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
Language English Country Ireland Media print-electronic
Document type Journal Article
PubMed
29074051
DOI
10.1016/j.cbi.2017.10.021
PII: S0009-2797(17)30491-X
Knihovny.cz E-resources
- Keywords
- Drug-sesquiterpene interactions, Enzyme inhibition, Sesquiterpenes, cytochromes P450,
- MeSH
- Anti-Inflammatory Agents, Non-Steroidal chemistry metabolism MeSH
- Cytochrome P-450 CYP1A2 chemistry metabolism MeSH
- Cytochrome P-450 CYP3A chemistry metabolism MeSH
- Inhibitory Concentration 50 MeSH
- Microsomes, Liver enzymology MeSH
- Liver enzymology MeSH
- Kinetics MeSH
- Rats MeSH
- Humans MeSH
- Monocyclic Sesquiterpenes MeSH
- Polycyclic Sesquiterpenes MeSH
- Rats, Wistar MeSH
- Sesquiterpenes chemistry metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Inflammatory Agents, Non-Steroidal MeSH
- caryophyllene oxide MeSH Browser
- caryophyllene MeSH Browser
- Cytochrome P-450 CYP1A2 MeSH
- Cytochrome P-450 CYP3A MeSH
- humulene MeSH Browser
- Monocyclic Sesquiterpenes MeSH
- Polycyclic Sesquiterpenes MeSH
- Sesquiterpenes 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.
References provided by Crossref.org
In Vitro Interaction of Binuclear Copper Complexes with Liver Drug-Metabolizing Cytochromes P450
