title: The suppressive effects of Saposhnikovia divaricata (Fangfeng) chromone extract on rheumatoid arthritis via inhibition of nuclear factor-κB and mitogen activated proteinkinases activation on collagen-induced arthritis model.
abstract: BACKGROUND
  Saposhnikovia divaricata (SD), called "Fangfeng" in China, is commonly used in clinical compound prescription for treatment of rheumatoid arthritis (RA), but its actions on RA have not been clarified. The present study aims to determine the anti-inflammatory activity of SD chromone extract (SCE), the major bioactive component of SD, on collagen-induced arthritis (CIA) rats, and elucidate its underlying mechanisms with regards to its molecular basis of action on human fibroblast-like synoviocytes derived from RA patients (HFLS-RA).
  
  
  METHODS
  CIA model on rats was constructed by injection of bovine type II collagen. Rats were pre-treated with different dosages of SCE from 3 days before till 35 days after model building. The progression of CIA was evaluated by macroscopic scoring, X-ray observation and hematoxylin and eosin (HE) staining of paws. HFLS-RA were pre-treated with different concentrations of SCE prior to stimulation with 10 ng/ml of tumor necrosis factor (TNF) α. By radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), levels of interleukin (IL)-1β, IL-6, TNFα and prostaglandin E2 (PGE2) were quantified respectively. Nuclear factor (NF-κB) p65 expression and DNA-binding activity were tested by immunohistochemisty and electrophoretic mobility shift assay (EMSA) respectively. Phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPKs were examined by immunohistochemisty staining and western blot analysis.
  
  
  RESULTS
  Histological examination and radiological observation demonstrated that SCE significantly reduced the inflammatory responses in the joints of CIA rats. SCE inhibited the production of TNFα, IL-1β, and IL-6 in the joint tissues and sera. The level of PGE2 in sera was also decreased by SCE. Moreover, SCE treatment in vivo was able to reduce protein level of NF-κB, the transcriptional factor closely related to the inflammatory process, in articular synovium and cartilage of CIA rats. In addition, SCE inhibited p-ERK, p-JNK and p-p38 expression, which were considered to be involved in the phosphorylation of transcription factor NF-κB and the transcription of pro-inflammatory factors. Further, SCE inhibited NF-κB DNA binding activity and attenuated the phosphorylation of ERK, JNK and p38 MAPKs, in a concentration-dependent manner in cultured HFLS-RA.
  
  
  CONCLUSIONS
  These results highlight the anti-arthritic potential of SCE, and provide further evidence of the involvement of the NF-κB and MARKs inhibition in the effects of SCE.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Kong
authors.forename: Chunfang
authors.initials: C
authors.lastname: Liu
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Wang
authors.forename: Hongye
authors.initials: H
authors.lastname: Wan
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Weiheng
authors.initials: W
authors.lastname: Chen
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Xiao
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019661:Apiaceae; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D002867:Chromones; D016207:Cytokines; D016328:NF-kappa B; D010936:Plant Extracts; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone
keywords: Chromones; Mitogen activated proteinkinases; Nuclear factor-kappa B; Saposhnikovia divaricata; rheumatoid arthritis