A blend of polyphenolic compounds explains the stimulatory effect of red wine on human endothelial NO synthase.
A high intake of polyphenolic compounds is likely to have beneficial effects on the cardiovascular system. Especially red wine is a rich source of polyphenols, and we have previously shown that French red wine upregulates eNOS, a protective enzyme in the cardiovascular system. The current study tested (poly)phenolic constituents of red wine for their ability to enhance eNOS expression (and the activity of a 3.5-kb human eNOS promoter) in human EA.hy 926 endothelial cells. Of the compounds tested, we found 3,4',5-trihydroxy-trans-stilbene (trans-resveratrol) to be the most efficacious stimulator of eNOS expression (and eNOS transcription), but this compound alone could not explain the total stimulatory effect of red wine. The flavanols catechin and epicatechin, the flavonols fisetin, myricetin, isoquercitrin and hyperoside, the anthocyanins delphinidin, malvidin, and paeonidin, gallic acid, and the hydroxycinnamic acids ferulic acid and sinapinic acid did not change eNOS expression or eNOS promoter activity in any substantial way. The flavonol quercetin inhibited eNOS expression (with no effect on eNOS promoter activity). Cinnamic acid was a rather potent enhancer of eNOS expression, however with an efficacy of only 170%. Surprisingly, it reduced eNOS promoter activity. The anthocyanins cyanidin, the hydroxycinnamic acids p-coumaric acid and caffeic acid, and the phenolic acids benzoic acid and vanillic acid also enhanced eNOS expression moderately (with no effect on eNOS promoter activity). Thus, the increase in eNOS in response to red wine involves several polyphenolic compounds with a major contribution from trans-resveratrol and lesser contributions from cinnamic and hydroxycinnamic acids, cyanidin, and some phenolic acids.
Wallerath
Thomas
T
Department of Pharmacology, Johannes Gutenberg University, D-55101 Mainz, Germany.
Li
Huige
H
Gödtel-Ambrust
Ute
U
Schwarz
Petra M
PM
Förstermann
Ulrich
U
D000872:Anthocyanins / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D008968:Molecular Conformation; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D014920:Wine
D000872:Anthocyanins; D002934:Cinnamates; D005419:Flavonoids; D062385:Hydroxybenzoates; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D013267:Stilbenes; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III