Tyrosol and its metabolites as antioxidative and anti-inflammatory molecules in human endothelial cells
2017
García Muriana, Francisco José | Montserrat de la Paz, Sergio | Lucas Rodríguez, Ricardo | Bermúdez Pulgarín, Beatriz | Jaramillo Carmona, Sara | Morales, Juan C. | Abia González, María del Rocío | López Martín, Sergio | Universidad de Sevilla. Departamento de Biología Celular | Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular e Inmunología
Tyrosol (Tyr) is a phenolic compound found in virgin olive oil. After ingestion, Tyr undergoes extensive first pass intestinal/hepatic metabolism. However, knowledge about the biological effects of Tyr metabolites is scarce. We chemically synthesized Tyr glucuronate (Tyr-GLU) and sulphate (Tyr-SUL) metabolites and explored their properties against oxidative stress and inflammation in TNF-α-treated human umbilical vein endothelial cells (hECs). Tyr and Tyr-SUL prevented the rise of reactive oxygen species, the depletion of glutathione, and the down-regulation of glutathione peroxidase 1, glutamate-cysteine ligase catalytic subunit, and heme oxygenase-1 genes. Tyr-SUL and to a lower extent Tyr and Tyr-GLU prevented the phosphorylation of NF-κB signaling proteins. Tyr-GLU and Tyr-SUL also prevented the over-expression of adhesion molecules at gene, protein, and secretory levels, and the adhesion (Tyr-SUL > Tyr-GLU) of human monocytes to hECs. In vivo, Tyr, and most notably Tyr-SUL in a dose-dependent manner, ameliorated plantar and ear edemas in mice models of acute and chronic inflammation. This study demonstrates the antioxidant and/or anti-inflammatory properties of Tyr metabolites, with Tyr-SUL being the most effective.
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显示更多 [+] 显示较少 [-]Ministerio de Economía y Competitividad JCI-2012-13084
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