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Cryptotanshinone Suppressed Inflammatory Cytokines Secretion in RAW264.7 Macrophages through Inhibition of the NF-κB and MAPK Signaling Pathways

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Abstract

Cryptotanshinone (CTS), a major constituent extracted from the medicinal herb Salvia miltiorrhiza Bunge, has well-documented antioxidative and anti-inflammatory effects. In the present study, the pharmacological effects and underlying molecular mechanisms of CTS on lipopolysaccharide (LPS)-induced inflammatory responses were investigated. By enzyme-linked immunosorbent assay, we observed that CTS reduced significantly the production of proinflammatory mediators (tumor necrosis factor-α and interleukin-6) induced by LPS in murine macrophage-like RAW264.7 cells. Mechanistically, CTS inhibited markedly the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, p38MAPK, and JNK, which are crucially involved in regulation of proinflammatory mediator secretion. Moreover, immunofluorescence and western blot analysis indicated that CTS abolished completely LPS-triggered nuclear factor-κB (NF-κB) activation. Taken together, these data implied that NF-κB and MAPKs might be the potential molecular targets for clarifying the protective effects of CTS on LPS-induced inflammatory cytokine production in macrophages.

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References

  1. Kim, S.Y., T.C. Moon, H.W. Chang, K.H. Son, S.S. Kang, and H.P. Kim. 2002. Effects of tanshinone I isolated from Salvia miltiorrhiza Bunge on arachidonic acid metabolism and in vivo inflammatory responses. Phytotherapy Research 16: 616–620.

    Article  PubMed  CAS  Google Scholar 

  2. Ng, T.B., F. Liu, and Z.T. Wang. 2000. Antioxidative activity of natural products from plants. Life Sciences 66: 709–723.

    Article  PubMed  CAS  Google Scholar 

  3. Park, E.J., Y.Z. Zhao, Y.C. Kim, and D.H. Sohn. 2007. PF2401-SF, standardized fraction of Salvia miltiorrhiza and its constituents, tanshinone I, tanshinone IIA, and cryptotanshinone, protect primary cultured rat hepatocytes from bile acid-induced apoptosis by inhibiting JNK phosphorylation. Food and Chemical Toxicology 45: 1891–1898.

    Article  PubMed  CAS  Google Scholar 

  4. Zhou, L., Z. Zuo, and M.S. Chow. 2005. Danshen: An overview of its chemistry, pharmacology, pharmacokinetics, and clinical use. Journal of Clinical Pharmacology 45: 1345–1359.

    Article  PubMed  CAS  Google Scholar 

  5. Adams, J.D., R. Wang, J. Yang, and E.J. Lien. 2006. Preclinical and clinical examinations of Salvia miltiorrhiza and its tanshinones in ischemic conditions. Chinese Medicine 1: 3.

    Article  PubMed  Google Scholar 

  6. Jung, H.W., U.K. Seo, J.H. Kim, K.H. Leem, and Y.K. Park. 2009. Flower extract of Panax notoginseng attenuates lipopolysaccharide-induced inflammatory response via blocking of NF-kappaB signaling pathway in murine macrophages. Journal of Ethnopharmacology 122: 313–319.

    Article  PubMed  Google Scholar 

  7. Choi, H.S., D.I. Cho, H.K. Choi, S.Y. Im, S.Y. Ryu, and K.M. Kim. 2004. Molecular mechanisms of inhibitory activities of tanshinones on lipopolysaccharide-induced nitric oxide generation in RAW 264.7 cells. Archives of Pharmacal Research 27: 1233–1237.

    Article  PubMed  CAS  Google Scholar 

  8. van der Bruggen, T., S. Nijenhuis, E. van Raaij, J. Verhoef, and B.S. van Asbeck. 1999. Lipopolysaccharide-induced tumor necrosis factor alpha production by human monocytes involves the raf-1/MEK1-MEK2/ERK1-ERK2 pathway. Infection and Immunity 67: 3824–3829.

    PubMed  Google Scholar 

  9. Andersson, K., and R. Sundler. 2000. Signalling to translational activation of tumour necrosis factor-alpha expression in human THP-1 cells. Cytokine 12: 1784–1787.

    Article  PubMed  CAS  Google Scholar 

  10. Fitzgerald, K.A., D.C. Rowe, and D.T. Golenbock. 2004. Endotoxin recognition and signal transduction by the TLR4/MD2-complex. Microbes and Infection 6: 1361–1367.

    Article  PubMed  CAS  Google Scholar 

  11. Kerfoot, S.M., and P. Kubes. 2005. Local coordination verses systemic disregulation: Complexities in leukocyte recruitment revealed by local and systemic activation of TLR4 in vivo. Journal of Leukocyte Biology 77: 862–867.

    Article  PubMed  CAS  Google Scholar 

  12. Beutler, B. 2000. Tlr4: Central component of the sole mammalian LPS sensor. Current Opinion in Immunology 12: 20–26.

    Article  PubMed  CAS  Google Scholar 

  13. Ghosh, S., M.J. May, and E.B. Kopp. 1998. NF-kappa B and Rel proteins: Evolutionarily conserved mediators of immune responses. Annual Review of Immunology 16: 225–260.

    Article  PubMed  CAS  Google Scholar 

  14. Dobrovolskaia, M.A., and S.N. Vogel. 2002. Toll receptors, CD14, and macrophage activation and deactivation by LPS. Microbes and Infection 4: 903–914.

    Article  PubMed  CAS  Google Scholar 

  15. Jeon, S.J., K.H. Son, Y.S. Kim, Y.H. Choi, and H.P. Kim. 2008. Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots of Salvia miltiorrhiza Bunge. Archives of Pharmacal Research 31: 758–763.

    Article  PubMed  CAS  Google Scholar 

  16. Lee, P., J. Hur, J. Lee, J. Kim, J. Jeong, I. Kang, S.Y. Kim, and H. Kim. 2006. 15, 16-dihydrotanshinone I suppresses the activation of BV-2 cell, a murine microglia cell line, by lipopolysaccharide. Neurochemistry International 48: 60–66.

    Article  PubMed  CAS  Google Scholar 

  17. Jin, D.Z., L.L. Yin, X.Q. Ji, and X.Z. Zhu. 2006. Cryptotanshinone inhibits cyclooxygenase-2 enzyme activity but not its expression. European Journal of Pharmacology 549: 166–172.

    Article  PubMed  CAS  Google Scholar 

  18. Baldwin, A.S., Jr. 1996. The NF-kappa B and I kappa B proteins: New discoveries and insights. Annual Review of Immunology 14: 649–683.

    Article  PubMed  CAS  Google Scholar 

  19. Suh, S.J., U.H. Jin, H.J. Choi, H.W. Chang, J.K. Son, S.H. Lee, S.J. Jeon, K.H. Son, Y.C. Chang, Y.C. Lee, and C.H. Kim. 2006. Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-alpha-induced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-kappaB and AP-1. Biochemical Pharmacology 72: 1680–1689.

    Article  PubMed  CAS  Google Scholar 

  20. Cao, W., C. Bao, E. Padalko, and C.J. Lowenstein. 2008. Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling. The Journal of Experimental Medicine 205: 1491–1503.

    Article  PubMed  CAS  Google Scholar 

  21. Wu, M.J., L. Wang, H.Y. Ding, C.Y. Weng, and J.H. Yen. 2004. Glossogyne tenuifolia acts to inhibit inflammatory mediator production in a macrophage cell line by downregulating LPS-induced NF-kappa B. Journal of Biomedical Science 11: 186–199.

    PubMed  CAS  Google Scholar 

  22. Cheng, Y.W., C.Y. Chang, K.L. Lin, C.M. Hu, C.H. Lin, and J.J. Kang. 2008. Shikonin derivatives inhibited LPS-induced iNOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling. Journal of Ethnopharmacology 120: 264–271.

    Article  PubMed  CAS  Google Scholar 

  23. Chen, C.C., P.C. Tsai, B.L. Wei, and W.F. Chiou. 2008. 8-Prenylkaempferol suppresses inducible nitric oxide synthase expression through interfering with JNK-mediated AP-1 pathway in murine macrophages. European Journal of Pharmacology 590: 430–436.

    Article  PubMed  CAS  Google Scholar 

  24. Jung, H.W., C.H. Yoon, Y.H. Kim, Y.C. Boo, K.M. Park, and Y.K. Park. 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  PubMed  Google Scholar 

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Acknowledgments

This study was supported by research grants from National Natural Science Foundation of China (no. 30811120434, no. 30772576), the National Science and Technology Major Project of China “Key New Drug Creation and Manufacturing Program” [Grant 2009ZX09102-152, 2009ZX09303-007], Major Program in Key Field of People's Government of Guangdong Province (P. R. of China, no. 2003A30904), and the Key Natural Science Foundation of Guangdong Province, People's Republic of China (no. 7117380).

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  1. Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Wai Huan Dong Road 132, Higher Education Mega Center, Guangzhou, 510006, People’s Republic of China

    Shu Tang, Xiao-Yan Shen, He-Qing Huang, Suo-Wen Xu, Yang Yu, Chang-Hua Zhou, Shao-Rui Chen, Kang Le, Yu-Hua Wang & Pei-Qing Liu

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  1. Shu Tang
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Correspondence to Pei-Qing Liu.

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Tang, S., Shen, XY., Huang, HQ. et al. Cryptotanshinone Suppressed Inflammatory Cytokines Secretion in RAW264.7 Macrophages through Inhibition of the NF-κB and MAPK Signaling Pathways. Inflammation 34, 111–118 (2011). https://doi.org/10.1007/s10753-010-9214-3

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