Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice

J Pharmacol Exp Ther. 2011 Dec;339(3):859-69. doi: 10.1124/jpet.111.182808. Epub 2011 Aug 31.


The aim of this study was to investigate the effect of oleuropein aglycone, an olive oil compound, on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). CIA was induced in mice by an intradermal injection of 100 μl of an emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice developed erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 28 in the CII-challenged mice and the severity of CIA progressed over a 35-day period with resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with oleuropein aglycone starting at the onset of arthritis (day 25) ameliorated the clinical signs at days 26 to 35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was also significantly reduced in oleuropein aglycone-treated mice. Plasma levels of the proinflammatory cytokines were also significantly reduced by oleuropein aglycone. In addition, we have confirmed the beneficial effects of oleuropein aglycone on an experimental model of CIA in a therapeutic regimen of post-treatment, with treatment started at day 28, demonstrating that oleuropein aglycone exerts an anti-inflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / biosynthesis
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Cattle
  • Collagen Type II
  • Cytokines / blood
  • Dinoprostone / blood
  • Disease Models, Animal
  • Disease Progression
  • Drug Administration Schedule
  • Drug Evaluation, Preclinical
  • Iridoids
  • Joints / drug effects
  • Joints / pathology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Nitric Oxide Synthase Type II / biosynthesis
  • Olive Oil
  • Peroxidase / metabolism
  • Plant Oils / chemistry
  • Pyrans / pharmacology
  • Pyrans / therapeutic use*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Collagen Type II
  • Cytokines
  • Iridoids
  • Olive Oil
  • Plant Oils
  • Pyrans
  • oleuropein
  • Alcohol Oxidoreductases
  • phenylacetaldehyde reductase
  • Peroxidase
  • Nitric Oxide Synthase Type II
  • Dinoprostone