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-eicosan oid and antioxidant effects in leukocytes of the principal phenolic compoun ds from the 'polar fraction': oleuropein, tyrosol, hydroxytyrosol, and caff eic acid. In intact rat peritoneal leukocytes stimulated with calcium ionop hore, all four phenolics inhibited leukotriene B-4 generation at the 5-lipo xygenase level with effectiveness hydroxytyrosol > oleuropein > caffeic aci d > tyrosol (approximate Ec(50) values: 15, 80, 200, and 500 mu M, respecti vely). In contrast, none of these compounds caused substantial inhibition o f thromboxane generation via the cyclo oxygenase pathway. Hydroxytyrosol, c affeic acid, oleuropein, and tyrosol (decreasing order of effectiveness) al so quenched the chemiluminescence signal due to reactive oxygen species gen erated by phorbol myristate acetate-stimulated rat leukocytes. None of thes e compounds were toxic to leukocytes at the concentrations tested. We concl ude that the phenolics found in virgin olive oil possess an array of potent ially beneficial lipoxygenase-inhibitory, prostaglandin-sparing, and antiox idant properties. (C) 1999 Elsevier Science Inc.