Úrsula Catalán1, Maria-Carmen López de Las Hazas2, Laura Rubió1,2, Sara Fernández-Castillejo1, Anna Pedret1, Rafael de la Torre3, Maria-José Motilva2, Rosa Solà1. 1. Functional Nutrition, Oxidation and Cardiovascular Diseases Group (NFOC-Salut), Unit of Lipids and Atherosclerosis Research (URLA), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Hospital Universitari Sant Joan, IISPV, Technological Center of Nutrition and Health (CTNS), Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain. 2. Food Technology Department, Universitat de Lleida-AGROTECNIO Center, Lleida, Lleida, Spain. 3. Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Institut Hospital del Mar d'Investigacions Mediques (IMIM), Barcelona, Spain.
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.
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.
Authors: Martin Liehr; Alessandro Mereu; Jose Javier Pastor; Jose Carlos Quintela; Stefanie Staats; Gerald Rimbach; Ignacio Rodolfo Ipharraguerre Journal: PLoS One Date: 2017-03-27 Impact factor: 3.240