β‐caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4 – In Vitro and In Silico Studies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F19%3A73596105" target="_blank" >RIV/61989592:15110/19:73596105 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15310/19:73596105

Výsledek na webu

<a href="http://www.biomed.cas.cz/physiolres/pdf/68/68_S51.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/68/68_S51.pdf</a>

DOI - Digital Object Identifier

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

Jazyk výsledku

angličtina

Název v původním jazyce

β‐caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4 – In Vitro and In Silico Studies

Popis výsledku v původním jazyce

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 (β-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´-hydroxylation by mixed type inhibition and Ki 46.6 μM; TES 6β-hydroxylation was inhibited more strongly by tNER by the same mechanism and with Ki of 32.5 μM. 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.

Název v anglickém jazyce

β‐caryophyllene Oxide and Trans-nerolidol Affect Enzyme Activity of CYP3A4 – In Vitro and In Silico Studies

Popis výsledku anglicky

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 (β-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´-hydroxylation by mixed type inhibition and Ki 46.6 μM; TES 6β-hydroxylation was inhibited more strongly by tNER by the same mechanism and with Ki of 32.5 μM. 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/LO1304" target="_blank" >LO1304: Podpora udržitelnosti Ústavu molekulární a translační medicíny</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

PHYSIOLOGICAL RESEARCH

ISSN

0862-8408

e-ISSN

—

Svazek periodika

68

Číslo periodika v rámci svazku

Suppl 1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

8

Strana od-do

"S51"-"S58"

Kód UT WoS článku

000499085100006

EID výsledku v databázi Scopus

2-s2.0-85075453864