Skip to main content
Log in

Tenuigenin Prevents IL-1β-induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing PI3K/AKT/NF-κB Signaling Pathway

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

Abstract

Tenuigenin (TEN), the main active component of Polygala tenuifolia, has been reported to have anti-inflammatory effects. However, the effects of TEN on IL-1β-stimulated osteoarthritis chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and mechanism of TEN on IL-1β-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with or without TEN for 1 h and then stimulated with IL-1β. The production of NO and PGE2 were detected by the Griess reagent and ELISA. The expression of NF-κB and MAPKs (p38, JNK, ERK) were measured by Western blot analysis. The production of MMP-1, MMP3, and MMP13 were measured by ELISA. The results showed that treatment of TEN significantly inhibited IL-1β-induced NO and PGE2 production. TEN also suppressed IL-1β-induced MMP-1, MMP3, and MMP13 expression. Furthermore, TEN was found to inhibit IL-1β-induced NF-κB activation, PI3K, and AKT phosphorylation. In conclusion, these results suggest that TEN inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by inhibiting PI3K/AKT/NF-κB signaling pathway.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

References

  1. Benito, M.J., D.J. Veale, O. FitzGerald, W.B. van den Berg, and B. Bresnihan. 2005. Synovial tissue inflammation in early and late osteoarthritis. Annals of the Rheumatic Diseases 64: 1263–1267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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 & Rheumatism 44: 1237–1247.

    Article  CAS  Google Scholar 

  3. Pelletier, J.-P., F. Mineau, P. Ranger, G. Tardif, and J. Martel-Pelletier. 1996. The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthritis and Cartilage 4: 77–84.

    Article  CAS  PubMed  Google Scholar 

  4. Kobayashi, M., G.R. Squires, A. Mousa, M. Tanzer, D.J. Zukor, J. Antoniou, U. Feige, and A.R. Poole. 2005. Role of interleukin‐1 and tumor necrosis factor α in matrix degradation of human osteoarthritic cartilage. Arthritis & Rheumatism 52: 128–135.

    Article  CAS  Google Scholar 

  5. Kapoor, M., J. Martel-Pelletier, D. Lajeunesse, J.-P. Pelletier, and H. Fahmi. 2011. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews. Rheumatology 7: 33–42.

    Article  CAS  PubMed  Google Scholar 

  6. Amin, A.R., M. Dave, M. Attur, and S.B. Abramson. 2000. COX-2, NO, and cartilage damage and repair. Current Rheumatology Reports 2: 447–453.

    Article  CAS  PubMed  Google Scholar 

  7. Yang, G., H.-J. Im, and J.H.-C. Wang. 2005. Repetitive mechanical stretching modulates IL-1β induced COX-2, MMP-1 expression, and PGE 2 production in human patellar tendon fibroblasts. Gene 363: 166–172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Burrage, P.S., K.S. Mix, and C.E. Brinckerhoff. 2006. Matrix metalloproteinases: role in arthritis. Frontiers in Bioscience 11: 529–543.

    Article  CAS  PubMed  Google Scholar 

  9. Silverstein, F.E., G. Faich, J.L. Goldstein, L.S. Simon, T. Pincus, A. Whelton, R. Makuch, G. Eisen, N.M. Agrawal, and W.F. Stenson. 2000. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 284: 1247–1255.

    Article  CAS  PubMed  Google Scholar 

  10. Liang, Z., F. Shi, Y. Wang, L. Lu, Z. Zhang, X. Wang, and X. Wang. 2011. Neuroprotective effects of tenuigenin in a SH-SY5Y cell model with 6-OHDA-induced injury. Neuroscience Letters 497: 104–109.

    Article  CAS  PubMed  Google Scholar 

  11. Yuan, H.L., B. Li, J. Xu, Y. Wang, Y. He, Y. Zheng, and X.M. Wang. 2012. Tenuigenin protects dopaminergic neurons from inflammation‐mediated damage induced by the lipopolysaccharide. CNS Neuroscience & Therapeutics 18: 584–590.

    Article  CAS  Google Scholar 

  12. Cai, Z.-L., C.-Y. Wang, X.-Y. Gu, N.-J. Wang, J.-J. Wang, W.-X. Liu, P. Xiao, and C.-H. Li. 2013. Tenuigenin ameliorates learning and memory impairments induced by ovariectomy. Physiology & Behavior 118: 112–117.

    Article  CAS  Google Scholar 

  13. Chen, Y., X. Huang, W. Chen, N. Wang, and L. Li. 2012. Tenuigenin promotes proliferation and differentiation of hippocampal neural stem cells. Neurochemical Research 37: 771–777.

    Article  CAS  PubMed  Google Scholar 

  14. Lv H, Zhu C, Liao Y, Gao Y, Lu G, Zhong W, Zheng Y, Chen W, Ci X. 2015. Tenuigenin ameliorates acute lung injury by inhibiting NF-κB and MAPK signalling pathways. Respiratory Physiology & Neurobiology 216: 43–51.

  15. Cheng, A.W., T.V. Stabler, M. Bolognesi, and V.B. Kraus. 2011. Selenomethionine inhibits IL-1beta 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 

  16. Fukui, N., Y. Zhu, W.J. Maloney, J. Clohisy, and L.J. Sandell. 2003. Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-α in normal and osteoarthritic chondrocytes. The Journal of Bone & Joint Surgery 85: 59–66.

    Article  Google Scholar 

  17. Daheshia, M., and J.Q. Yao. 2008. The interleukin 1β pathway in the pathogenesis of osteoarthritis. The Journal of Rheumatology 35: 2306–2312.

    Article  CAS  PubMed  Google Scholar 

  18. Jacques, C., M. Gosset, F. Berenbaum, and C. Gabay. 2006. The role of IL‐1 and IL‐1Ra in joint inflammation and cartilage degradation. Vitamins & Hormones 74: 371–403.

    Article  CAS  Google Scholar 

  19. Goldring, M.B., and F. Berenbaum. 2004. The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clinical Orthopaedics and Related Research 427: S37–S46.

    Article  PubMed  Google Scholar 

  20. Studer, R., D. Jaffurs, M. Stefanovic-Racic, P. Robbins, and C. Evans. 1999. Nitric oxide in osteoarthritis. Osteoarthritis and Cartilage 7: 377–379.

    Article  CAS  PubMed  Google Scholar 

  21. Futani, H., A. Okayama, K. Matsui, S. Kashiwamura, T. Sasaki, T. Hada, K. Nakanishi, H. Tateishi, S. Maruo, and H. Okamura. 2002. Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation. Journal of Immunotherapy 25: S61–S64.

    Article  CAS  PubMed  Google Scholar 

  22. Karan, A., M.A. Karan, P. Vural, N. Erten, C. Taşçıoğlu, C. Aksoy, M. Canbaz, and A. Öncel. 2003. Synovial fluid nitric oxide levels in patients with knee osteoarthritis. Clinical Rheumatology 22: 397–399.

    Article  PubMed  Google Scholar 

  23. 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 

  24. Baker, R.G., M.S. Hayden, and S. Ghosh. 2011. NF-κB, inflammation, and metabolic disease. Cell Metabolism 13: 11–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lawrence, T., and C. Fong. 2010. The resolution of inflammation: anti-inflammatory roles for NF-κB. The International Journal of Biochemistry & Cell Biology 42: 519–523.

    Article  CAS  Google Scholar 

  26. Roman-Blas, J., and S. Jimenez. 2006. NF-κB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis and Cartilage 14: 839–848.

    Article  CAS  PubMed  Google Scholar 

  27. Jeong JW, Lee HH, Choi EO, Lee KW, Kim KY, Kim SG, Hong SH, Kim GY, Park C, Kim HK, et al. 2015. Schisandrae Fructus inhibits IL-1beta-induced matrix metalloproteinases and inflammatory mediators production in SW1353 human chondrocytes by suppressing NF-kappaB and MAPK activation. Drug Development Research 76: 474–483.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wenbo Wang.

Ethics declarations

This experiment was conducted in accordance with the Declaration of Helsinki and Tokyo.

Conflict of Interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, C., Zeng, L., Zhang, T. et al. Tenuigenin Prevents IL-1β-induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing PI3K/AKT/NF-κB Signaling Pathway. Inflammation 39, 807–812 (2016). https://doi.org/10.1007/s10753-016-0309-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-016-0309-3

KEY WORDS

Navigation