Protective effect of hydroxytyrosol and its predominant plasmatic human metabolites against endothelial dysfunction in human aortic endothelial cells

Catalán Santos, Úrsula; López de las Hazas Mingo, María del Carmen; Rubió Piqué, Laura; Fernández Castillejo, Sara; Pedret, Anna; De la Torre, Rafael; Motilva Casado, Mª José; Solà, Rosa

doi:https://doi.org/10.1002/mnfr.201500361

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2015

Author

Catalán Santos, Úrsula

López de las Hazas Mingo, María del Carmen

Rubió Piqué, Laura

Fernández Castillejo, Sara

Pedret, Anna

De la Torre, Rafael

Motilva Casado, Mª José

Solà, Rosa

Suggested citation

Catalán Santos, Úrsula; López de las Hazas Mingo, María del Carmen; Rubió Piqué, Laura; Fernández Castillejo, Sara; Pedret, Anna; De la Torre, Rafael; ... Solà, Rosa. (2015) . Protective effect of hydroxytyrosol and its predominant plasmatic human metabolites against endothelial dysfunction in human aortic endothelial cells. Molecular Nutrition & Food Research, 2015, vol. 59, núm. 12, p. 2523–2536. https://doi.org/10.1002/mnfr.201500361.

Abstract

Scope Hydroxytyrosol (HT) is the major phenolic compound in virgin olive oil (VOO) in free and conjugated forms that may exert health benefits against atherosclerosis. The native form of HT is undetectable in plasma due to an extensive first pass phase II metabolism. Therefore, it is necessary to find strategies to obtain HT metabolites and to demonstrate their protective role against the endothelial dysfunction. Methods and results Biosynthesis of the main plasmatic HT metabolites was performed through Caco-2 cells. The bioactivity of HT and the mixture of metabolites was tested at physiological concentrations (1, 2, 5, and 10 μM) in human aortic endothelial cells (HAEC) co-incubated with TNF-α (10 ng/mL) for 18 and 24 h. After the incubations, cells and media were analyzed to test possible deconjugation of metabolites or conjugation of HT. Both HT and metabolites significantly reduced the secretion of E-selectin, P-selectin, ICAM-1, and VCAM-1, but only HT metabolites further reduced MCP-1 at 24 h. HT underwent a conjugation process after incubation leading to its main metabolites in a dose-dependent manner. Conclusion Physiological HT metabolites, synthetized for the first time by using an intestinal cell model, might be responsible in part for the protection against endothelial dysfunction.

URI

http://hdl.handle.net/10459.1/59520

DOI

https://doi.org/10.1002/mnfr.201500361

Is part of

Molecular Nutrition & Food Research, 2015, vol. 59, núm. 12, p. 2523–2536