Skip to main content

Advertisement

SpringerLink
Log in

Tormentic Acid Inhibits IL-1β-Induced Inflammatory Response in Human Osteoarthritic Chondrocytes

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The pro-inflammatory cytokine interleukin-1beta (IL-1β) plays critical roles in pathogenesis of osteoarthritis (OA). Tormentic acid (TA), a triterpene isolated from Rosa rugosa, has anti-inflammatory activity. However, the anti-inflammatory effect of TA on OA is still unclear. So, in the present study, we examined the effect of TA on IL-1β-induced inflammatory response in primary human OA chondrocytes. Our results demonstrated that TA significantly decreased the IL-1β-stimulated expression of matrix metalloproteinase-3 (MMP-3) and MMP-13. It also inhibited the IL-1β-induced expression of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the production of NO and prostaglandin E2 (PGE2) in human OA chondrocytes. Furthermore, TA greatly inhibited the IL-1β-induced NF-κB activation. In conclusion, this study is the first to demonstrate the anti-inflammatory activity of TA in human OA chondrocytes. TA significantly inhibits the IL-1β-induced inflammatory response by suppressing the NF-κB signaling pathway. Thus, TA may be a potential agent in the treatment of OA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

REFERENCES

  1. Loeser, R.F. 2009. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Osteoarthritis and Cartilage 17: 971–979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Corti, M.C., and C. Rigon. 2003. Epidemiology of osteoarthritis: prevalence, risk factors and functional impact. Aging Clinical and Experimental Research 15: 359–363.

    Article  PubMed  Google Scholar 

  3. Pelletier, J.P., J. Martel‐Pelletier, and S.B. Abramson. 2001. Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis and Rheumatism 44: 1237–1247.

    Article  CAS  PubMed  Google Scholar 

  4. Loeser, R.F. 2006. Molecular mechanisms of cartilage destruction: mechanics, inflammatory mediators, and aging collide. Arthritis and Rheumatism 54: 1357–1360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wenliang, Z., L. Rongheng, W. Shumei, M. Fangzheng, and J. Ping. 2013. Effect of Chinese traditional herb Epimedium grandiflorum C. Morren and its extract Icariin on osteoarthritis via suppressing NF-KB pathway. Indian Journal of Experimental Biology 51: 313–321.

    Google Scholar 

  6. Chen, M., S. Yang, C. Chou, K. Yang, C. Wu, Y. Cheng, et al. 2010. The chondroprotective effects of ferulic acid on hydrogen peroxide-stimulated chondrocytes: inhibition of hydrogen peroxide-induced pro-inflammatory cytokines and metalloproteinase gene expression at the mRNA level. Inflammation Research 59: 587–595.

    Article  CAS  PubMed  Google Scholar 

  7. Toegel, S., S. Wu, C. Piana, F. Unger, M. Wirth, M. Goldring, et al. 2008. Comparison between chondroprotective effects of glucosamine, curcumin, and diacerein in IL-1β-stimulated C-28/I2 chondrocytes. Osteoarthritis and Cartilage 16: 1205–1212.

    Article  CAS  PubMed  Google Scholar 

  8. Fogo, A.S., E. Antonioli, J.B. Calixto, and A.H. Campos. 2009. Tormentic acid reduces vascular smooth muscle cell proliferation and survival. European Journal of Pharmacology 615: 50–54.

    Article  CAS  PubMed  Google Scholar 

  9. Wu, J.-B., Y.-H. Kuo, C.-H. Lin, H.-Y. Ho, and C.-C. Shih. 2014. Tormentic acid, a major component of suspension cells of Eriobotrya japonica, suppresses high-fat diet-induced diabetes and hyperlipidemia by glucose transporter 4 and AMP-activated protein kinase phosphorylation. Journal of Agricultural and Food Chemistry 62: 10717–10726.

    Article  CAS  PubMed  Google Scholar 

  10. Banno, N., T. Akihisa, H. Tokuda, K. Yasukawa, H. Higashihara, M. Ukiya, et al. 2004. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Bioscience Biotechnology and Biochemistry 68: 85–90.

    Article  CAS  Google Scholar 

  11. Lin, X., S. Zhang, R. Huang, S. Tan, S. Liang, X. Wu, et al. 2014. Protective effect of tormentic acid from Potentilla chinensis against lipopolysaccharide/D-galactosamine induced fulminant hepatic failure in mice. International Immunopharmacology 19: 365–372.

    Article  CAS  PubMed  Google Scholar 

  12. Jian, C.-X., M.-Z. Li, W.-Y. Zheng, Y. He, Y. Ren, Z.-M. Wu, et al. 2015. Tormentic acid inhibits LPS-induced inflammatory response in human gingival fibroblasts via inhibition of TLR4-mediated NF-κB and MAPKs signaling pathway. Archives of Oral Biology 60: 1327–1332.

    Article  CAS  PubMed  Google Scholar 

  13. Cheng, A.W.M., T.V. Stabler, M. Bolognesi, and V.B. Kraus. 2011. Selenomethionine inhibits IL-1β inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes. Osteoarthritis and Cartilage 19: 118–125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Au, R., T. Al-Talib, A. Au, P. Phan, and C. Frondoza. 2007. Avocado soybean unsaponifiables (ASU) suppress TNF-α, IL-1β, COX-2, iNOS gene expression, and prostaglandin E 2 and nitric oxide production in articular chondrocytes and monocyte/macrophages. Osteoarthritis and Cartilage 15: 1249–1255.

    Article  CAS  PubMed  Google Scholar 

  15. Martel-Pelletier, J., D.J. Welsch, and J.-P. Pelletier. 2001. Metalloproteases and inhibitors in arthritic diseases. Best Practice & Research. Clinical Rheumatology 15: 805–829.

    Article  CAS  Google Scholar 

  16. Koskinen, A., K. Vuolteenaho, R. Nieminen, T. Moilanen, and E. Moilanen. 2010. Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clinical and Experimental Rheumatology 29: 57–64.

    Google Scholar 

  17. Santangelo, K., G. Nuovo, and A. Bertone. 2012. In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis. Osteoarthritis and Cartilage 20: 1610–1618.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Aktan, F. 2004. iNOS-mediated nitric oxide production and its regulation. Life Sciences 75: 639–653.

    Article  CAS  PubMed  Google Scholar 

  19. Sasaki, K., T. Hattori, T. Fujisawa, K. Takahashi, H. Inoue, and M. Takigawa. 1998. Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes. Journal of Biochemistry 123: 431–439.

    Article  CAS  PubMed  Google Scholar 

  20. Goggs, R., S.D. Carter, G. Schulze-Tanzil, M. Shakibaei, and A. Mobasheri. 2003. Apoptosis and the loss of chondrocyte survival signals contribute to articular cartilage degradation in osteoarthritis. The Veterinary Journal 166: 140–158.

    Article  CAS  PubMed  Google Scholar 

  21. Li, N., M.A. Rivéra-Bermúdez, M. Zhang, J. Tejada, S.S. Glasson, L.A. Collins-Racie, et al. 2010. LXR modulation blocks prostaglandin E2 production and matrix degradation in cartilage and alleviates pain in a rat osteoarthritis model. Proceedings of the National Academy of Sciences 107: 3734–3739.

    Article  CAS  Google Scholar 

  22. Ahmed, S., A. Rahman, A. Hasnain, M. Lalonde, V.M. Goldberg, and T.M. Haqqi. 2002. Green tea polyphenol epigallocatechin-3-gallate inhibits the IL-1β-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes. Free Radical Biology and Medicine 33: 1097–1105.

    Article  CAS  PubMed  Google Scholar 

  23. Fahmi, H., J.A. Di Battista, J.P. Pelletier, F. Mineau, P. Ranger, and J. Martel‐Pelletier. 2001. Peroxisome proliferator–activated receptor γ activators inhibit interleukin‐1β–induced nitric oxide and matrix metalloproteinase 13 production in human chondrocytes. Arthritis and Rheumatism 44: 595–607.

    Article  CAS  PubMed  Google Scholar 

  24. Chabane, N., N. Zayed, H. Afif, L. Mfuna-Endam, M. Benderdour, C. Boileau, et al. 2008. Histone deacetylase inhibitors suppress interleukin-1β-induced nitric oxide and prostaglandin E 2 production in human chondrocytes. Osteoarthritis and Cartilage 16: 1267–1274.

    Article  CAS  PubMed  Google Scholar 

  25. An, H.-J., I.-T. Kim, H.-J. Park, H.-M. Kim, J.-H. Choi, and K.-T. Lee. 2011. Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited LPS-induced iNOS, COX-2, and TNF-α expression through inactivation of the nuclear factor-κb pathway in RAW 264.7 macrophages. International Immunopharmacology 11: 504–510.

    Article  CAS  PubMed  Google Scholar 

  26. Blackwell, T.S., and J.W. Christman. 1997. The role of nuclear factor-κ B in cytokine gene regulation. American Journal of Respiratory Cell and Molecular Biology 17: 3–9.

    Article  CAS  PubMed  Google Scholar 

  27. Tak, P.P., and G.S. Firestein. 2001. NF-κB: a key role in inflammatory diseases. Journal of Clinical Investigation 107: 7–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wehling, N., G. Palmer, C. Pilapil, F. Liu, J. Wells, P. Müller, et al. 2009. Interleukin‐1β and tumor necrosis factor α inhibit chondrogenesis by human mesenchymal stem cells through NF‐κB–dependent pathways. Arthritis and Rheumatism 60: 801–812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang, S.-N., G.-P. Xie, C.-H. Qin, Y.-R. Chen, K.-R. Zhang, X. Li, et al. 2015. Aucubin prevents interleukin-1 beta induced inflammation and cartilage matrix degradation via inhibition of NF-κB signaling pathway in rat articular chondrocytes. International Immunopharmacology 24: 408–415.

    Article  PubMed  Google Scholar 

  30. Liacini, A., J. Sylvester, W.Q. Li, and M. Zafarullah. 2002. Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-κB) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biology 21: 251–262.

    Article  CAS  PubMed  Google Scholar 

  31. Lianxu, C., J. Hongti, and Y. Changlong. 2006. NF-κBp65-specific siRNA inhibits expression of genes of COX-2, NOS-2 and MMP-9 in rat IL-1β-induced and TNF-α-induced chondrocytes. Osteoarthritis and Cartilage 14: 367–376.

    Article  CAS  PubMed  Google Scholar 

  32. Ma, A., Y. Wang, and Q. Zhang. 2015. Tormentic acid reduces inflammation in BV-2 microglia by activating the liver X receptor alpha. Neuroscience 287: 9–14.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was funded by the project of National Natural Science Foundation of China (81501919).

Author information

Author notes

    Authors and Affiliations

    1. Department of Orthopedics, Tianjin Hospital, Tianjin, 300211, China

      Yang Yang, Yumin Wang, Haobo Jia & Bing Li

    2. Department of Electromyography, Tianjin Hospital, Tianjin, 300211, China

      Yawei Wang

    3. Clinical laboratory, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China

      Meng Zhao

    4. Arthritis Clinic & Research Center, Peking University People’s Hospital, Peking University, Beijing, 100044, China

      Dan Xing

    Authors
    1. Yang Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yawei Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Yumin Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Meng Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Haobo Jia
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Bing Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Dan Xing
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Bing Li or Dan Xing.

    Additional information

    Yang Yang and Yawei Wang contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Yang, Y., Wang, Y., Wang, Y. et al. Tormentic Acid Inhibits IL-1β-Induced Inflammatory Response in Human Osteoarthritic Chondrocytes. Inflammation 39, 1151–1159 (2016). https://doi.org/10.1007/s10753-016-0349-8

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10753-016-0349-8

    KEY WORDS

    Search

    Navigation