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Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage

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Abstract

The saponin astragaloside IV (AST) is one of major active components purified from Astragalus membranaceus (Fisch) Bge, which has been used in traditional Chinese medicine to treat immune disorders including rheumatoid arthritis (RA). The effects of AST on the suppression of experimental arthritis and its possible mechanisms are unknown. We measured the paw swelling of ankle joints, splenocyte proliferation, interleukin 1β (IL-1β), tumor necrosis factor α (TNFα) and nitric oxide (NO) formation by macrophages in rat adjuvant-induced arthritis (AIA). Intraarticular injection of IL-1β to rat knee joint for inducing the edema and in vitro IL-1β-stimulated cartilage impairment were examined. The results showed that oral treatment of AST (100 mg/kg/day) suppressed the joint inflammation and inhibited IL-1β, TNFα and NO production in macrophages from AIA rats. Macrophages were one of AST targeted cells, and mediated the reduced splenocyte proliferation in AIA rats. In addition, AST reduced the swelling induced by intraarticular injection of IL-1β, and protected against IL-1β-induced damage of cartilage proteoglycan synthesis and chondrocyte proliferation. We conclude that AST possesses antiarthritic effect and prevents IL-1β-induced joint inflammation and cartilage destruction. These findings suggest that AST may be used for the treatment of RA and other inflammatory joint diseases.

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References

  • Albina, J.E., J.A. Abate, and W.L. Henry Jr. 1991. Nitric oxide production is required for murine resident peritoneal macrophages to suppress mitogen-stimulated T cell proliferation. Role of IFN-gamma in the induction of the nitric oxide-synthesizing pathway. Journal of Immunology 147: 144–148.

    CAS  Google Scholar 

  • Bao, F., P. Wu, N. Xiao, F. Qiu, and Q.P. Zeng. 2012. Nitric oxide-driven hypoxia initiates synovial angiogenesis, hyperplasia and inflammatory lesions in mice. PLoS One 7: e34494.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bendele, A. 2001. Animal models of rheumatoid arthritis. Journal of Musculoskeletal and Neuronal Interactions 1: 377–385.

    CAS  PubMed  Google Scholar 

  • Chen, D.Y., Y.M. Chen, H.H. Chen, C.W. Hsieh, C.C. Lin, and J.L. Lan. 2011. Increasing levels of circulating Th17 cells and interleukin-17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-alpha therapy. Arthritis Research & Therapy 13: R126.

    Article  CAS  Google Scholar 

  • Cho, W.C., and K.N. Leung. 2007. In vitro and in vivo immunomodulating and immunorestorative effects of Astragalus membranaceus. Journal of Ethnopharmacology 113: 132–141.

    Article  PubMed  Google Scholar 

  • Davignon, J.L., M. Hayder, M. Baron, J.F. Boyer, A. Constantin, F. Apparailly, R. Poupot, and A. Cantagrel. 2013. Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 52: 590–598.

    Article  CAS  Google Scholar 

  • Deknuydt, F., G. Bioley, D. Valmori, and M. Ayyoub. 2009. IL-1beta and IL-2 convert human Treg into T(H)17 cells. Clinical Immunology 131: 298–307.

    Article  CAS  PubMed  Google Scholar 

  • Deng, S., Y. Xi, H. Wang, J. Hao, X. Niu, W. Li, Y. Tao, and G. Chen. 2010. Regulatory effect of vasoactive intestinal peptide on the balance of Treg and Th17 in collagen-induced arthritis. Cellular Immunology 265: 105–110.

    Article  CAS  PubMed  Google Scholar 

  • Evans, H.G., N.J. Gullick, S. Kelly, C. Pitzalis, G.M. Lord, B.W. Kirkham, and L.S. Taams. 2009. In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses. Proceedings of the National Academy of Sciences of the United States of America 106: 6232–6237.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hu, W., L.J. Xia, F.H. Chen, F.R. Wu, J. Tang, C.Z. Chen, S. Jiang, and H.H. Chen. 2012. Recombinant human endostatin inhibits adjuvant arthritis by down-regulating VEGF expression and suppression of TNF-alpha, IL-1beta production. Inflammation Research 61: 827–835.

    Article  CAS  PubMed  Google Scholar 

  • Jiang, J.B., J.D. Qiu, L.H. Yang, J.P. He, G.W. Smith, and H.Q. Li. 2010. Therapeutic effects of astragalus polysaccharides on inflammation and synovial apoptosis in rats with adjuvant-induced arthritis. International Journal of Rheumatic Diseases 13: 396–405.

    Article  PubMed  Google Scholar 

  • Jouzeau, J.Y., C. Cipolletta, N. Presle, P. Netter, and B. Terlain. 1999. Modulation of IL-1 effects on cartilage by NO synthase inhibitors: pharmacological studies in rats. Osteoarthritis Cartilage 7: 382–385.

    Article  CAS  PubMed  Google Scholar 

  • Jovanovic, D.V., L. Boumsell, A. Bensussan, X. Chevalier, A. Mancini, and J.A. Di Battista. 2011. CD101 expression and function in normal and rheumatoid arthritis-affected human T cells and monocytes/macrophages. Journal of Rheumatology 38: 419–428.

    Article  CAS  PubMed  Google Scholar 

  • Ju, J.H., Y.J. Heo, M.L. Cho, J.Y. Jhun, J.S. Park, S.Y. Lee, H.J. Oh, S.J. Moon, S.K. Kwok, K.S. Park, S.H. Park, and H.Y. Kim. 2012. Modulation of STAT-3 in rheumatoid synovial T cells suppresses Th17 differentiation and increases the proportion of Treg cells. Arthritis and Rheumatism 64: 3543–3552.

    Article  CAS  PubMed  Google Scholar 

  • Kinne, R.W., R. Brauer, B. Stuhlmuller, E. Palombo-Kinne, and G.R. Burmester. 2000. Macrophages in rheumatoid arthritis. Arthritis Research 2: 189–202.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lei, H., B. Wang, W.P. Li, Y. Yang, A.W. Zhou, and M.Z. Chen. 2003. Anti-aging effect of astragalosides and its mechanism of action. Acta Pharmacologica Sinica 24: 230–234.

    CAS  PubMed  Google Scholar 

  • Li, H.Q., J.D. Qiu, and L.H. Yang. 2009. Regulation of Astragalus heteropolysaccharides on synoviocytes apoptosis and proinflammatory cytokine secretion of rats with adjuvant arthritis. Yao Xue Xue Bao 44: 731–736.

    PubMed  Google Scholar 

  • Liu, Q.Y., Y.M. Yao, S.W. Zhang, and Z.Y. Sheng. 2011. Astragalus polysaccharides regulate T cell-mediated immunity via CD11c(high)CD45RB(low) DCs in vitro. Journal of Ethnopharmacology 136: 457–464.

    Article  CAS  PubMed  Google Scholar 

  • Ma, X.Q., Q. Shi, J.A. Duan, T.T. Dong, and K.W. Tsim. 2002. Chemical analysis of Radix Astragali (Huangqi) in China: a comparison with its adulterants and seasonal variations. Journal of Agriculture and Food Chemistry 50: 4861–4866.

    Article  CAS  Google Scholar 

  • Nagy, G., A. Koncz, T. Telarico, D. Fernandez, B. Ersek, E. Buzas, and A. Perl. 2010. Central role of nitric oxide in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. Arthritis Research & Therapy 12: 210.

    Article  Google Scholar 

  • Nistala, K., and L.R. Wedderburn. 2009. Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis. Rheumatology (Oxford) 48: 602–606.

    Article  CAS  Google Scholar 

  • Palmer, G., D. Talabot-Ayer, I. Szalay-Quinodoz, M. Maret, W.P. Arend, and C. Gabay. 2003. Mice transgenic for intracellular interleukin-1 receptor antagonist type 1 are protected from collagen-induced arthritis. European Journal of Immunology 33: 434–440.

    Article  CAS  PubMed  Google Scholar 

  • Prati, C., A. Berthelot, B. Kantelip, D. Wendling, and C. Demougeot. 2012. Treatment with the arginase inhibitor Nw-hydroxy-nor-l-arginine restores endothelial function in rat adjuvant-induced arthritis. Arthritis Research & Therapy 14: R130.

    CAS  Google Scholar 

  • Presle, N., C. Cipolletta, J.Y. Jouzeau, A. Abid, P. Netter, and B. Terlain. 1999. Cartilage protection by nitric oxide synthase inhibitors after intraarticular injection of interleukin-1beta in rats. Arthritis and Rheumatism 42: 2094–2102.

    Article  CAS  PubMed  Google Scholar 

  • Schett, G., L.C. Coates, Z.R. Ash, S. Finzel, S. Finzel, and P.G. Conaghan. 2011. Structural damage in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: traditional views, novel insights gained from TNF blockade, and concepts for the future. Arthritis Research & Therapy 13(Suppl 1): S4.

    Google Scholar 

  • Stefanovic-Racic, M., K. Meyers, C. Meschter, J.W. Coffey, R.A. Hoffman, and C.H. Evans. 1994. N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis and Rheumatism 37: 1062–1069.

    Article  CAS  PubMed  Google Scholar 

  • Stefanovic-Racic, M., M.O. Mollers, L.A. Miller, and C.H. Evans. 1997. Nitric oxide and proteoglycan turnover in rabbit articular cartilage. Journal of Orthopaedic Research 15: 442–449.

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi, H. 2007. Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nature Reviews Immunology 7: 292–304.

    Article  CAS  PubMed  Google Scholar 

  • Thirion, S., and F. Berenbaum. 2004. Culture and phenotyping of chondrocytes in primary culture. Methods in Molecular Medicine 100: 1–14.

    PubMed  Google Scholar 

  • Van Bezooijen, R.L., L. Van Der Wee-Pals, S.E. Papapoulos, and C.W. Lowik. 2002. Interleukin 17 synergises with tumour necrosis factor alpha to induce cartilage destruction in vitro. Annals of the Rheumatic Diseases 61: 870–876.

    Article  PubMed Central  PubMed  Google Scholar 

  • Walter, G.J., H.G. Evans, B. Menon, N.J. Gullick, B.W. Kirkham, A.P. Cope, F. Geissmann, and L.S. Taams. 2013. Interaction with activated monocytes enhances cytokine expression and suppressive activity of human CD4 + CD45ro + CD25 + CD127(low) regulatory T cells. Arthritis and Rheumatism 65: 627–638.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang, B., and M.Z. Chen. 1998. Effects of indomethacin on secretory function of synoviocytes from adjuvant arthritis rats. International Journal of Tissue Reactions 20: 91–94.

    CAS  PubMed  Google Scholar 

  • Wang, B., L. Ma, X. Tao, and P.E. Lipsky. 2004. Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis and Rheumatism 50: 303–2995.

    Google Scholar 

  • Wang, B., Y.Y. Yao, and M.Z. Chen. 1998. Effects of indomethacin on joint damage in rat and rabbit. Zhongguo Yao Li Xue Bao 19: 70–73.

    CAS  PubMed  Google Scholar 

  • Wang, Y.P., X.Y. Li, C.Q. Song, and Z.B. Hu. 2002. Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice. Acta Pharmacologica Sinica 23: 263–266.

    PubMed  Google Scholar 

  • Yang, L.H., J.D. Qiu, and H.Q. Li. 2009. Effects of Astragalus heteropolysaccharides on erythrocyte immune adherence function of mice with adjuvant-induced arthritis. Yao Xue Xue Bao 44: 1364–1370.

    PubMed  Google Scholar 

  • Yao, R., Y. Fu, S. Li, L. Tu, X. Zeng, and N. Kuang. 2011. Regulatory effect of daphnetin, a coumarin extracted from Daphne odora, on the balance of Treg and Th17 in collagen-induced arthritis. European Journal of Pharmacology 670: 286–294.

    Article  CAS  PubMed  Google Scholar 

  • Yu, Q.T., L.W. Qi, P. Li, L. Yi, J. Zhao, and Z. Bi. 2007. Determination of seventeen main flavonoids and saponins in the medicinal plant Huang-qi (Radix astragali) by HPLC-DAD-ELSD. Journal of Separation Science 30: 1292–1299.

    Article  CAS  PubMed  Google Scholar 

  • Zivojinovic, S.M., N.N. Pejnovic, M.N. Sefik-Bukilica, L.V. Kovacevic, Ii Soldatovic, and N.S. Damjanov. 2012. Tumor necrosis factor blockade differentially affects innate inflammatory and Th17 cytokines in rheumatoid arthritis. Journal of Rheumatology 39: 18–21.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We would like to thank Wei-Ping Li and Ai-Wu Zhou for their excellent technical assistances.

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Authors and Affiliations

  1. Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, W-1303 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA, 15261, USA

    Bin Wang

  2. Institute of Clinical Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, People’s Republic of China

    Min-Zhu Chen

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  1. Bin Wang
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Correspondence to Bin Wang.

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Wang, B., Chen, MZ. Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage. Arch. Pharm. Res. 37, 793–802 (2014). https://doi.org/10.1007/s12272-014-0336-2

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