Essential oils of culinary herbs and spices activate PXR and induce CYP3A4 in human intestinal and hepatic in vitro models
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
30071242
DOI
10.1016/j.toxlet.2018.07.023
PII: S0378-4274(18)31510-8
Knihovny.cz E-resources
- Keywords
- Cytochrome P450, Essential oils, Food-drug interactions, Human hepatocytes, Xenobiotics,
- MeSH
- Transcriptional Activation drug effects MeSH
- Cell Line MeSH
- Cytochrome P-450 CYP3A biosynthesis MeSH
- Cytochrome P-450 CYP2B6 biosynthesis genetics MeSH
- Enzyme Induction drug effects MeSH
- Hepatocytes drug effects MeSH
- Liver drug effects metabolism MeSH
- Spices analysis MeSH
- Humans MeSH
- Oils, Volatile pharmacology MeSH
- ATP Binding Cassette Transporter, Subfamily B biosynthesis MeSH
- Pregnane X Receptor MeSH
- Primary Cell Culture MeSH
- Genes, Reporter MeSH
- Receptors, Steroid drug effects metabolism MeSH
- Intestines drug effects MeSH
- Intestinal Mucosa metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- ABCB1 protein, human MeSH Browser
- CYP2B6 protein, human MeSH Browser
- CYP3A4 protein, human MeSH Browser
- Cytochrome P-450 CYP3A MeSH
- Cytochrome P-450 CYP2B6 MeSH
- Oils, Volatile MeSH
- ATP Binding Cassette Transporter, Subfamily B MeSH
- Pregnane X Receptor MeSH
- Receptors, Steroid MeSH
Essential oils (EOs) are extensively used in food industry, gastronomy and alternative medicine. They are multicomponent mixtures of bioactive compounds; hence, their potential for food-drug interactions is substantial. In this study, we investigated the effects of 31 EOs of culinary herbs and spices on the transcriptional activity of pregnane X receptor (PXR) and expression of cytochrome P450 3A4 (CYP3A4), using human intestinal and hepatic in vitro models. All tested EOs activated PXR in intestinal LS180 cells transiently transfected with PXR, as revealed by a reporter gene assay. Consistently, all EOs induced CYP3A4 mRNA expression in PXR-transfected LS180 cells, primary human hepatocytes and wild-type hepatic progenitor HepaRG cells. EO-mediated induction of CYP3A4 mRNA expression was nullified in PXR-knock out HepaRG cells, suggesting the involvement of PXR in these effects. Collectively, we showed that EOs of culinary herbs and spices might be common activators of PXR and inducers of CYP3A4 at doses present in foods, thereby, they might have a potential for food-drug interactions. Follow-up studies are warranted to identify the bioactive constituents in the tested EOs.
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