our bodies. PXR-mediated herb-drug interactions can have undesirable effects in patients receiving combination therapy. This can be especially important in cancer patients who self-administer over-the-counter herbal remedies together with conventional anticancer chemotherapeutics. Tian xian is a traditional Chinese herbal anticancer remedy that activates human PXR in cell-based reporter gene assays. Moreover, tian xian alters the strength of interaction between the human PXR protein and transcriptional cofactor proteins. A novel line of humanized PXR mice are described and used here to show that tian xian increases expression of Cyp3a11 in primary cultures of rodent hepatocytes. Tian xian also induces expression of CYP3A4 in primary cultures of human hepatocytes. Taken together, these data indicate that coadministration of tian xian is probably contraindicated in patients undergoing anticancer therapy with conventional chemotherapeutic agents. These data are of particular importance due to the fact that this herbal remedy is currently marketed as an adjunct therapy that reduces the side effects of conventional chemotherapy and is available without a prescription. Future studies should be conducted to determine the extent to which coadministration of this Chinese herbal remedy alters the pharmacokinetic and pharmacodynamic properties of conventional anticancer therapy.

The Traditional Chinese Herbal Remedy Tian Xian Activates Pregnane X Receptor and Induces CYP3A Gene Expression in Hepatocytes