title: 2,3-cis-procyanidins elicit endothelium-dependent relaxation in porcine coronary arteries via activation of the PI3/Akt kinase signaling pathway.
abstract: Polyphenols including procyanidins have been reported to reduce the risk of cardiovascular diseases. However, polyphenolic extracts represent complex mixtures, and detailed information on their chemical composition is commonly lacking. The aim of this study was to investigate the potential of a highly purified and chemically defined 2,3-cis-procyanidin sample (di- to hexameric [4β,8]-linked oligomers) from Nelia meyeri to relax coronary arteries and to get insight into the underlying mechanisms. The procyanidins produced a concentration-dependent relaxation in endothelium-intact vascular rings by activation of the NO and endothelium-derived hyperpolarizing factor (EDHF)-signaling pathway via PI3/Akt kinase in a redox-sensitive manner, with O2(-) as key species predominantly produced by xanthine oxidase and NADPH oxidase. Our observations in tissue bath studies were confirmed by Western blotting; 2,3-cis-procyanidins induced phosphorylation of eNOS and Akt in a ROS-dependent manner. These findings provide a basis for comparing the relaxant response and mode of action with that of structurally related proanthocyanidins. Our results may contribute to a better understanding of the potential link between the beneficial effects of proanthocyanidins on vascular health and their broad distribution in many fruits, natural food sources, and foodstuffs.
authors.affiliation: Institute of Pharmacy, Pharmaceutical Biology, Freie Universität Berlin , Königin-Luise-Strasse 2, 14195 Berlin, Germany.
authors.forename: Aurica M
authors.initials: AM
authors.lastname: Kaufeld
authors.forename: Heinz H
authors.initials: HH
authors.lastname: Pertz
authors.forename: Herbert
authors.initials: H
authors.lastname: Kolodziej
mesh_terms: D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology*; D001685:Biological Factors / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D059808:Polyphenols / Q000494:pharmacology; D044945:Proanthocyanidins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine
chemical_list: D044946:Biflavonoids; D001685:Biological Factors; D059808:Polyphenols; D044945:Proanthocyanidins; D017382:Reactive Oxygen Species; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; C017674:procyanidin; D002392:Catechin; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt