Scopoletin suppresses IL-6 production from fibroblast-like  synoviocytes  of adjuvant arthritis rats induced by IL-1β stimulation.
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.
Yannong
Y
Dou
Bei
B
Tong
Zhifeng
Z
Wei
Ying
Y
Li
Yufeng
Y
Xia
Yue
Y
Dai
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000276:immunology; D005347:Fibroblasts / Q000166:cytology; D053583:Interleukin-1beta; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D011493:Protein Kinase C / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000235:genetics; D012603:Scopoletin / Q000494:pharmacology*; D013583:Synovial Membrane / Q000166:cytology; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D017362:Cyclic AMP Response Element-Binding Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases; D011493:Protein Kinase C; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D012603:Scopoletin; D000093242:Interleukin-6 Inhibitors