title: (-)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase.
abstract: Dietary (-)-epicatechin is known to improve bioactivity of (*)NO in arterial endothelium of humans, but the mode of action is unclear. We used the fluorophore 4,5-diaminofluorescein diacetate to visualize the (*)NO level in living human umbilical vein endothelial cells (HUVEC). Untreated cells showed only a weak signal, whereas pretreatment with (-)-epicatechin (10 microM) or apocynin (100 microM) elevated the (*)NO level. The effects were more pronounced when the cells were treated with angiotensin II with or without preloading of the cells with (*)NO via PAPA-NONOate. While (-)-epicatechin scavenged O2(*-), its O-methylated metabolites prevented O2(*-) generation through inhibition of endothelial NADPH oxidase activity, even more strongly than apocynin. From the effect of 3,5-dinitrocatechol, an inhibitor of catechol-O-methyltransferase (COMT), on HUVEC it is concluded that (-)-epicatechin serves as 'prodrug' for conversion to apocynin-like NADPH oxidase inhibitors. These data indicate an (*)NO-preserving effect of (-)-epicatechin via suppression of O2(*-)-mediated loss of (*)NO.
authors.affiliation: Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, D-40001 Düsseldorf, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Steffen
authors.forename: Tankred
authors.initials: T
authors.lastname: Schewe
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
mesh_terms: D000098:Acetophenones / Q000737:chemistry / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D015398:Signal Transduction; D014470:Umbilical Cord / Q000187:drug effects / Q000378:metabolism
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; D002392:Catechin; C056165:acetovanillone; D019255:NADPH Oxidases; D006152:Cyclic GMP