Scopoletin suppresses IL-6 production from fibroblast-like synoviocytes of adjuvant arthritis rats induced by IL-1β stimulation

Int Immunopharmacol. 2013 Dec;17(4):1037-43. doi: 10.1016/j.intimp.2013.10.011.


Scopoletin, a coumarin compound naturally occurring in many medicinal plants, has previously been demonstrated to ameliorate synovial inflammation and destruction of cartilage and bone in adjuvant arthritis (AA) rats. As interleukin (IL)-6 is critically involved in the initiation and development of rheumatoid arthritis (RA), the present study was performed to investigate the effect of scopoletin on IL-6 production from fibroblast-like synoviocytes (FLS) to get insight into its anti-RA mechanisms. FLS were isolated from synovial membrane tissues of AA rats, and stimulated with IL-1β (10 ng/mL). Scopoletin, at concentrations of 15, 30, and 60 μM, was shown to only moderately inhibit FLS proliferation, but dramatically reduce IL-6 production at both mRNA and protein levels. It also inhibited the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), protein kinase C (PKC) and cAMP response element binding protein (CREB). These findings suggest that scopoletin exerts anti-RA action probably through suppressing IL-6 production from FLS via MAPK/PKC/CREB pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arthritis, Experimental / immunology*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclic AMP Response Element-Binding Protein / immunology
  • Fibroblasts / cytology
  • Interleukin-1beta
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Male
  • Mitogen-Activated Protein Kinases / immunology
  • Protein Kinase C / immunology
  • RNA, Messenger / immunology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Interleukin-1 / genetics
  • Scopoletin / pharmacology*
  • Synovial Membrane / cytology


  • Anti-Inflammatory Agents
  • Cyclic AMP Response Element-Binding Protein
  • Interleukin-1beta
  • Interleukin-6
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Scopoletin