Inhibition of leukocyte 5-lipoxygenase by phenolics from virgin olive oil

Interest in the health-promoting effects of virgin olive oil, an important part of the 'Mediterranean diet', prompted us to determine the anti-eicosanoid and antioxidant effects in leukocytes of the principal phenolic compounds from the 'polar fraction': oleuropein, tyrosol, hydroxytyrosol, and caffeic acid. In intact rat peritoneal leukocytes stimulated with calcium ionophore, all four phenolics inhibited leukotriene B4 generation at the 5-lipoxygenase level with effectiveness hydroxytyrosol > oleuropein > caffeic acid > tyrosol (approximate EC50 values: 15, 80, 200, and 500 microM, respectively). In contrast, none of these compounds caused substantial inhibition of thromboxane generation via the cyclo-oxygenase pathway. Hydroxytyrosol, caffeic acid, oleuropein, and tyrosol (decreasing order of effectiveness) also quenched the chemiluminescence signal due to reactive oxygen species generated by phorbol myristate acetate-stimulated rat leukocytes. None of these compounds were toxic to leukocytes at the concentrations tested. We conclude that the phenolics found in virgin olive oil possess an array of potentially beneficial lipoxygenase-inhibitory, prostaglandin-sparing, and antioxidant properties.