Hydroxytyrosol, tyrosol and their phase II metabolites as inhibitors of endothelial cell inflammation induced by high glucose levels

The aim of this investigation was to evaluate the protective effect of the main extra-virgin olive oil (EVOO) phenolic compounds, HT and Tyr, and their phase II metabolites, against the inflammatory response in HUVEC monolayers under hyperglycemic conditions. The alteration of endothelial barrier in HUVEC, treated with high glucose (HG, 30 mM) alone or together with EVOO phenols (1 μM), was evaluated through FITC-Dextran cell permeability test and the determination of TJ proteins occludin, zonulin and JAM-A level, in relation to redox-sensitive MAPK modulation, NLRP3 protein level and cytokines release. Obtained data showed that HG-induced increase of permeability through the alteration of TJ proteins, following the activation of upstream pathways involved in the inflammatory process such as p38, ERK1/2 and NLRP3, was reverted by pre-treatment with EVOO phenols and their metabolites, strengthening the hypothesis that these dietary compounds may exert a significant role in the maintenance of endothelial barrier integrity. • Hyperglycemia causes endothelial inflammation and impaired permeability. • EVOO phenols protect against hyperglycemia-induced endothelial dysfunction. • Upstream inflammatory signaling pathways were modulated by EVOO phenols. • Phase II metabolites of hydroxytyrosol and tyrosol showed comparable efficacy.