Beta-caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4-In Vitro and In Silico Studies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F19%3A10408261" target="_blank" >RIV/00216208:11160/19:10408261 - isvavai.cz</a>

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MsbtB6ixLg" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=MsbtB6ixLg</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.934323" target="_blank" >10.33549/physiolres.934323</a>

Result language

angličtina

Original language name

Beta-caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4-In Vitro and In Silico Studies

Original language description

Evaluation of possible interactions with enzymes of drug metabolism is an important part of studies on safety and, in general, on the properties of any drug or biologically active compound. Here, focus is given on interactions of three sesquiterpenes (beta-caryophyllene oxide (CAO), trans-nerolidol (tNER) and farnesol (FAR)) with CYP3A4. To determine the CYP3A4 activity, specific substrates testosterone (TES) and midazolam (MDZ) were used. In human liver microsomes, the CAO inhibited the MDZ 1&apos;-hydroxylation by mixed type inhibition and K-i 46.6 mu M; TES 6 beta-hydroxylation was inhibited more strongly by tNER by the same mechanism and with K-i of 32.5 mu M. Results indicated a possibility of different mode of interaction of both compounds within the active site of CYP3A4 and this was why the molecular docking study was done. The docking experiments showed that the studied sesquiterpenes (CAO and tNER) bound to the CYP3A4 active site cause a significant decrease of binding affinity of substrates tested which corresponded well to the inhibition studies. The inhibition observed, however, most probably does not pose a real harm to microsomal drug metabolism as the levels of sesquiterpenes in plasma (assuming the use of these compounds as spices or flavoring additives) does not usually exceed micromolar range. Hence, the interaction of drugs metabolized by CYP3A4 with sesquiterpenes is less probable.

Czech name

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Czech description

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Type

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

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

—

Volume of the periodical

68

Issue of the periodical within the volume

Suppl. 1

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

8

Pages from-to

"S51"-"S58"

UT code for WoS article

000499085100006

EID of the result in the Scopus database

2-s2.0-85075453864