Hydroxytyrosol prevents hepatic endoplasmic reticulum stress in physiological concentrations

Olive oil is the essential component of the Mediterranean diet, which is associated with a lower incidence of chronic diseases and higher life expectancy. Hydroxytyrosol (HT) is a phenolic compound peculiar to olives and, hence, to virgin olive oil. Among the numerous health‐promoting properties of HT, recent findings demonstrated its ability to prevent LDL oxidation which may, ultimately, decrease cardiovascular risk. One rising risk factor for cardiovascular disease is endoplasmic reticulum (ER) stress. The roles played by the ER in cardiometabolism are likely to be relevant and manifold; mounting evidence indicates the ER as an important target of dietary or pharmacological intervention. We report the preventive activities of HT physiological concentrations toward ER stress in hepatocytes, as shown by real time‐RT PCR and Western Blot analysis of CHOP and BiP, two main components of the unfolded protein response (UPR), which is activated upon the accumulation of misfolded proteins in the ER. The protective activities of HT were superior to those of two isoflavones mostly found in soy, i.e. genistein and daidzein and of two thiolic antioxidants, i.e. lipoic acid and glutathione. Although in vivo confirmation is required, these data add mechanistic insights on specific olive phenols, such as HT, as cardioprotective compounds. Research support: Ministerio C+I España/Marie Curie Amarout EU Programme