Flavonoids of cocoa inhibit recombinant human 5-lipoxygenase.
(-)-Epicatechin and its related oligomers, the procyanidins, are present in sizable amounts in some cocoas and chocolates. Intake of flavonoid-rich chocolate in humans has been reported to increase the plasma level of (-)-epicatechin and concomitantly to significantly decrease the plasma level of proinflammatory cysteinyl leukotrienes. Because leukotrienes are formed via the 5-lipoxygenase pathway of arachidonic acid metabolism, we examined whether 5-lipoxygenase is a possible target for the flavonoids of cocoa. Recombinant human 5-lipoxygenase was reacted with arachidonic acid and yielded a mixture of mainly 5-hydroperoxy-6E,8Z, 11Z,14Z-eicosatetraenoic acid (5-HpETE) and hydrolysis products of 5,6-leukotriene A(4) (LTA(4)). The formation of these products was significantly inhibited by (-)-epicatechin in a dose-dependent manner with 50% inhibitory concentrations (IC(50)) of 22 and 50 micromol/L, respectively. Among the procyanidin fractions isolated from the seeds of Theobroma cacao, only the dimer fraction and, to a lesser extent, the trimer through pentamer fractions exhibited comparable effects, whereas the larger procyanidins (hexamer through nonamer) were almost inactive. We conclude that (-)-epicatechin and its low-molecular procyanidins inhibit both dioxygenase and LTA(4) synthase activities of human 5-lipoxygenase and that this action may contribute to a putative anti-inflammatory effect of cocoa products.
Schewe
Tankred
T
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Kühn
Hartmut
H
Sies
Helmut
H
D000975:Antioxidants / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D044946:Biflavonoids; D002099:Cacao / Q000737:chemistry*; D002392:Catechin / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D005419:Flavonoids / Q000032:analysis* / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D017572:Leukotriene A4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D008970:Molecular Weight; D044945:Proanthocyanidins; D020033:Protein Isoforms / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D000975:Antioxidants; D044946:Biflavonoids; D005419:Flavonoids; D017572:Leukotriene A4; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D044945:Proanthocyanidins; D020033:Protein Isoforms; D011994:Recombinant Proteins; C017674:procyanidin; C025348:arachidonic acid 5-hydroperoxide; D002392:Catechin