title: Paeoniflorin suppresses inflammatory mediator production and regulates G protein-coupled signaling in fibroblast-like synoviocytes of collagen induced arthritic rats.
abstract: OBJECTIVE
  To investigate the effects of Paeoniflorin (Pae) on inflammatory mediators and G protein-coupled signaling in fibroblast-like synoviocytes (FLS) from collagen induced arthritic (CIA) rats.
  
  
  METHODS
  SD rats were injected with type II collagen. Pae (25, 50, 100 mg. kg(-1)) was administered to CIA rats. The inflammation of CIA rats was evaluated by paw swelling, arthritis index and histopathology of joints. FLS were isolated and cultured. Interleukin (IL)-1 activity was measured by the 3H-TdR-intake method Tumor necrosis factor alpha (TNF-alpha), prostaglandin E2 (PGE2) and cAMP were measured by radioimmunoassay. Protein kinase A (PKA) was assessed by luminescent kinase assay. Gi was detected by Western blot.
  
  
  RESULTS
  Inflammation in CIA rats was accompanied by hyperplastic synovium, pannus and cartilage erosion in joints. IL-1 activity and Gi expression increased, PGE2 and TNF-alpha production were enhanced, but cAMP level and PKA activity decreased. Pae significantly suppressed the inflammatory response and inflammatory mediators (IL-1, TNF-alpha and PGE2) in vivo. Pae inhibited Gi expression and restored cAMP level and PKA activity in FLS of CIA rats in vivo and vitro.
  
  
  CONCLUSIONS
  Inflammatory mediators and G protein-coupled signaling were associated with the pathogenesis of synovitis in CIA rats. Pae, as a new monomer, had anti-inflammatory effects on the animal model of CIA in rats, but also had regulatory effects on FLS from CIA rats in vitro. These results highlight Pae as a good candidate for therapeutic intervention in RA.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and immuno-pharmacology, Anhui Province, PR China.
authors.forename: L L
authors.initials: LL
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.forename: N P
authors.initials: NP
authors.lastname: Wang
authors.forename: Q T
authors.initials: QT
authors.lastname: Wang
authors.forename: J Y
authors.initials: JY
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: X Y
authors.initials: XY
authors.lastname: Hu
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology*; D008297:Male; D039821:Monoterpenes; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D006027:Glycosides
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001565:Benzoates; D001952:Bridged-Ring Compounds; D019204:GTP-Binding Proteins; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides