(-)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase

Biochem Biophys Res Commun. 2007 Aug 3;359(3):828-33. doi: 10.1016/j.bbrc.2007.05.200. Epub 2007 Jun 6.


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.

MeSH terms

  • Acetophenones / chemistry
  • Acetophenones / pharmacology
  • Angiotensin II / pharmacology
  • Catechin / chemistry
  • Catechin / pharmacology*
  • Cells, Cultured
  • Cyclic GMP / biosynthesis
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Methylation
  • Molecular Structure
  • NADPH Oxidases / antagonists & inhibitors*
  • NADPH Oxidases / metabolism*
  • Nitric Oxide / biosynthesis*
  • Signal Transduction
  • Umbilical Cord / drug effects
  • Umbilical Cord / metabolism


  • Acetophenones
  • Enzyme Inhibitors
  • Angiotensin II
  • Nitric Oxide
  • Catechin
  • acetovanillone
  • NADPH Oxidases
  • Cyclic GMP