title: Polyphenols of cocoa: inhibition of mammalian 15-lipoxygenase.
abstract: Some cocoas and chocolates are rich in (-)-epicatechin and its related oligomers, the procyanidins. Fractions of these compounds, isolated from the seeds of Theobroma cacao, caused dose-dependent inhibition of isolated rabbit 15-lipoxygenase-1 with the larger oligomers being more active; the decamer fraction revealed an IC50 of 0.8 microM. Among the monomeric flavanols, epigallocatechin gallate (IC50 = 4 microM) and epicatechin gallate (5 microM) were more potent than (-)-epicatechin (IC50 = 60 microM). (-)-Epicatechin and procyanidin nonamer also inhibited the formation of 15-hydroxy-eicosatetraenoic acid from arachidonic acid in rabbit smooth muscle cells transfected with human 15-lipoxygenase-1. In contrast, inhibition of the lipoxygenase pathway in J774A.1 cells transfected with porcine leukocyte-type 12-lipoxygenase (another representative of the 12/15-lipoxygenase family) was only observed upon sonication of the cells, suggesting a membrane barrier for flavanols in these cells. Moreover, epicatechin (IC50 approx. 15 microM) and the procyanidin decamer inhibited recombinant human platelet 12-lipoxygenase. These observations suggest general lipoxygenase-inhibitory potency of flavanols and procyanidins that may contribute to their putative beneficial effects on the cardiovascular system in man. Thus, they may provide a plausible explanation for recent literature reports indicating that procyanidins decrease the leukotriene/prostacyclin ratio in humans and human aortic endothelial cells.
authors.affiliation: Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Schewe
authors.forename: C
authors.initials: C
authors.lastname: Sadik
authors.forename: L O
authors.initials: LO
authors.lastname: Klotz
authors.forename: T
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: H
authors.initials: H
authors.lastname: Kühn
authors.forename: H
authors.initials: H
authors.lastname: Sies
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics; D002099:Cacao / Q000378:metabolism*; D002392:Catechin / Q000494:pharmacology; D002478:Cells, Cultured; D004537:Eicosanoic Acids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D005419:Flavonoids; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis / Q000096:biosynthesis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D008264:Macrophages / Q000201:enzymology; D051379:Mice; D010636:Phenols / Q000378:metabolism / Q000494:pharmacology*; D010936:Plant Extracts; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D012156:Reticulocytes / Q000201:enzymology; D013025:Glycine max / Q000201:enzymology; D013552:Swine; D014162:Transfection
chemical_list: D004537:Eicosanoic Acids; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006893:Hydroxyeicosatetraenoic Acids; D008077:Lipoproteins, LDL; D016859:Lipoxygenase Inhibitors; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D002392:Catechin; D001093:Arachidonate 15-Lipoxygenase; C094477:arachidic acid