title: Anti-arthritic activity of Fu-Fang-Lu-Jiao-Shuang on collagen-induced arthritis in Balb/c mice and its underlying mechanisms.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is a common, autoimmune disorder characterized by progressive multiple joint destruction, deformity, disability and premature death in most patients. Fu-Fang-Lu-Jiao-Shuang (FFLJS) is an effective traditional Chinese medicine, which has long been used clinically to treat RA patients.
  
  
  OBJECTIVE
  The objective of this study is aimed to evaluate the anti-rheumatic effects of FFLJS on collagen induced arthritis (CIA) model, as well as the underlying mechanisms, which have not previously been explored.
  
  
  METHODS
  CIA was induced by immunization with type II collagen (CII) in male Balb/c mice. The mice in the onset of arthritis were treated daily with FFLJS (125 or 500 mg/kg) or 1% carboxymethyl cellulose-Na for 28 days. Paw thickness and arthritic score were evaluated to confirm the anti-arthritic effect of FFLJS on CIA in mice. Levels of anti-CII antibody, proinflammatory cytokines interleukin-1 (IL-1) β, IL-17, and tumor necrosis factor-α (TNF-α) as well as prostaglandin E-2 (PGE-2) in serum and histological changes in the ankle joint were also analyzed. In addition, expressions of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitors of matrix metalloproteases-1 (TIMP-1) in synovial tissue were also detected to further study the molecular mechanism of the anti-arthritic effects of FFLJS.
  
  
  RESULTS
  During therapeutic treatment, FFLJS significantly reduced paw thickness and arthritic score in CIA mice, decreased the amounts of TNF-α, IL-1 β, IL-17, PGE-2 and anti-CII antibody in serum. In addition, FFLJS treatment could prevent the bone destruction by reducing the expression of MMP-1 and MMP-3, increasing the expression of TIMP-1 in synovial tissue of CIA mice.
  
  
  CONCLUSIONS
  These findings offer the convincing evidence for the first time that the anti-rheumatic effects of FFLJS might be related to down-regulation of TNF-α, IL-1 β, IL-17 and PGE-2 levels for acute arthritis, and regulation of MMP-1, MMP-3 and TIMP-1 protein expression for chronic arthritis.
authors.affiliation: Department of Pharmacology, Yichang Central People's Hospital, Sanxia University, Yichang, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Tongji Medical College, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Yichang Central People's Hospital, Sanxia University, Yichang, China.
authors.forename: Laxia
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Tongji Medical College, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Tongji Medical College, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jinwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Tongji Medical College, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
keywords: Anti-arthritic activity; Fu-Fang-Lu-Jiao-Shuang; matrix metalloproteinases; traditional Chinese medicine
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