Grape seed-derived procyanidins alleviate gout pain via NLRP3 inflammasome suppression

J Neuroinflammation. 2017 Apr 4;14(1):74. doi: 10.1186/s12974-017-0849-y.

Abstract

Background: Gout is one of the common inflammatory arthritis which affects many people for inflicting unbearable pain. Macrophage-mediated inflammation plays an important role in gout. The uptake of monosodium urate (MSU) crystals by macrophages can lead to activation of NOD-like receptors containing a PYD 3 (NLRP3) inflammasome, thus accelerating interleukin (IL)-1β production. Reactive oxygen species (ROS) promoted development of the inflammatory process through NLRP3 inflammasome. Our study aimed to find a food-derived compound to attenuate gout pain via the specific inhibition of the NLRP3 inflammasome in macrophages.

Methods: CD-1 mice were used to evaluate the degree of pain and the swelling dimension of joints after an intra-articular (IA) MSU injection in the ankle. The murine macrophage cell line Raw 264.7 was used to investigate the effects of procyanidins and the mechanism underlying such effects. Histological analysis was used to measure the infiltration of inflammatory cells. ROS produced from Raw 264.7 cells were evaluated by flow cytometry. Cell signaling was measured by Western blot assay and immunofluorescence.

Results: Procyanidins significantly attenuated gout pain and suppressed ankle swelling. Procyanidins also inhibited MSU-induced activation of the NLRP3 inflammasome and increase of IL-1β. Furthermore, procyanidins decreased ROS levels in Raw 264.7 cells.

Conclusions: Suppression of the NLRP3 inflammasome in macrophages contributes to the amelioration of gout pain by procyanidins.

Keywords: Gout pain; Macrophages; NLRP3 inflammasome; Procyanidins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankle / physiopathology
  • Anti-Inflammatory Agents / therapeutic use*
  • Antioxidants / toxicity*
  • Colchicine / analogs & derivatives
  • Colchicine / pharmacology
  • Cytokines / metabolism
  • Gout / chemically induced
  • Gout / complications
  • Grape Seed Extract / therapeutic use*
  • Inflammation / chemically induced
  • Inflammation / complications
  • Inflammation / drug therapy*
  • Lipopolysaccharides / pharmacology
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Pain / complications*
  • Pain / drug therapy
  • Pain / etiology
  • Phosphorylation / drug effects
  • Proanthocyanidins / therapeutic use*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Uric Acid / toxicity
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Grape Seed Extract
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Proanthocyanidins
  • Reactive Oxygen Species
  • Uric Acid
  • p38 Mitogen-Activated Protein Kinases
  • colchiceine
  • Colchicine