Autophagy Activation by Resveratrol Reduces Severity of Experimental Rheumatoid Arthritis

Mol Nutr Food Res. 2021 Jan;65(2):e2000377. doi: 10.1002/mnfr.202000377. Epub 2020 Dec 7.


Scope: Previous work reported that dietary supplementation with resveratrol lowers synovial hyperplasia, inflammatory and oxidative damage in an antigen-induced arthritis (AIA) model. Here, it is investigated whether resveratrol can regulate the abnormal synovial proliferation by inducing autophagy and controlling the associated inflammatory response.

Methods and results: Animals treated with resveratrol 8 weeks before AIA induction show the highest significant signal for microtubule-associated protein 1 light chain 3 by confocal microscopy. Besides, resveratrol significantly reduces p62 expression, but it does not increase the signal of beclin-1. Also, active caspase-3 expression, as well as poly(ADP-ribose) polymerase, is upregulated in the AIA group, and is significantly reduced in resveratrol-treated AIA group. Resveratrol also mitigates angiopoietin-1 and vascular endothelial growth factor signals. Finally, resveratrol significantly reduces the serum levels of IL-1β, C reactive protein, and prostaglandin E2, as well as nuclear factor κB synovial tissue expression, which shows a significant correlation with p62 expression.

Conclusion: Dietary supplementation with resveratrol induces the noncanonical autophagy pathway and limits the cross-talk with inflammation, which in consequence modulates the synovial hyperplasia. Preventive strategies that incorporate dietary intervention with resveratrol may offer a potential therapeutic alternative to drugs to influence the risk of rheumatoid arthritis and influence its course.

Keywords: autophagy; diet; inflammation; resveratrol; rheumatoid arthritis; synovial tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / diet therapy*
  • Arthritis, Rheumatoid / etiology*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / prevention & control
  • Autophagy / drug effects*
  • Autophagy / physiology
  • C-Reactive Protein / analysis
  • Dietary Supplements
  • Dinoprostone / blood
  • Disease Models, Animal
  • Female
  • Rats
  • Rats, Inbred Lew
  • Resveratrol / pharmacology*
  • Synovial Fluid / drug effects
  • Synovial Fluid / metabolism
  • Synovial Membrane / blood supply
  • Synovial Membrane / drug effects
  • Synovial Membrane / metabolism
  • Transcription Factor RelA / metabolism


  • Transcription Factor RelA
  • C-Reactive Protein
  • Dinoprostone
  • Resveratrol