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

Úrsula Catalán, Maria Carmen López de las Hazas, Laura Rubió, Sara Fernández-Castillejo, Anna Pedret, Rafael de la Torre, Maria José Motilva, Rosa Solà

    Research output: Contribution to journalArticleResearchpeer-review

    42 Citations (Scopus)

    Abstract

    © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 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.
    Original languageEnglish
    Pages (from-to)2523-2536
    JournalMolecular Nutrition and Food Research
    Volume59
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2015

    Keywords

    • Atherosclerosis
    • Caco-2
    • Human aortic endothelial cells
    • Hydroxytyrosol
    • Hydroxytyrosol metabolites

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