The inhibitory effects of beta-caryophyllene, beta-caryophyllene oxide and alpha-humulene on the activities of the main drug-metabolizing enzymes in rat and human liver in vitro

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F17%3A10364336" target="_blank" >RIV/00216208:11160/17:10364336 - isvavai.cz</a>

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S000927971730491X" target="_blank" >http://www.sciencedirect.com/science/article/pii/S000927971730491X</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.cbi.2017.10.021" target="_blank" >10.1016/j.cbi.2017.10.021</a>

Result language

angličtina

Original language name

The inhibitory effects of beta-caryophyllene, beta-caryophyllene oxide and alpha-humulene on the activities of the main drug-metabolizing enzymes in rat and human liver in vitro

Original language description

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 beta-caryophyllene (CAR), beta-caryophyllene oxide (CAO) and alpha-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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centre of drug-dietary supplements interactions and nutrigenetics</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Chemico-Biological Interactions

ISSN

0009-2797

e-ISSN

—

Volume of the periodical

278

Issue of the periodical within the volume

4

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

6

Pages from-to

123-128

UT code for WoS article

000418302000015

EID of the result in the Scopus database

2-s2.0-85032461912