Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis

J Nutr Biochem. 2015 Apr;26(4):360-8. doi: 10.1016/j.jnutbio.2014.11.011. Epub 2014 Dec 30.


Virgin olive oil is the primary source of fat in the Mediterranean diet, and its beneficial health effects have been related with oleic acid and phenolic compounds content. Hydroxytyrosol, a typical virgin olive oil phenolic compound, has beneficial antioxidant and anti-inflammatory properties as previously reported. The aim of this study was to evaluate the effect of hydroxytyrosol-supplemented refined olive oil at 0.5 and 5 mg/kg in a rodent model of rheumatoid arthritis. Rheumatoid arthritis was induced by intradermic administration, in male Wistar rats, of Freund's adjuvant with collagen type II on days 1 and 21. Hydroxytyrosol-supplemented refined olive oils were administrated by gavage from day 23 until day 35. The treatment at 5-mg/kg dose significantly decreased paw edema (P<.01), histological damage, cyclooxygenase-2 and inducible nitric oxide synthase expression, and markedly reduced the degree of bone resorption, soft tissue swelling and osteophyte formation, improving articular function in treated animals. Acute inflammation, induced by carrageenan, was also evaluated for hydroxytyrosol-supplemented refined olive oils at 0.5 and 5 mg/kg. Both doses significantly reduced paw edema (P<.001). Our results suggest that the supplementation of refined olive oil with hydroxytyrosol may be advantageous in rheumatoid arthritis with significant impact not only on chronic inflammation but also on acute inflammatory processes.

Keywords: Hydroxytyrosol; Inflammation; Olive oil; Phenolic compounds; Rheumatoid arthritis.

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Arthritis, Rheumatoid / drug therapy*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dietary Supplements*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Inflammation / drug therapy*
  • Male
  • Neutrophils / cytology
  • Neutrophils / drug effects
  • Neutrophils / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Olive Oil / pharmacology*
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / blood


  • Anti-Inflammatory Agents
  • Antioxidants
  • Olive Oil
  • Tumor Necrosis Factor-alpha
  • 3,4-dihydroxyphenylethanol
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Phenylethyl Alcohol