title: Anti-arthritic effects of clematichinenoside (AR-6) on PI3K/Akt signaling pathway and TNF-α associated with collagen-induced arthritis.
abstract: BACKGROUND
  Clematichinenoside (AR-6) is a triterpene saponin from an anti-arthritic herbal formula Wei-Ling-Xian in Chinese, which is an herbal medicine derived from the dried root and rhizome of Clematis chinensis Osbeck, C. hexapetala Pall., or C. manshurica Rupr. (Ranunculaceae).
  
  
  OBJECTIVE
  To investigate the modulating effect and explored the potential mechanism of AR-6 in rheumatoid arthritis (RA), using collagen-induced arthritis (CIA) in a rat model.
  
  
  METHODS
  CIA was evaluated by measuring body weight, paw swelling and organ index. Expression of TNF-α, PI3K and p-Akt in synovium tissue was measured by immunohistochemistry. Furthermore, expression of TNF-α mRNA, PI3K mRNA and p-Akt mRNA was measured with RT-PCR.
  
  
  RESULTS
  The intragastric administration of AR-6 (32, 16 and 8 mg/kg), especially the high dose level of 32 mg/kg, significantly suppressed the swelling of hind paws of CIA rats (p < 0.01) and inhibited their body weight loss (p < 0.01). Based on histopathological observation, all AR-6 groups showed great amelioration compared with model group. Moreover, AR-6 significantly reduced the production of TNF-α, PI3K and p-Akt expression by immunohistochemistry (p < 0.01), and decreased TNF-α mRNA, PI3K mRNA and p-Akt mRNA in CIA rat synovium (p < 0.01).
  
  
  CONCLUSIONS
  Our study indicates the mechanism of AR-6 is associated with PI3K/Akt signaling pathway and TNF-α.
  
  
  CONCLUSIONS
  Such characteristics relating to AR-6 curing chronic inflammation of CIA, may be effectively applied to the therapeutic potential in patients with inactive RA.
authors.affiliation: Department of Physiology and Pharmacology, China Pharmaceutical University, Nanjing, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Han
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiong
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
authors.forename: Weirong
authors.initials: W
authors.lastname: Fang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Lifang
authors.initials: L
authors.lastname: Liu
authors.forename: Fengwen
authors.initials: F
authors.lastname: Li
authors.forename: Xingxiang
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D039324:Clematis; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012503:Saponins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D012333:RNA, Messenger; C541813:Radix clematidis extract; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; C581539:clematichinenoside; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt