title: The surge of flavonoids as novel, fine regulators of cardiovascular Cavchannels.
abstract: Ion channels underlie a wide variety of physiological processes that involve rapid changes in cell dynamics, such as cardiac and vascular smooth muscle contraction. Overexpression or dysfunction of these membrane proteins are the basis of many cardiovascular diseases that represent the leading cause of morbidity and mortality for human beings. In the last few years, flavonoids, widely distributed in the plant kingdom, have attracted the interest of many laboratories as an emerging class of fine ion, in particular Cav, channels modulators. Pieces of in vitro evidence for direct as well as indirect effects exerted by various flavonoids on ion channel currents are now accumulating in the scientific literature. This activity may be responsible, at least in part, for the beneficial and protective effects of dietary flavonoids toward cardiovascular diseases highlighted in several epidemiological studies. Here we examine numerous studies aimed at analysing this feature of flavonoids, focusing on the mechanisms that promote their sometimes controversial activities at cardiovascular Cavchannels. New methodological approaches, such as molecular modelling and docking to Cav1.2 channel α1csubunit, used to elucidate flavonoids intrinsic mechanism of action, are introduced. Moreover, flavonoid-membrane interaction, bioavailability, and antioxidant activity are taken into account and discussed.
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy. Electronic address: fabio.fusi@unisi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fusi
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy.
authors.forename: Ottavia
authors.initials: O
authors.lastname: Spiga
authors.affiliation: Dipartimento di Biotecnologie, Chimica e Farmacia, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Trezza
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Sgaragli
authors.affiliation: Dipartimento di Scienze della Vita, Università degli Studi di Siena, via A. Moro 2, 53100 Siena, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Saponara
mesh_terms: D000818:Animals; D001682:Biological Availability; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D005419:Flavonoids
keywords: (S)-(-)-Bay K 8644 (PubChem CID: 6603728); Ca(v)1.2 channel; Cardiovascular system; Daidzein (PubChem CID: 5281708); Flavonoid; Genistein (PubChem CID: 5280961); Molecular docking; Myricetin (PubChem CID: 5281672); Patch-clamp; Quercetin; Quercetin (PubChem CID: 5280343)