Grasas y Aceites, Vol 67, No 4 (2016)

Extra-virgin olive oil and its phenolic extract prevent inflammatory response and joint damage in murine experimental arthritis

M. A. Rosillo
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain

M. Sánchez-Hidalgo
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain

C. Alarcón-de-la-Lastra
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Spain


The consumption of EVOO in Mediterranean countries has shown beneficial effects. A wide range of evidence indicates that the phenolic compounds present in EVOO are endowed with anti-inflammatory properties. In this work, we evaluated the effects of dietary EVOO and treatment with its phenolic extract (PE) in a model of RA, the collagen-induced arthritis (CIA) in mice. On day 0, DBA-1/J mice were immunized with bovine collagen type II (CII). On day 21, the mice received a booster injection. We have demonstrated that EVOO and its PE decreases joint edema, cell migration, cartilage degradation and bone erosion. Our data indicate that dietary EVOO and PE treatment inhibit JNK, p38 and signal transducer and STAT-3. In addition, both EVOO and PE decrease NF-κB translocation leading to the down-regulation of the arthritic process. These results support the interest of natural diet components in the development of therapeutic products for arthritic conditions.


CIA; EVOO; Inflammatory response; Olive oil; Polyphenols; Rheumatoid arthritis

Full Text:



Aaronson DS, Horvath CM. 2002. A road map for those who don't know JAK-STAT. Science 296, 1653–1655.

Alarcón de la Lastra C, Barranco MD, Motilva V, Herrerias JM. 2001. Mediterranean diet and health: biological importance of olive oil. Curr Pharm Des. 7, 933–950. PMid:11472248

Bermúdez B, López S, Ortega A, Varela LM, Pacheco YM, Abia R, Muriana FJ. 2011. Oleic acid in olive oil: from a metabolic framework toward a clinical perspective. Curr. Pharm. Des. 17, 831–843. PMid:21443481

Cárdeno A, Sánchez-Hidalgo M, Alarcón-de-la-Lastra C. 2013. An up-date of olive oil phenols in inflammation and cancer: molecular mechanisms and clinical implications. Curr. Med. Chem. 20, 4758–4776. PMid:23834184

Carrillo C, Cavia M, Alonso-Torre S. 2012. Role of oleic acid in immune system; mechanism of action; a review. Nutr Hosp. 27, 978–990. PMid:23165533

Gong D, Geng C, Jiang L, Cao J, Yoshimura H, Zhong L. 2009. Effects of hydroxytyrosol-20 on carrageenan-induced acute inflammation and hyperalgesia in rats. Phytother Res. 23, 646–650. PMid:19067390

Han Z, Boyle DL, Chang L, Bennett B, Karin M, Yang L, Manning AM, Firestein GS. 2001. c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritis. J. Clin. Invest. 108, 73–81. PMid:11435459 PMCid:PMC209341

Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Morittu VM, Procopio A, Britti D, Cuzzocrea S. 2011. Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice. J. Pharmacol. Exp. Ther. 339, 859–869. PMid:21880869

Jeong JG, Kim JM, Cho H, Hahn W, Yu SS, Kim S. 2004. Effects of IL-1beta on gene expression in human rheumatoid synovial fibroblasts. Biochem. Biophys. Res. Commun. 324, 3–7. PMid:15464974

Martínez-Domínguez E, de la Puerta R, Ruiz-Gutiérrez V. 2001. Protective effects upon experimental inflammation models of a polyphenol-supplemented virgin olive oil diet. Inflamm. Res. 50, 102–106. PMid:11289653

Morel J, Berenbaum F. 2004. Signal transduction pathways: new targets for treating rheumatoid arthritis. Joint Bone Spine 71, 503–510. PMid:15589430

Okamoto H, Yoshio T, Kaneko H, Yamanaka H. 2010. Inhibition of NF-kappaB signaling by fasudil as a potential therapeutic strategy for rheumatoid arthritis. Arthritis Rheum. 62, 82–92. PMid:20039418

Omar SH. 2010. Oleuropein in olive and its pharmacological effects. Sci. Pharm. 78, 133–154. PMid:21179340 PMCid:PMC3002804

Puertollano MA, Puertollano E, Álvarez de Cienfuegos G, de Pablo Martínez MA. 2010. Olive oil, immune system and infection. Nutr. Hosp. 25, 1–8. PMid:20204249

Rudan I, Sidhu S, Papana A, Meng SJ, Xin-Wei Y, Wang W, Campbell-Page RM, Demaio AR, Nair H, Sridhar D, Theodoratou E, Dowman B, Adeloye D, Majeed A, Car J, Campbell H, Wang W, Chan KY. 2015. Prevalence of rheumatoid arthritis in low- and middle-income countries: A systematic review and analysis. J. Glob. Health 5, 010409. PMid:25969732 PMCid:PMC4416333

Salgado E, Maneiro JR. 2014. New therapies for rheumatoid arthritis. Med. Clin. (Barc) 143, 461–466. PMid:24461738

Smedslund G, Byfuglien MG, Olsen SU, Hagen KB. 2010. Effectiveness and safety of dietary interventions for rheumatoid arthritis: a systematic review of randomized controlled trials. J. Am. Diet Assoc. 110, 727–735. PMid:20430134

Suzuki M, Tetsuka T, Yoshida S, Watanabe N, Kobayashi M, Matsui N, Okamoto T. 2000. The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts. FEBS Lett. 465, 23–27.

Vázquez-Roncero A, Janer del Valle M, Janer del Valle L. 1976. Determinación de los polifenoles totales del aceite de oliva. Grasas Aceites 24, 350–357.

Copyright (c) 2016 Consejo Superior de Investigaciones Científicas (CSIC)

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Contact us

Technical support