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Keywords:

  • Rheumatoid arthritis (RA);
  • Synovial fibroblast (SFB);
  • Luteolin;
  • Collagen-induced arthritis (CIA);
  • Proliferation

Abstract

Hyperproliferation of synovial fibroblasts is considered to be a pivotal event in the pathogenesis of rheumatoid arthritis (RA). Luteolin, a flavonoid, inhibits the proliferation of synovial fibroblasts in collagen-induced arthritic rats. Treatment with luteolin also decreases the secretion of matrix metalloprotease-1 and −3 and the expression of IL-6, IL-8, IL-15, and TGF-β. Luteolin treatment caused a delay of cells in the G2/M phase. Interestingly, combination treatment with luteolin and TNF-α exhibited a synergistic inhibitory effect in all experiments. Western blotting demonstrated that treatment with luteolin alone or combined with TNF-α inhibited the MAPK/ERKs and PI3K-Akt pathways. These results indicate that luteolin inhibits the proliferation and partially blocks the pathogenic function of synovial fibroblasts in rheumatoid arthritis.