Flavonoids and hERG channels: Friends or foes?
Eur J Pharmacol
; 899: 174030, 2021 May 15.
Article
em En
| MEDLINE
| ID: mdl-33727059
ABSTRACT
The cardiac action potential is regulated by several ion channels. Drugs capable to block these channels, in particular the human ether-à-go-go-related gene (hERG) channel, also known as KV11.1 channel, may lead to a potentially lethal ventricular tachyarrhythmia called "Torsades de Pointes". Thus, evaluation of the hERG channel off-target activity of novel chemical entities is nowadays required to safeguard patients as well as to avoid attrition in drug development. Flavonoids, a large class of natural compounds abundantly present in food, beverages, herbal medicines, and dietary food supplements, generally escape this assessment, though consumed in consistent amounts. Continuously growing evidence indicates that these compounds may interact with the hERG channel and block it. The present review, by examining numerous studies, summarizes the state-of-the-art in this field, describing the most significant examples of direct and indirect inhibition of the hERG channel current operated by flavonoids. A description of the molecular interactions between a few of these natural molecules and the Rattus norvegicus channel protein, achieved by an in silico approach, is also presented.
Palavras-chave
(±)-Naringenin (PubChem CID: 932); (±)-Taxifolin (PubChem CID: 439533); 7,8-Dimethoxyflavone (PubChem CID:689014); Acacetin (PubChem CID: 5280442); Apigenin (PubChem CID: 5280443); Apigenin trimethyl-ether (PubChem CID: 79730); Baicalein (PubChem CID: 5281605); Daidzein (PubChem CID: 5281708); Docking simulation; Epigallocatechin gallate (PubChem CID: 65064); Fisetin (PubChem CID: 5281614); Flavonoid; Galangin (PubChem CID: 5281616); Genistein (PubChem CID: 5280961); Hesperetin (PubChem CID: 72281); Isorhamnetin (PubChem CID: 5281654); Kaempferol (PubChem CID: 5280863); Liquiritigenin (PubChem CID: 114829); Long QT syndrome; Luteolin (PubChem CID: 5280445); Morin (PubChem CID 5281670); Myricetin (PubChem CID: 5281672); Naringin (PubChem CID: 442428); Patch-clamp; Quercetin (PubChem CID: 5280343); Rutin (PubChem CID: 5280805); Silybinin (PubChem CID: 31553); Torsades de pointes; hERG channel
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
/
Síndrome do QT Longo
/
Torsades de Pointes
/
Bloqueadores dos Canais de Potássio
/
Miócitos Cardíacos
/
Canal de Potássio ERG1
/
Frequência Cardíaca
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália