LAUSR

Abstract The effects of chemically synthesized metabolites (sulfate and glucuronate forms) from hydroxytyrosol (HTyr) on oxidative stress and inflammation were investigated in TNF-α-activated human endothelial cells. HTyr sulfate metabolites decreased reactive oxygen species and prevented the decrease in glutathione, glutathione peroxidase 1, and glutamate-cysteine ligase catalytic subunit and up-regulated heme oxygenase-1 levels. HTyr and all tested HTyr metabolites (HTyr sulfate > HTyr glucuronate > HTyr) suppressed the phosphorylation of nuclear factor kappa B proteins, the gene expression of intercellular and vascular adhesion molecules, E-selectin, chemokine (C C) motif ligand 2, and prostaglandin-endoperoxidase synthase 2 and the adhesion of human monocytes. In addition, HTyr sulfate metabolites suppressed plantar and ear swelling and myeloperoxidase activity in inflamed ear tissue in mice treated with carrageenan or 12-O-tetradecanoylphorbol-13-acetate. This study demonstrates the antioxidant and/or anti-inflammatory properties of HTyr metabolites in TNF-α-activated hECs and in the prevention of acute and chronic inflammation in mice.