Skip to main content

Advertisement

SpringerLink
Log in

Schisantherin A Exhibits Anti-inflammatory Properties by Down-Regulating NF-κB and MAPK Signaling Pathways in Lipopolysaccharide-Treated RAW 264.7 Cells

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Schisantherin A, a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent under the name of Wuweizi in Chinese traditional medicine. In the present study, we carry out a screening program to identify the anti-inflammatory potentials of schisantherin A. We found that schisantherin A reduced lipopolysaccharide (LPS (1 mg/L))-induced levels of TNF-α, IL-6, NO, and PGE2 (p < 0.01 or p < 0.05), and also reduced levels of iNOS and COX-2 in RAW 264.7 macrophages in a concentration-dependent manner. We further investigated signal transduction mechanisms to determine how schisantherin A affects. RAW264.7 cells were pretreated with 0.5, 2.5, or 25 mg/L of schisantherin A 1 h prior to treatment with 1 mg/L of LPS. Thirty minutes later, cells were harvested and mitogen activated protein kinases (MAPKs) activation and IκBα was measured by Western blot. Alternatively, cells were fixed and nuclear factor-κB (NF-κB) activation was measured using immunocytochemical analysis. Signal transduction studies showed that schisantherin A significantly inhibited extracellular signal-regulated kinase (ERK), p38, and c-jun NH2-terminal kinase (JNK) phosphorylation protein expression. Schisantherin A also inhibited p65-NF-κB translocation into the nucleus by IκBα degradation. By using specific inhibitors of ERK, JNK and p38, we found that schisantherin A may inhibit TNF-α mostly through ERK pathway. Therefore, schisantherin A may inhibit LPS-induced production of inflammatory cytokines by blocking NF-κB and MAPKs signaling in RAW264.7 cells.

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Kubes, P., and D.M. Mccafferty. 2000. Nitric oxide and intestinal inflammation. American Journal of Medicine 109: 150–158.

    Article  CAS  PubMed  Google Scholar 

  2. Guha, M., and N. Mackman. 2001. LPS induction of gene expression in human monocytes. Cellular Signal 13: 85–94.

    Article  CAS  Google Scholar 

  3. Vane, J.R., J.A. Mitchell, I. Appleton, A. Tomlinson, et al. 1994. Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation. PNAS 91: 2046–2050.

    Article  CAS  PubMed  Google Scholar 

  4. Chi, Y.S., H. Lim, H. Park, and H.P. Kim. 2003. Effects of wogonin, a plant flavone from Scutellaria radix, on skin inflammation: in vivo regulation of inflammation-associated gene expression. Biochemical Pharmacology 66: 1271–1278.

    Article  CAS  PubMed  Google Scholar 

  5. Barak, V., I. Kalickman, T. Halperin, S. Birkenfeld, and I. Ginsburg. 2004. PADMA-28, a Tibetan herbal preparation is an inhibitor of inflammatory cytokine production. European Cytokine Network 15: 203–209.

    CAS  PubMed  Google Scholar 

  6. Genovese, M.C. 2005. Biologic therapies in clinical development for the treatment of rheumatoid arthritis. Journal of Clinical Rheumatology 11: S45–S54.

    Article  PubMed  Google Scholar 

  7. Li, R.T., W.S. Xiang, H. Li, Z.W. Lin, and H.D. Sun. 2004. Lancifodilactones B-E, new nortriterpenes from Schisandra lancifolia. Journal of Natural Products 67: 94–97.

    Article  CAS  PubMed  Google Scholar 

  8. Pu, J.X., W.L. Xiao, Y. Lu, R.T. Li, H.M. Li, L. Zhang, S.X. Huang, X. Li, Q.S. Zhao, Q.T. Zheng, and H.D. Sun. 2005. Kadlongilactones A and B, two novel triterpene dilactones from Kadsura longipedunculata possessing a unique skeleton. Organic Letters 7: 5079–5081.

    Article  CAS  PubMed  Google Scholar 

  9. Xiao, W.L., L.M. Yang, N.B. Gong, L. Wu, R.R. Wang, J.X. Pu, X.L. Li, S.X. Huang, Y.T. Zheng, R.T. Li, Y. Lu, and Q.T. Zheng. 2006. Rubriflordilactones A and B, two novel bisnortriterpenoids from Schisandra rubriflora and their biological activities. Organic Letters 8: 991–993.

    Article  CAS  PubMed  Google Scholar 

  10. Chen, Y.G., Y.Y. Xie, K.F. Cheng, K.K. Cheung, and G.W. Qin. 2001. Compounds from Kadsura ananosma. Phytochemistry 58: 1277–1280.

    Article  CAS  PubMed  Google Scholar 

  11. Opletal, L., H. Sovova, and M. Bartlova. 2004. Dibenzocyclooctadiene lignans of the genus Schisandra: importance, isolation and determination. Journal of Chromatography B 812: 357–361.

    CAS  Google Scholar 

  12. Ding, P.L., D.F. Chen, K.F. Bastow, et al. 2004. Cytotoxic isoprenylated flavonoids from the roots of sophora flavescens. Helvetica Chimica Acta 87: 2574–2580.

    Article  CAS  Google Scholar 

  13. Kiso, Y., M. Tohkin, H. Hikino, Y. Ikeya, and H. Taguchi. 1985. Schisandra chinensis (Turcz.) Baill. Planta Medica 4: 331–334.

    Article  PubMed  Google Scholar 

  14. Guo, L.Y., T.M. Hung, K.H. Bae, et al. 2008. Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill. European Journal of Pharmacology 591: 293–299.

    Article  CAS  PubMed  Google Scholar 

  15. Johnson, G.L., and R. Lapadat. 2002. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298: 1911–1912.

    Article  CAS  PubMed  Google Scholar 

  16. Kim, Y.H., S.H. Lee, J.Y. Lee, S.W. Choi, J.W. Park, and T.K. Kwon. 2004. Triptolideinhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase. European Journal of Pharmacology 494: 1–9.

    Article  CAS  PubMed  Google Scholar 

  17. Olsson, S., and R. Sundler. 2006. The role of lipid rafts in LPS-induced signaling in a macrophage cell line. Molecular Immunology 43: 607–612.

    Article  CAS  PubMed  Google Scholar 

  18. Li, Q., and I.M. Verma. 2002. NF-kappaB regulation in the immune system. Nature Reviews. Immunology 2: 725–734.

    Article  CAS  PubMed  Google Scholar 

  19. Bayon, Y., M.A. Ortiz, F.J. Lopez-Hernandez, F. Gao, M. Karin, M. Pfahl, and F.J. Piedrafita. 2003. Inhibition of IkappaB kinase by a new class of retinoid-related anticancer agents that induce apoptosis. Molecular and Cellular Biology 23: 1061–1074.

    Article  CAS  PubMed  Google Scholar 

  20. Takeda, K., T. Kaisho, and S. Akira. 2003. Toll-like receptors. Annual Review of Immunology 21: 335–376.

    Article  CAS  PubMed  Google Scholar 

  21. Towbin, H., T. Staehelin, and J. Gordon. 1992. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Biotechnology 24: 145–149.

    CAS  PubMed  Google Scholar 

  22. Aggarwal, B.B., and K. Natarajan. 1996. Tumor necrosis factors: developments during the last decade. European Cytokine Network 7: 93–124.

    CAS  PubMed  Google Scholar 

  23. Kim, S.J., H.J. Jeong, P.D. Moon, K.M. Lee, H.B. Lee, H.J. Jung, and S.K. Jung. 2005. Anti-inflammatory activity of gumiganghwaltang through the inhibition of nuclear factor-kappa B activation in peritoneal macrophages. Biological and Pharmaceutical Bulletin 28: 233–237.

    Article  CAS  PubMed  Google Scholar 

  24. Martel, P.J., J.P. Pelletier, and H.S. Fahmi. 2003. Arthritis and Rheumatism 33: 155–167.

    Article  Google Scholar 

  25. Huyke, C., K. Engel, K.W. Quirin, et al. 2007. Composition and biological activity of different extracts from Schisandra sphenanthera and Schisandra chinensis. Planta Medica 73: 1116–1126.

    Article  CAS  PubMed  Google Scholar 

  26. Sun, Y., Y.H. Li, Q. Xu, et al. 2006. Ethanol extract from Artemisia vestita, a traditional Tibetan medicine, exerts anti-sepsis action through down-regulating the MAPK and NF-κB pathways. International Journal of Molecular Medicine 17: 957–962.

    PubMed  Google Scholar 

  27. Vandenberghe, W., S. Plaisance, E. Boone, K. Debosscher, M.L. Schmitz, W. Fiers, and G.J. Haegeman. 1998. Biological Chemistry 273: 3285–3290.

    Article  CAS  Google Scholar 

  28. Hommes, D.W., and M.P. Peppelenbosch. 2003. Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut 52: 144–151.

    Article  CAS  PubMed  Google Scholar 

  29. Anderson, K., and R. Sundler. 2000. Signaling to translational activation of tumour necrosis factor-α expression in human THP-1 cells. Cytokine 12: 1784–1787.

    Article  Google Scholar 

  30. Chen, T.H., Y.C. Kao, B.C. Chen, C.H. Chen, P. Chan, and H.M. Lee. 2006. Dipyridamole activation of mitogen-activated protein kinase phosphatase-1 mediates inhibition of lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells. European Journal of Pharmacology 541: 138–146.

    Article  CAS  PubMed  Google Scholar 

  31. Kim, B.C., J.W. Choi, H.Y. Hong, S.A. Lee, S. Hong, E.H. Park, S.J. Kim, and C.J. Lim. 2006. Heme oxygenase-1 mediates the anti-inflammatory effect of mushroom Phellinus linteus in LPS-stimulated RAW264.7 macrophages. Journal of Ethnopharmacology 106: 364–371.

    Article  PubMed  Google Scholar 

  32. Hyo, W.J., H.K. Young, C.B. Yong, and M.P. Kwon. 2007. Wen-Pi-Tang-Hab- Wu-Ling- San extract inhibits the release of inflammatory mediators from LPS-stimulated mouse macrophages. Journal of Ethnopharmacology 114: 439–445.

    Article  Google Scholar 

  33. Baeuerle, P.A., and D. Baltimore. 1996. NF-kappa B: ten years after. Cell 87: 13–20.

    Article  CAS  PubMed  Google Scholar 

  34. Kim, J.B., A.R. Han, E.Y. Park, et al. 2007. Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by Poncirin through the NF-κB inactivation in RAW 264.7 macrophage cells. Biological & Pharmaceutical Bulletin 30: 2345–2351.

    Article  CAS  Google Scholar 

  35. Cohen, J. 2002. The immunopathogenesis of sepsis. Nature 420: 885–891.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (No. 30671586).

Author information

Authors and Affiliations

  1. Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, People’s Republic of China

    Xinxin Ci, Kan Xu, Hongyu Li, Yu Song, Dacheng Wang & Xuming Deng

  2. The College of Life Sciences and Technology, Kunming University of Science and Technology, 253 Xuehu Road, Kunming, 650093, China

    Rong Ren & Rongtao Li

  3. Jilin Provincial Center for Animal Disease Control and Prevention, 311 Liao’yang street, Changchun, 130062, China

    Qinlei Yu

Authors
  1. Xinxin Ci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rong Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kan Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongyu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qinlei Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dacheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rongtao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Xuming Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xuming Deng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ci, X., Ren, R., Xu, K. et al. Schisantherin A Exhibits Anti-inflammatory Properties by Down-Regulating NF-κB and MAPK Signaling Pathways in Lipopolysaccharide-Treated RAW 264.7 Cells. Inflammation 33, 126–136 (2010). https://doi.org/10.1007/s10753-009-9166-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-009-9166-7

KEY WORDS

Search

Navigation