title: Preventive effects of dietary hydroxytyrosol acetate, an extra virgin olive oil polyphenol in murine collagen-induced arthritis.
abstract: METHODS
  Hydroxytyrosol acetate (HTy-Ac), an extra virgin olive oil (EVOO) polyphenol, has recently been reported to exhibit antioxidant and anti-inflammatory effects on LPS-stimulated macrophagesand ulcerative colitis. This study was designed to evaluate dietary HTy-Ac supplementation effects on collagen-induced arthritis (CIA) in mice.
  
  
  RESULTS
  DBA-1/J mice were fed from weaning with 0.05% HTy-Ac. After 6 weeks, arthritis was induced by type II collagen. Mice were sacrificed 42 days after first immunization. Blood was recollected and paws were histological and biochemically processed. HTy-Ac diet significantly prevent edarthritis development and decreased serum IgG1 and IgG2a, cartilage olimeric matrix protein (COMP) and metalloproteinase-3 (MMP-3) levels, as well as, pro-inflammatory cytokines levels (TNF-α, IFN-γ, IL-1β, IL-6 and IL-17A). The activation of Janus kinase-signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-kappa B (NF-κB) pathways were drastically ameliorated whereas nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein expressions were significantly up-regulated in those mice fed with HTy-Ac.
  
  
  CONCLUSIONS
  HTy-Ac improved the oxidative events and returned pro-inflammatory proteins expression to basal levels probably through JAK/STAT, MAPKs and NF-κB pathways. HTy-Ac supplement might provide a basis for developing a new dietary strategy for the prevention of rheumatoid arthritis.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain.
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Rosillo
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Sánchez-Hidalgo
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: González-Benjumea
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Spain.
authors.forename: José G
authors.initials: JG
authors.lastname: Fernández-Bolaños
authors.affiliation: Department of Rheumatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain.
authors.forename: Catalina
authors.initials: C
authors.lastname: Alarcón-de-la-Lastra
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D001323:Autoantibodies / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein / Q000097:blood; D002396:Catechols / Q000494:pharmacology*; D003094:Collagen / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008811:Mice, Inbred DBA; D000069463:Olive Oil / Q000494:pharmacology*; D000071876:Prostaglandin-E Synthases / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D000085:Acetates; D001323:Autoantibodies; D064236:Cartilage Oligomeric Matrix Protein; D002396:Catechols; D016207:Cytokines; D000069463:Olive Oil; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C524604:hydroxytyrosyl acetate; D003094:Collagen; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse
keywords: CIA; EVOO; Hydroxytyrosol acetate; Inflammation; Rheumatoid arthritis