Cyanidin-3-glucoside inhibits inflammatory activities in human fibroblast-like synoviocytes and in mice with collagen-induced arthritis

Clin Exp Pharmacol Physiol. 2018 Oct;45(10):1038-1045. doi: 10.1111/1440-1681.12970. Epub 2018 Jun 21.


Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint tissue inflammation. Cyanidin-3-glucoside (C3G) is a major component in the flavonoid family and has shown anti-inflammatory, anti-oxidant and anti-tumour activity. In this study, we investigated the effects of C3G on lipopolysaccharides (LPS)-induced inflammation on human rheumatoid fibroblast-like synoviocytes (FLS) and on collagen-induced arthritis (CIA) mice model. We treated FLS with C3G followed by LPS induction, the expressions of tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β) and IL-6 and the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathway were analyzed. CIA was induced in mice and the arthritic mice were treated with C3G for 3 weeks. The disease severity was compared between control and C3G treated mice. The serum levels of TNF-α, IL-1β and IL-6 were analyzed by ELISA. C3G inhibited LPS-induced TNF-α, IL-1β and IL-6 expression in FLS. Moreover, C3G inhibited LPS-induced p65 production and IκBa, p38, ERK and JNK phosphorylation. Administration of C3G significantly attenuated disease in mice with CIA and decreased the serum level of TNF-α, IL-1β and IL-6. C3G inhibited LPS-induced inflammation in human FLS by inhibiting activation of NF-κB and MAPK signalling pathway. C3G exhibited therapeutic effects in mice with CIA.

Keywords: cyanidin-3-glucoside; fibroblast-like synoviocytes; inflammation; lipopolysaccharides; rheumatoid arthritis.

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Anthocyanins / therapeutic use
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology*
  • Cell Survival / drug effects
  • Collagen / adverse effects*
  • Cytokines / biosynthesis
  • Enzyme Activation / drug effects
  • Fibroblasts / pathology*
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use
  • Humans
  • Inflammation / drug therapy
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Synoviocytes / drug effects*
  • Synoviocytes / metabolism
  • Synoviocytes / pathology*


  • Anthocyanins
  • Cytokines
  • Glucosides
  • NF-kappa B
  • cyanidin-3-O-beta-glucopyranoside
  • Collagen
  • Mitogen-Activated Protein Kinases