title: 3-O-Hydroxytyrosol glucuronide and 4-O-hydroxytyrosol glucuronide reduce endoplasmic reticulum stress in vitro.
abstract: Endoplasmic reticulum (ER) stress is important for atherosclerosis development and is mediated by the unfolded protein response (UPR). In this work, we synthesized two among the most physiologically-prominent hydroxytyrosol HT hepatic metabolites, i.e. 3-O-HT glucuronide and 4-O-HT glucuronide and we tested their activities on ER stress (in human hepatocarcinoma HepG2 cells), to gain further insight into the cardiopreventive properties of HT, extra virgin olive oil, and the Mediterranean diet. We report that 3-O-HT glucuronide and 4-O-HT glucuronide inhibit tunicamycin-induced ER stress. As compared with the effects of the parent molecule, 3-O-HT glucuronide and 4-O-HT glucuronide at 10 μM and 25 μM alone induced a milder change in mRNA expression levels of both CCAAT-enhancer-binding protein homologous protein (CHOP) and glucose regulated protein GRP78 immunoglobulin heavy chain binding protein (BiP). In conclusion, we add further evidence to the hypothesis that the HT intake might be atheroprotective and reiterate the usefulness to preferably use high-quality, high-(poly)phenol extra virgin olive oil as a prominent condiment.
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA) - Food, UAM+CSIC, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Giordano
authors.forename: Olivier
authors.initials: O
authors.lastname: Dangles
authors.forename: Njara
authors.initials: N
authors.lastname: Rakotomanomana
authors.forename: Silvia
authors.initials: S
authors.lastname: Baracchini
authors.forename: Francesco
authors.initials: F
authors.lastname: Visioli
mesh_terms: D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D020719:Glucuronides / Q000737:chemistry / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D000069463:Olive Oil / Q000737:chemistry; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D056811:Unfolded Protein Response
chemical_list: C000609665:3-O-hydroxytyrosol glucuronide; C000609664:4-O-hydroxytyrosol glucuronide; D022762:CCAAT-Enhancer-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D020719:Glucuronides; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D000069463:Olive Oil; C005975:3,4-dihydroxyphenylethanol; D010626:Phenylethyl Alcohol