Hepatotoxicity of Herbal Supplements Mediated by Modulation of Cytochrome P450.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Herb-Drug Interactions*; Chemical and Drug Induced Liver Injury/*etiology ; Cytochrome P-450 Enzyme Inhibitors/*pharmacology ; Cytochrome P-450 Enzyme System/*metabolism ; Dietary Supplements/*toxicity ; Liver/*drug effects ; Xenobiotics/*metabolism; Animals ; Constitutive Androstane Receptor ; Humans ; Liver/pathology ; Mice ; Pregnane X Receptor ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Steroid/metabolism ; United States ; United States Food and Drug Administration

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.
Competing Interests: The authors declare no conflict of interest.

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F31 DK116523 United States DK NIDDK NIH HHS; P30 CA021765 United States CA NCI NIH HHS; R35 GM118041 United States GM NIGMS NIH HHS

Keywords: constitutive androstane receptor; cytochrome P450; drug-drug interactions; drug-herb interactions; drug-induced liver injury; herb-herb interactions; herb-induced liver injury; herbal supplement; pregnane X receptor; xenobiotic metabolism

0 (Constitutive Androstane Receptor)
0 (Cytochrome P-450 Enzyme Inhibitors)
0 (Pregnane X Receptor)
0 (Receptors, Cytoplasmic and Nuclear)
0 (Receptors, Steroid)
0 (Xenobiotics)
9035-51-2 (Cytochrome P-450 Enzyme System)

Date Created: 20171109 Date Completed: 20180709 Latest Revision: 20211204

20240829

PMC5713322

10.3390/ijms18112353

29117101