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Int. J. Mol. Sci. 2017, 18(11), 2353; https://doi.org/10.3390/ijms18112353

Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450

1
Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
2
Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, USA
*
Author to whom correspondence should be addressed.
Received: 26 September 2017 / Revised: 3 November 2017 / Accepted: 3 November 2017 / Published: 8 November 2017
(This article belongs to the Special Issue Hepatotoxicity: Molecular Mechanisms and Pathophysiology)
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Abstract

Herbal supplements are a significant source of drug-drug interactions (DDIs), herb-drug interactions, and hepatotoxicity. Cytochrome P450 (CYP450) enzymes metabolize a large number of FDA-approved pharmaceuticals and herbal supplements. This metabolism of pharmaceuticals and supplements can be augmented by concomitant use of either pharmaceuticals or supplements. The xenobiotic receptors constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) can respond to xenobiotics by increasing the expression of a large number of genes that are involved in the metabolism of xenobiotics, including CYP450s. Conversely, but not exclusively, many xenobiotics can inhibit the activity of CYP450s. Induction of the expression or inhibition of the activity of CYP450s can result in DDIs and toxicity. Currently, the United States (US) Food and Drug Administration does not require the investigation of the interactions of herbal supplements and CYP450s. This review provides a summary of herbal supplements that inhibit CYP450s, induce the expression of CYP450s, and/or whose toxicity is mediated by CYP450s. View Full-Text
Keywords: cytochrome P450; pregnane X receptor; constitutive androstane receptor; herbal supplement; drug-induced liver injury; herb-induced liver injury; drug-drug interactions; drug-herb interactions; herb-herb interactions; xenobiotic metabolism cytochrome P450; pregnane X receptor; constitutive androstane receptor; herbal supplement; drug-induced liver injury; herb-induced liver injury; drug-drug interactions; drug-herb interactions; herb-herb interactions; xenobiotic metabolism
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Brewer, C.T.; Chen, T. Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450. Int. J. Mol. Sci. 2017, 18, 2353.

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