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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

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

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/NU21-02-00135" target="_blank" >NU21-02-00135: Cardiovascular effects of flavonoid metabolites and the impact of metabolic risk factors</a><br>

Continuities

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

Publication year

2024

Confidentiality

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

Name of the periodical

Food and Function

ISSN

2042-6496

e-ISSN

2042-650X

Volume of the periodical

15

Issue of the periodical within the volume

22

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

11047-11059

UT code for WoS article

001338990200001

EID of the result in the Scopus database

2-s2.0-85206907903