The inhibitory effects of β-caryophyllene, β-caryophyllene oxide and α-humulene on the activities of the main drug-metabolizing enzymes in rat and human liver in vitro
Jazyk angličtina Země Irsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
29074051
DOI
10.1016/j.cbi.2017.10.021
PII: S0009-2797(17)30491-X
Knihovny.cz E-zdroje
- Klíčová slova
- Drug-sesquiterpene interactions, Enzyme inhibition, Sesquiterpenes, cytochromes P450,
- MeSH
- antiflogistika nesteroidní chemie metabolismus MeSH
- cytochrom P-450 CYP1A2 chemie metabolismus MeSH
- cytochrom P-450 CYP3A chemie metabolismus MeSH
- inhibiční koncentrace 50 MeSH
- jaterní mikrozomy enzymologie MeSH
- játra enzymologie MeSH
- kinetika MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- monocyklické seskviterpeny MeSH
- polycyklické seskviterpeny MeSH
- potkani Wistar MeSH
- seskviterpeny chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiflogistika nesteroidní MeSH
- caryophyllene oxide MeSH Prohlížeč
- caryophyllene MeSH Prohlížeč
- cytochrom P-450 CYP1A2 MeSH
- cytochrom P-450 CYP3A MeSH
- humulene MeSH Prohlížeč
- monocyklické seskviterpeny MeSH
- polycyklické seskviterpeny MeSH
- seskviterpeny MeSH
Sesquiterpenes, the main components of plant essential oils, are often taken in the form of folk medicines and dietary supplements. Several sesquiterpenes possess interesting biological activities but they could interact with concurrently administered drugs via inhibition of drug-metabolizing enzymes. Therefore, the present study was designed to test the potential inhibitory effect of tree structurally relative sesquiterpenes β-caryophyllene (CAR), β-caryophyllene oxide (CAO) and α-humulene (HUM) on the activities of the main drug-metabolizing enzymes. For this purpose, rat and human hepatic subcellular fractions were incubated with CAR, CAO or HUM together with specific substrates for oxidation, reduction and conjugation enzymes and their coenzymes. HPLC, spectrophotometric and spectrofluorimetric analyses of product formations were used. All tested sesquiterpenes significantly inhibited cytochromes P4503A (CYP3A) activities in rats as well as in human hepatic microsomes, with CAO being the strongest inhibitor. A non-competitive type of inhibition was found. On the other hand, none of the tested sesquiterpenes significantly affected the activities of carbonyl-reducing enzymes (CBR1, AKRs, NQO1) or conjugation enzymes (UGTs, GSTs, SULTs, COMT). As CYP3A enzymes metabolize many drugs, their inhibition by CAO, CAR and HUM might affect the pharmacokinetics of concurrently administered drugs. Similar results obtained in rat and human hepatic microsomes indicate that rats could be used for further testing of possible drug-sesquiterpenes interactions in vivo.
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