title: The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation- and Oxidative Stress-Induced Dysfunction ofIn VitroCultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis.
abstract: Atherosclerosis is characterized by endothelial dysfunction, mainly induced by inflammation and oxidative stress. Increased reactive oxygen species (ROS) production together with increased adhesion molecules and thrombogenic tissue factor (TF) expression on endothelial cells has a key role in proatherogenic mechanisms. Therefore downmodulation of these molecules could be useful for reducing the severity of inflammation and atherosclerosis progression. Dehydrozingerone (DHZ) is a nutraceutical compound with anti-inflammatory and antioxidant activities. In this study we evaluated the ability of DHZ and its symmetric dimer to modulate hydrogen peroxide- (H2O2-) induced ROS production in human umbilical vein endothelial cells (HUVEC). We also evaluated intercellular adhesion molecule- (ICAM-) 1, vascular cell adhesion molecule- (VCAM-) 1, and TF expression in HUVEC activated by tumor necrosis factor- (TNF-)α. HUVEC pretreatment with DHZ and DHZ dimer reduced H2O2-induced ROS production and inhibited adhesion molecule expression and secretion. Of note, only DHZ dimer was able to reduce TF expression. DHZ effects were in part mediated by the inhibition of the nuclear factor- (NF-)κB activation. Overall, our findings demonstrate that the DHZ dimer exerts a potent anti-inflammatory, antioxidant, and antithrombotic activity on endothelial cells and suggest potential usefulness of this compound to contrast the pathogenic mechanisms involved in atherosclerosis progression.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Elisabetta
authors.identifier: 0000-0002-7261-8884
authors.initials: E
authors.lastname: Profumo
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Brigitta
authors.identifier: 0000-0002-0575-4106
authors.initials: B
authors.lastname: Buttari
authors.affiliation: Laboratory of Vascular Pathology, Istituto Dermopatico Dell'Immacolata-IRCCS, Fondazione Luigi Maria Monti, Via Monti Creta 104, 00167 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Arcangelo
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Tinaburri
authors.affiliation: Istituto di Chimica Biomolecolare, CNR, Traversa La Crucca 3, 07100 Sassari, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Dettori
authors.affiliation: Istituto di Chimica Biomolecolare, CNR, Traversa La Crucca 3, 07100 Sassari, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Fabbri
authors.affiliation: Istituto di Chimica Biomolecolare, CNR, Traversa La Crucca 3, 07100 Sassari, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Delogu
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Rachele
authors.identifier: 0000-0003-3014-3523
authors.initials: R
authors.lastname: Riganò
mesh_terms: D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019587:Dietary Supplements; D019281:Dimerization; D005470:Fluorometry; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility; D013343:Styrenes / Q000494:pharmacology / Q000627:therapeutic use*; D013925:Thromboplastin / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013343:Styrenes; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C052933:methyl-3-methoxy-4-hydroxystyryl ketone; D013925:Thromboplastin