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Biochemical and Molecular Actions of Nutrients

Flavonoids of Cocoa Inhibit Recombinant Human 5-Lipoxygenase¹

Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, D-40001 Düsseldorf, Germany and ^* Institut für Biochemie, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, D-10098 Berlin, Germany

³To whom correspondence should be addressed. E-mail: sies{at}uni-duesseldorf.de.

(-)-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 A₄ (LTA₄). The formation of these products was significantly inhibited by (-)-epicatechin in a dose-dependent manner with 50% inhibitory concentrations (IC₅₀) of 22 and 50 µmol/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 LTA₄ synthase activities of human 5-lipoxygenase and that this action may contribute to a putative anti-inflammatory effect of cocoa products.

KEY WORDS: • arachidonic acid metabolism • chocolate • inflammation • leukotrienes • procyanidins

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