title: Cocoa polyphenols and inflammatory mediators.
abstract: Cocoa products are sources of flavan-3-ols, which have attracted interest regarding cardiovascular health. This review provides a survey of our research on the effects of cocoa polyphenols on leukotriene and nitric oxide (NO) metabolism and on myeloperoxidase-induced modification of LDL. Because intake of flavonoid-rich chocolate by human subjects was reported to decrease the plasma concentrations of proinflammatory cysteinyl leukotrienes, we assessed whether cocoa polyphenols inhibited human 5-lipoxygenase, the key enzyme of leukotriene synthesis. (-)-Epicatechin and other cocoa flavan-3-ols proved to be inhibitory at the enzyme level. This action may confer antileukotriene action in vivo. In a double-blind crossover study, 20 individuals at risk for cardiovascular diseases received cocoa beverages with high or low contents of flavan-3-ols. NO-dependent, flow-mediated dilation of the brachial artery and concentrations of nitroso compounds in plasma were measured, and it was shown that ingestion of the high-flavanol coca drink but not the low-flavanol cocoa drink significantly increased plasma concentrations of nitroso compounds and flow-mediated dilation of the brachial artery. Therefore, ingested flavonoids may reverse endothelial dysfunction through enhancement of NO bioactivity. Oxidative modification of LDL appears to be crucial for atherogenesis, and one of the mediators is the proinflammatory proatherogenic enzyme myeloperoxidase. Micromolar concentrations of (-)-epicatechin or other flavonoids were found to suppress lipid peroxidation in LDL induced by myeloperoxidase in the presence of physiologically relevant concentrations of nitrite, an NO metabolite. Adverse effects of NO metabolites, such as nitrite and peroxynitrite, were thus attenuated.
authors.affiliation: Institute for Biochemistry and Molecular Biology I and the Department of Medicine, Division of Cardiology, Pulmonary Diseases, and Angiology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. sies@uni-duesseldorf.de
authors.forename: Helmut
authors.initials: H
authors.lastname: Sies
authors.forename: Tankred
authors.initials: T
authors.lastname: Schewe
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002099:Cacao; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008084:Lipoxygenase / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D009195:Peroxidase / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D015289:Leukotrienes; D009569:Nitric Oxide; C404987:flavan-3-ol; D009195:Peroxidase; D008084:Lipoxygenase