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Article

Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver

1
Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, 500 05 Hradec Králové, Czech Republic
3
Department of General Surgery, Third Faculty of Medicine and University Hospital Královské Vinohrady, Charles University, 100 34 Prague, Czech Republic
4
Department of Surgery, University Hospital Hradec Králové, 500 05 Hradec Králové, Czech Republic
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(18), 4562; https://doi.org/10.3390/ijms20184562
Received: 13 August 2019 / Revised: 11 September 2019 / Accepted: 12 September 2019 / Published: 14 September 2019
(This article belongs to the Special Issue Terpenes and Essential Oils: Health Risks and Benefits)
Sesquiterpenes, the main components of plant essential oils, are bioactive compounds with numerous health-beneficial activities. Sesquiterpenes can interact with concomitantly administered drugs due to the modulation of drug-metabolizing enzymes (DMEs). The aim of this study was to evaluate the modulatory effects of six sesquiterpenes (farnesol, cis-nerolidol, trans-nerolidol, α-humulene, β-caryophyllene, and caryophyllene oxide) on the expression of four phase I DMEs (cytochrome P450 3A4 and 2C, carbonyl reductase 1, and aldo-keto reductase 1C) at both the mRNA and protein levels. For this purpose, human precision-cut liver slices (PCLS) prepared from 10 patients and transfected HepG2 cells were used. Western blotting, quantitative real-time PCR and reporter gene assays were employed in the analyses. In the reporter gene assays, all sesquiterpenes significantly induced cytochrome P450 3A4 expression via pregnane X receptor interaction. However in PCLS, their effects on the expression of all the tested DMEs at the mRNA and protein levels were mild or none. High inter-individual variabilities in the basal levels as well as in modulatory efficacy of the tested sesquiterpenes were observed, indicating a high probability of marked differences in the effects of these compounds among the general population. Nevertheless, it seems unlikely that the studied sesquiterpenes would remarkably influence the bioavailability and efficacy of concomitantly administered drugs. View Full-Text
Keywords: sesquiterpene; mRNA expression; protein expression; precision-cut liver slices; gene reporter assay; cytochrome P450 3A4; pregnane X receptor sesquiterpene; mRNA expression; protein expression; precision-cut liver slices; gene reporter assay; cytochrome P450 3A4; pregnane X receptor
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MDPI and ACS Style

Šadibolová, M.; Zárybnický, T.; Smutný, T.; Pávek, P.; Šubrt, Z.; Matoušková, P.; Skálová, L.; Boušová, I. Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver. Int. J. Mol. Sci. 2019, 20, 4562. https://doi.org/10.3390/ijms20184562

AMA Style

Šadibolová M, Zárybnický T, Smutný T, Pávek P, Šubrt Z, Matoušková P, Skálová L, Boušová I. Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver. International Journal of Molecular Sciences. 2019; 20(18):4562. https://doi.org/10.3390/ijms20184562

Chicago/Turabian Style

Šadibolová, Michaela, Tomáš Zárybnický, Tomáš Smutný, Petr Pávek, Zdeněk Šubrt, Petra Matoušková, Lenka Skálová, and Iva Boušová. 2019. "Sesquiterpenes Are Agonists of the Pregnane X Receptor but Do Not Induce the Expression of Phase I Drug-Metabolizing Enzymes in the Human Liver" International Journal of Molecular Sciences 20, no. 18: 4562. https://doi.org/10.3390/ijms20184562

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