Mono-O-methylated flavanols and other flavonoids as inhibitors of endothelial NADPH oxidase
Section snippets
Enzymes and substrates
Catechol-O-methyltransferase (COMT), S-adenosyl-l-methionine (SAM), uridine 5′-diphosphoglucuronic acid (UDP-GA) and recombinant human UDP-glucuronyl transferases (UGT) 1A7 and 1A10 were obtained from Sigma–Aldrich (St. Louis, MO), and human leukocyte myeloperoxidase and human liver microsomes from Calbiochem (Schwalbach, Germany).
Chemicals
Flavonoids and other phenolics were obtained from following sources: Isorhamnetin, procyanidin B2, propylgallate and vanilline from Fluka (Deisenhofen, Germany),
HUVEC convert (−)-epicatechin to monomethyl ethers via catechol-O-methyltransferase
Incubation of HUVEC with (−)-epicatechin for 24 h led to conversion of this flavanol to a metabolite fraction, which co-migrated with authentic 3′-O-methyl epicatechin in thin-layer chromatography (Fig. 1). Presence of 3,5-dinitrocatechol (DNC), an inhibitor of catechol-O-methyltransferase (COMT) [20], prevented this conversion. In subsequent experiments applying HPLC, the methylated metabolite fraction was identified as a mixture of 3′- and 4′-O-methyl epicatechin (Steffen et al., unpublished
Endothelial NADPH oxidase activity as a possible target of dietary polyphenols or their metabolites
In this study we provide evidence that a large variety of flavonoids and their metabolites are capable of protecting vascular endothelial cells against O2− through inhibition of endothelial NADPH oxidase activity. For methodological reason, this action was directly demonstrated using cell lysates, in which the artificial activator SDS was employed to stimulate the NADPH oxidase [17], [18]. We adduce evidence, however, that inhibition of NADPH oxidase by these polyphenols also occurs in intact
Acknowledgment
H.S. is a Fellow of the National Foundation for Cancer Research (NFCR), Bethesda, MD.
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