Resveratrol lowers synovial hyperplasia, inflammatory markers and oxidative damage in an acute antigen-induced arthritis model

Rheumatology (Oxford). 2016 Oct;55(10):1889-900. doi: 10.1093/rheumatology/kew255. Epub 2016 Jun 28.


Objective: The present study aimed to determine the protective effects of dietary supplementation with resveratrol (RSV) in an acute antigen-induced arthritis (AIA) model.

Methods: Rats were randomly divided into three groups: control, AIA and RSV-treated AIA group. RSV (12.5 mg/kg/day) was given orally for 8 weeks before induction of AIA and until the end of the experiment (48 h after intra-articular injection). The control and AIA animals were administered 100 μl of water. Results were evaluated by macroscopic observation, histopathology and immunohistochemistry for anti-PCNA, macrophages (CD68), T lymphocytes (CD3), monocyte chemoattractant protein-1 and 8-oxo-7,8-dihydro-2'-deoxyguanine (a marker of DNA damage). Cytokine-induced neutrophil chemoattractant-1 in serum and peroxidase activity in synovial tissue were measured using commercial kits.

Results: At the end of the study, RSV significantly reduced knee swelling. Likewise, the histological score of synovial tissue also reduced significantly. The arthritis-protective effects were associated with a significant decrease in PCNA, CD68, CD3 and monocyte chemoattractant protein-1 staining, as well as a reduction in serum concentrations of cytokine-induced neutrophil chemoattractant-1. RSV treatment also decreased the level of the marker of DNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanine. Accordingly, peroxidase activity in the synovial tissue was up-regulated.

Conclusion: Dietary supplementation with RSV lowers the main pathological hallmarks of RA disease in an acute model of AIA. RSV may represent a promising strategy in controlling the severity of RA.

Keywords: antioxidant; diet; inflammation; oxidative stress; resveratrol; rheumatoid arthritis; synovial tissue hyperplasia.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Cell Proliferation / drug effects
  • Cytokines / drug effects
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Hyperplasia / immunology
  • Hyperplasia / prevention & control
  • Immunity, Cellular
  • Peroxidase / antagonists & inhibitors
  • Random Allocation
  • Rats, Inbred Lew
  • Resveratrol
  • Stilbenes / pharmacology*
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology*


  • Antioxidants
  • Cytokines
  • Stilbenes
  • Peroxidase
  • Resveratrol