Effect of metabolites of hydroxytyrosol on protection against oxidative stress and inflammation in human endothelial cells

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 (CC) 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.Junta de Andalucía 09-CVI-5007Ministerio de Ciencia e Innovación ES-2012-056104Ministerio de Economía y Competitividad JCI-2012-1308