Polyphenols of cocoa: inhibition of mammalian 15-lipoxygenase.
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.
Schewe
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Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Sadik
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Klotz
L O
LO
Yoshimoto
T
T
Kühn
H
H
Sies
H
H
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
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