Issue 22, 2024

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

Abstract

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 (KV) markedly decreased the effect of 4-MC, and vasodilation was partly decreased by inhibition of the KV7 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 KV7.4 through hydrogen bonding and hydrophobic interactions. In particular, it interacts with two crucial residues for KV7.4 activation: Trp242 and Phe246. In summary, our findings suggested that 4-MC exerts vasorelaxation by opening KV channels with the involvement of KV7.4.

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

Supplementary files

Article information

Article type
Paper
Submitted
27 Oct 2023
Accepted
24 Sep 2024
First published
03 Oct 2024
This article is Open Access
Creative Commons BY license

Food Funct., 2024,15, 11047-11059

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

P. Dias, R. Salam, J. Pourová, M. Vopršalová, L. Konečný, E. Jirkovský, J. Duintjer Tebbens and P. Mladěnka, Food Funct., 2024, 15, 11047 DOI: 10.1039/D3FO04672A

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