Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1.
Article Details
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Wang YM, Lin W, Chai SC, Wu J, Ong SS, Schuetz EG, Chen T
Piperine activates human pregnane X receptor to induce the expression of cytochrome P450 3A4 and multidrug resistance protein 1.
Toxicol Appl Pharmacol. 2013 Oct 1;272(1):96-107. doi: 10.1016/j.taap.2013.05.014. Epub 2013 May 22.
- PubMed ID
- 23707768 [ View in PubMed]
- Abstract
Activation of the pregnane X receptor (PXR) and subsequently its target genes, including those encoding drug transporters and metabolizing enzymes, while playing substantial roles in xenobiotic detoxification, might cause undesired drug-drug interactions. Recently, an increased awareness has been given to dietary components for potential induction of diet-drug interactions through activation of PXR. Here, we studied, whether piperine (PIP), a major component extracted from the widely-used daily spice black pepper, could induce PXR-mediated expression of cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1). Our results showed that PIP activated human PXR (hPXR)-mediated CYP3A4 and MDR1 expression in human hepatocytes, intestine cells, and a mouse model; PIP activated hPXR by recruiting its coactivator SRC-1 in both cellular and cell-free systems; PIP bound to the hPXR ligand binding domain in a competitive ligand binding assay in vitro. The dichotomous effects of PIP on induction of CYP3A4 and MDR1 expression observed here and inhibition of their activity reported elsewhere challenges the potential use of PIP as a bioavailability enhancer and suggests that caution should be taken in PIP consumption during drug treatment in patients, particularly those who favor daily pepper spice or rely on certain pepper remedies.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Piperine Nuclear receptor subfamily 1 group I member 2 Protein Humans UnknownNot Available Details - Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Piperine Investigational ABCB1 5243 upregulated piperine results in increased expression of ABCB1 mRNA 7q21.12 Piperine Investigational CYP3A4 1576 upregulated piperine results in increased expression of CYP3A4 mRNA 7q22.1 Rifampicin Approved ABCB1 5243 upregulated Rifampin results in increased expression of ABCB1 mRNA 7q21.12 Rifampicin Approved CYP3A4 1576 upregulated Rifampin results in increased expression of CYP3A4 mRNA 7q22.1 - Pharmaco-proteomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Rifampicin Approved CYP3A4 1576 increased Rifampin results in increased expression of CYP3A4 protein 7q22.1 Rifampicin Approved CYP3A4 1576 increased Rifampin results in increased expression of CYP3A4 protein 7q22.1 Rifampicin Approved CYP3A4 1576 increased Rifampin results in increased expression of CYP3A4 protein 7q22.1 Rifampicin Approved ABCB1 5243 increased Rifampin results in increased expression of ABCB1 protein 7q21.12