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Effect and mechanism of AR-6 in experimental rheumatoid arthritis

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Abstract

The root of Clematis chinensis Osbeck has been used widely in rheumatoid arthritis in Chinese traditional medicine and AR-6 is a triterpene saponin isolated from it. In this present study, we investigated in vivo effects of oral AR-6 in chronic rat adjuvant-induced arthritis (AA) and in vitro effect in macrophage and synoviocytes cells. Arthritic scores and serum inflammatory mediators were evaluated 19 days after AA induction by endermic injection of Freund’s complete adjuvant in Sprague-Dawley(S-D) rats. Oral administration of AR-6 to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. The synoviocyte and macrophage response ex vivo were then analyzed. Anti-arthritic effects of AR-6 correlated with significant decrease of NO and TNF-α produced by peritoneal macrophages, ex vivo and in vitro. AR-6 also significant decreased the proliferation of synoviocyte. These data indicate that AR-6 is a potential anti-inflammatory therapeutic and preventive agent.

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References

  1. Sweeney SEFG (2004) Rheumatoid arthritis: regulation of synovial inflammation. Int J Biochem Cell Biol 36:372–378

    Article  CAS  PubMed  Google Scholar 

  2. Tak PPST, Daha MR, Kluin PM, Meijers KA, Brand R et al (1997) Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum 40:217–225

    Article  CAS  PubMed  Google Scholar 

  3. Choy EHPG (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907–916

    Article  CAS  PubMed  Google Scholar 

  4. Mulherin DFO, Bresnihan B (1996) Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum 39:115–124

    Article  CAS  PubMed  Google Scholar 

  5. Sano HHT, Maier JA, Crofford LJ, Case JP, Maciag T et al (1992) In vivo cyclooxygenase expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis and rats with adjuvant and streptococcal cell wall arthritis. J Clin Invest 89:97–108

    Article  CAS  PubMed  Google Scholar 

  6. Miyasaka NHY (1997) Nitric oxide and inflammation arthritides. Life Sci 61:2073–2081

    Article  CAS  PubMed  Google Scholar 

  7. Farrell AJBD, Palmer RM, Moncada S (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51:1219–1222

    Article  CAS  PubMed  Google Scholar 

  8. Ueki YMS, Tominaga Y, Eguchi K (1996) Increased nitric oxide levels in patients with rheumatoid arthritis. J Rheumatol 23:230–236

    CAS  PubMed  Google Scholar 

  9. Clair St EWWW, Lang T, Sanders L, Misukonis MA, Gilkeson GS et al (1996) Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis patients. J Exp Med 184:1173–1178

    Article  Google Scholar 

  10. Mamani-Matsuda M, Kauss T, Abir Al-Kharrat J (2006) Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators. Biochem Pharmacol doi:10.1016/j.bcp.2006.08.001

  11. Youn J, Cho M-L, Kim Y-J, Yun HS, Park S-H, Jin C-Z, Paik D-J, Kim H-Y (2005) New cyclooxygenase-2 inhibitor DFU regulates vascular endothelial growth factor expression in rheumatoid synoviocytes. Immunol Lett 96:219–224

    Article  CAS  PubMed  Google Scholar 

  12. Takahashi KKH, Kobayashi S, Kimura I, Terasawa K et al (1996) Antiproliferative effects of magnosalin derived from ‘shin-I’, a Japanese sinomedicine, on cultured synovial cells of MRL/1 and C57BL/6 J mice. Phytother Res 10:42–48

    Article  CAS  Google Scholar 

  13. Warren JS (1990) Interleukins and tumor necrosis factor in inflammation. Crit Rev Clin Lab Sci 28:37–59

    Article  CAS  PubMed  Google Scholar 

  14. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361

    Article  CAS  PubMed  Google Scholar 

  15. Goronzy JJ (2005) Rheumatoid arthritis. Immunol Rev 204:55–73

    Article  CAS  PubMed  Google Scholar 

  16. Arend WP (1995) Inhibition of the production and effects of IL-1and TNF-α in RA. Arthritis Rheum 38:151–160

    Article  CAS  PubMed  Google Scholar 

  17. Choy EHS, Panayi GS (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. New Engl J Med 344:907–916

    Article  CAS  PubMed  Google Scholar 

  18. Takeuchi T, Nakanishi T et al (2007) Serum protein profile of rheumatoid arthritis treated with anti-TNF therapy (infliximab). J Chromatogr B 855:66–70

    Article  CAS  Google Scholar 

  19. Hirano T (1992) The biology of interleukin-6. Chem Immunol 51:153–180

    Article  CAS  PubMed  Google Scholar 

  20. Tan PL, Farmiloe S, Yeoman S, Watson JD (1990) Expression of the interleukin 6 gene in rheumatoid synovial fibroblasts. J Rheumatol 17:1608–1612

    CAS  PubMed  Google Scholar 

  21. Van’t Hof RJHL, Wright PK, Ralston SH (2000) Nitric oxide is a mediator of apoptosis in the rheumatoid joint. Rheumatology 39:1004–1008

    Article  PubMed  Google Scholar 

  22. McCartney-Francis NAJ, Mizel DE, Albina JE, Xie QW, Nathan CF et al (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178:749–754

    Article  CAS  PubMed  Google Scholar 

  23. Simon LSW, Graham DY et al (1999) Anti-inflammatory and upper gastrointestinal effects of Celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 282:1921–1928

    Article  CAS  PubMed  Google Scholar 

  24. Myers LKK, Postlethwaite AE et al (2000) The genetic ablation of cyclooxygenase 2 prevents the development of autoimmune arthritis. Arthritis Rheum 42:2687–2693

    Article  Google Scholar 

  25. LG R (1999) Prostaglandins and bone: physiology and pathophysiology. Osteoarthritis Cartilage 7:419–421

    Article  Google Scholar 

  26. Ma Y, Pope R (2005) The role of macrophages in rheumatoid arthritis. Curr Pharm Des 11:569–580

    Article  CAS  PubMed  Google Scholar 

  27. Folkman J (1995) Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1:27–31

    Article  CAS  PubMed  Google Scholar 

  28. Mamani-Matsuda M, Rambert J, Malvy D, Lejoly-Boisseau H, Daulouede S, Thiolat D et al (2004) Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages. Antimicrob Agents Chemother 48:924–929

    Article  CAS  PubMed  Google Scholar 

  29. Hammaker DSS, Firestein GS (2003) Signal transduction networks in rheumatoid arthritis. Ann Rheum Dis 62:86–89

    Article  Google Scholar 

  30. Taylor PC (2003) Anti-cytokines and cytokines in the treatment of rheumatoid arthritis. Curr Pharm Des 9:1095–1106

    Article  CAS  PubMed  Google Scholar 

  31. Feldmann M (1996) The cytokine network in rheumatoid arthritis:definition of TNF alpha as a therapeutic target. J R Coll Physicians Lond 30:560–570

    CAS  PubMed  Google Scholar 

  32. Tanaka Y (2001) The role of chemokines and adhesion molecules in the pathogenesis of rheumatoid arthritis. Drugs Today 37:477–484

    Article  CAS  PubMed  Google Scholar 

  33. Latha MR, Geetha T, Varalakshmi P (1998) Effect of Vernonia cinerea less flower extract in adjuvant-induced arthritis. Gen Pharmacol Res 31:601–606

    Article  CAS  Google Scholar 

  34. Di Giovine FS, Nuki G, Duff W (1988) Tumour necrosis factor in synovial exudates. Ann Rheum Dis 47:768–772

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank professor Yu-xin Wang and Department of Pharmaceutical, School of Traditional Chinese Pharmacy, China Pharmaceutical University.

Conflict of interest statement

The authors declare that they have no conflict of interest to the publication of this manuscript.

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Authors and Affiliations

  1. Department of Physiology, China Pharmaceutical University, 210009, Nanjing, China

    Shi-xue Sun, Yun-man Li, Wei-rong Fang & Peng Cheng

  2. Department of Pharmacognosy and the Key Laboratory of Modern Chinese Medicines, Ministry of Education, China Pharmaceutical University, 210038, Nanjing, China

    Lifang Liu

  3. Department of Traditional Chinese Pharmacy, China Pharmaceutical University, 210038, Nanjing, China

    Fengwen Li

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  1. Shi-xue Sun
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  2. Yun-man Li
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  3. Wei-rong Fang
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Correspondence to Yun-man Li.

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Sun, Sx., Li, Ym., Fang, Wr. et al. Effect and mechanism of AR-6 in experimental rheumatoid arthritis. Clin Exp Med 10, 113–121 (2010). https://doi.org/10.1007/s10238-009-0075-8

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  • DOI: https://doi.org/10.1007/s10238-009-0075-8

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