The quercetin metabolite 4-methylcatechol causes vasodilation via voltage-gated potassium (KV) channels

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F24%3A10487253" target="_blank" >RIV/00216208:11160/24:10487253 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vV3mg0OBl5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=vV3mg0OBl5</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d3fo04672a" target="_blank" >10.1039/d3fo04672a</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The quercetin metabolite 4-methylcatechol causes vasodilation via voltage-gated potassium (KV) channels

Popis výsledku v původním jazyce

Dietary polyphenols have been associated with many beneficial cardiovascular effects. However, these effects are rather attributed to small phenolic metabolites formed by the gut microbiota, which reach sufficient concentrations in systemic circulation. 4-Methylcatechol (4-MC) is one such metabolite. As it is shown to possess considerable vasorelaxant effects, this study aimed to unravel its mechanism of action. To this end, experimental in vitro and in silico approaches were employed. In the first step, isometric tension recordings were performed on rat aortic rings. 4-MC potentiated the effect of cyclic nucleotides, but the effect was not mediated by either soluble guanylyl cyclase (sGC), modification of cyclic adenosine monophosphate levels, or protein kinase G. Hence, downstream targets such as calcium or potassium channels were considered. Inhibition of voltage-gated K+ channels (K(V)) markedly decreased the effect of 4-MC, and vasodilation was partly decreased by inhibition of the K(V)7 isoform. Contrarily, other types of K+ channels or L-type Ca2+ channels were not involved. In silico reverse docking confirmed that 4-MC binds to K(V)7.4 through hydrogen bonding and hydrophobic interactions. In particular, it interacts with two crucial residues for K(V)7.4 activation: Trp242 and Phe246. In summary, our findings suggested that 4-MC exerts vasorelaxation by opening K-V channels with the involvement of K(V)7.4.

Název v anglickém jazyce

The quercetin metabolite 4-methylcatechol causes vasodilation via voltage-gated potassium (KV) channels

Popis výsledku anglicky

Dietary polyphenols have been associated with many beneficial cardiovascular effects. However, these effects are rather attributed to small phenolic metabolites formed by the gut microbiota, which reach sufficient concentrations in systemic circulation. 4-Methylcatechol (4-MC) is one such metabolite. As it is shown to possess considerable vasorelaxant effects, this study aimed to unravel its mechanism of action. To this end, experimental in vitro and in silico approaches were employed. In the first step, isometric tension recordings were performed on rat aortic rings. 4-MC potentiated the effect of cyclic nucleotides, but the effect was not mediated by either soluble guanylyl cyclase (sGC), modification of cyclic adenosine monophosphate levels, or protein kinase G. Hence, downstream targets such as calcium or potassium channels were considered. Inhibition of voltage-gated K+ channels (K(V)) markedly decreased the effect of 4-MC, and vasodilation was partly decreased by inhibition of the K(V)7 isoform. Contrarily, other types of K+ channels or L-type Ca2+ channels were not involved. In silico reverse docking confirmed that 4-MC binds to K(V)7.4 through hydrogen bonding and hydrophobic interactions. In particular, it interacts with two crucial residues for K(V)7.4 activation: Trp242 and Phe246. In summary, our findings suggested that 4-MC exerts vasorelaxation by opening K-V channels with the involvement of K(V)7.4.

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/NU21-02-00135" target="_blank" >NU21-02-00135: Kardiovaskulární účinky flavonoidních metabolitů a vliv metabolických rizikových faktorů</a><br>

Návaznosti

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

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Food and Function

ISSN

2042-6496

e-ISSN

2042-650X

Svazek periodika

15

Číslo periodika v rámci svazku

22

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

11047-11059

Kód UT WoS článku

001338990200001

EID výsledku v databázi Scopus

2-s2.0-85206907903