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.

• Klíčová slova
• cytochrome P450 3A4, gene reporter assay, mRNA expression, precision-cut liver slices, pregnane X receptor, protein expression, sesquiterpene,
• MeSH
• aldo-keto reduktasy metabolismus   MeSH
• buňky Hep G2 MeSH
• cytochrom P-450 CYP3A metabolismus   MeSH
• farnesol farmakologie   MeSH
• hepatocyty metabolismus   MeSH
• játra enzymologie   MeSH
• karbonylreduktasa (NADPH) metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• metabolická clearance MeSH
• monocyklické seskviterpeny farmakologie   MeSH
• polycyklické seskviterpeny farmakologie   MeSH
• pregnanový X receptor agonisté   metabolismus   MeSH
• receptory aromatických uhlovodíků agonisté   metabolismus   MeSH
• rodina 2 cytochromů P450 metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• seskviterpeny farmakologie   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldo-keto reduktasy MeSH
• caryophyllene oxide MeSH Prohlížeč
• caryophyllene MeSH Prohlížeč
• cytochrom P-450 CYP3A MeSH
• cytochrome P-450 CYP2C subfamily MeSH Prohlížeč
• farnesol MeSH
• humulene MeSH Prohlížeč
• karbonylreduktasa (NADPH) MeSH
• messenger RNA MeSH
• monocyklické seskviterpeny MeSH
• nerolidol MeSH Prohlížeč
• polycyklické seskviterpeny MeSH
• pregnanový X receptor MeSH
• receptory aromatických uhlovodíků MeSH
• rodina 2 cytochromů P450 MeSH
• seskviterpeny MeSH
• systém (enzymů) cytochromů P-450 MeSH