Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F15%3A33153848" target="_blank" >RIV/61989592:15310/15:33153848 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/15:10312776

Výsledek na webu

<a href="http://www.sciencedirect.com/science/article/pii/S0378427415000259" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0378427415000259</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.toxlet.2015.01.013" target="_blank" >10.1016/j.toxlet.2015.01.013</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR)

Popis výsledku v původním jazyce

The constitutive androstane receptor (CAR) is a crucial transcriptional regulator of key xenobiotic-metabolizing enzymes such as cytochrome P450 CYP3A4, CYP2C9 and CYP2B6. The flavonoids chrysin, baicalein and galangin have been reported to activate CARand interfere with EGFR signaling. Nevertheless, it is not known if these flavonoids are direct CAR ligands or indirect phenobarbital-like CAR activators via the inhibition of epidermal growth factor receptor (EGFR) signaling. We analyze the interactionsof chrysin, galangin and baicalein and its glycoside baicalin with human CAR. We have employed and validated methods that can study direct interaction with the CAR ligand binding pocket. Secondly, we determined if the compounds affect human EGFR signaling and interact with EGFR. Employing a TR-FRET coactivator assay with recombinant CAR or CAR assembly assay, a consistent activation of CAR with flavonoids and phenobarbital was not observed. It was determined, however, that galangin, chr

Název v anglickém jazyce

Chrysin, baicalein and galangin are indirect activators of the human constitutive androstane receptor (CAR)

Popis výsledku anglicky

The constitutive androstane receptor (CAR) is a crucial transcriptional regulator of key xenobiotic-metabolizing enzymes such as cytochrome P450 CYP3A4, CYP2C9 and CYP2B6. The flavonoids chrysin, baicalein and galangin have been reported to activate CARand interfere with EGFR signaling. Nevertheless, it is not known if these flavonoids are direct CAR ligands or indirect phenobarbital-like CAR activators via the inhibition of epidermal growth factor receptor (EGFR) signaling. We analyze the interactionsof chrysin, galangin and baicalein and its glycoside baicalin with human CAR. We have employed and validated methods that can study direct interaction with the CAR ligand binding pocket. Secondly, we determined if the compounds affect human EGFR signaling and interact with EGFR. Employing a TR-FRET coactivator assay with recombinant CAR or CAR assembly assay, a consistent activation of CAR with flavonoids and phenobarbital was not observed. It was determined, however, that galangin, chr

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centrum interakcí potravních doplňků s léčivy a nutrigenetiky</a><br>

Návaznosti

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

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Toxicology Letters

ISSN

0378-4274

e-ISSN

—

Svazek periodika

233

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

10

Strana od-do

68-77

Kód UT WoS článku

000349631300002

EID výsledku v databázi Scopus

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