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Anti-inflammatory effects of Dendrobium nobile derived phenanthrenes in LPS-stimulated murine macrophages

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Abstract

Dendrobium nobile belongs to the Orchidaceae family and is one of the medicinal herbs used in traditional Chinese medicine as a therapeutic agent for gastrointestinal and cardiovascular diseases. In this study, we separated three phenanthrenes (ephemeranthol A (EA), 1,5,7-trimethoxyphenanthren-2-ol (TP), dehydroorchinol (DO)) from D. nobile, and compared their anti-inflammatory activities. TP is a new phenanthrene compound and its structure was determined from 1H, 13C NMR and HR-ESI-MS data. To analyze the anti-inflammatory activities of the phenanthrenes, Raw 264.7 cells were used, since they are immature-macrophages and easily matured by LPS stimulation. EA and DO showed anti-inflammatory activities in the activated Raw 264.7 cells. That is, we showed that EA is a potent inhibitor of the production of nitric oxide and pro-inflammatory cytokines. The inhibitory activities of phenanthrenes were found to be caused by blockage of NF-κB activation and the phosphorylation of MAP kinases in the macrophages. These results are expected to serve as a guide for future studies on the ability of phenanthrenes to inhibit acute and chronic inflammatory diseases.

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References

  • Arend, W.P., and J.M. Dayer. 1995. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis and Rheumatism 38: 151–160.

    Article  CAS  PubMed  Google Scholar 

  • Barnes, P.J., and M. Karin. 1997. Nuclear factor-kappaB: A pivotal transcription factor in chronic inflammatory diseases. New England Journal of Medicine 336: 1066–1071.

    Article  CAS  PubMed  Google Scholar 

  • Beutler, B., and A. Cerami. 1989. The biology of cachectin/TNF: A primary mediator of the host response. Annual Review of Immunology 7: 625–655.

    Article  CAS  PubMed  Google Scholar 

  • Bian, Z.M., S.G. Elner, A. Yoshida, and V.M. Elner. 2003. Human RPE-monocyte co-culture induces chemokine gene expression through activation of MAPK and NIK cascade. Experimental Eye Research 76: 573–583.

    Article  CAS  PubMed  Google Scholar 

  • Brennan, F.M., R.N. Maini, and M. Feldmann. 1998. Role of pro-inflammatory cytokines in rheumatoid arthritis. Springer Seminars in Immunopathology 20: 133–147.

    Article  CAS  PubMed  Google Scholar 

  • Broering, T.J., and G.R. Morrow. 1999. Oxygenated dihydorphenanthrenes via quinol acetals: A brief synthesis of orchinol. Synthetic Communications 29: 1135–1142.

    Article  CAS  Google Scholar 

  • Dawid-Pać, R. 2013. Medicinal plants used in treatment of inflammatory skin diseases. Postȩpy Dermatologii i Alergologii 30: 170–177.

    PubMed Central  PubMed  Google Scholar 

  • Dinarello, C.A. 1996. Biologic basis for interleukin-1 in disease. Blood 87: 2095–2147.

    CAS  PubMed  Google Scholar 

  • Ding, W., J. Gu, L. Cao, N. Li, G. Ding, Z. Wang, L. Chen, X. Xu, and W.J. Xiao. 2014. Traditional Chinese herbs as chemical resource library for drug discovery of anti-infective and anti-inflammatory. Journal of Ethnopharmacology 155: 589–598.

    Article  CAS  PubMed  Google Scholar 

  • Duval, D.L., D.R. Miller, J. Collier, and R.E. Billings. 1996. Characterization of hepatic nitric oxide synthase: Identification as the cytokine-inducible form primarily regulated by oxidants. Molecular Pharmacology 50: 277–284.

    CAS  PubMed  Google Scholar 

  • Fan, C., W. Wang, Y. Wang, G. Qin, and W. Zhao. 2001. Chemical constituents from Dendrobium densiflorum. Phytochemistry 57: 1255–1258.

    Article  CAS  PubMed  Google Scholar 

  • Feldmann, M., F.M. Brennan, and R.N. Maini. 1996. Role of cytokines in rheumatoid arthritis. Annual Review of Immunology 14: 397–440.

    Article  CAS  PubMed  Google Scholar 

  • Green, S.J., L.F. Scheller, M.A. Marletta, M.C. Seguin, F.W. Klotz, M. Slayter, B.J. Nelson, and C.A. Nacy. 1994. Nitric oxide: Cytokine-regulation of nitric oxide in host resistance to intracellular pathogens. Immunology Letters 43: 87–94.

    Article  CAS  PubMed  Google Scholar 

  • Honda, C., and M. Yamaki. 2000. Phenanthrenes from Dendrobium plicatile. Phytochemistry 53: 987–990.

    Article  CAS  PubMed  Google Scholar 

  • Hsieh, Y.S., C. Chien, S.K. Liao, S.F. Liao, W.T. Hung, W.B. Yang, C.C. Lin, T.J. Cheng, C.C. Chang, J.M. Fang, and C.H. Wong. 2008. Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense. Bioorganic & Medicinal Chemistry 16: 6054–6068.

    Article  CAS  Google Scholar 

  • Hu, J.M., J.J. Chen, H. Yu, Y.X. Zhao, and J. Zhou. 2008. Five new compounds from Dendrobium longicornu. Planta Medica 74: 535–539.

    Article  CAS  PubMed  Google Scholar 

  • Huk, I., V. Brovkovych, J. Nanobash Vili, G. Weigel, C. Neumayer, L. Partyka, S. Patton, and T. Malinski. 1998. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischaemia-reperfusion injury: An experimental study. British Journal of Surgery 85: 1080–1085.

    Article  CAS  PubMed  Google Scholar 

  • Hwang, J.S., S.A. Lee, S.S. Hong, X.H. Han, C. Lee, S.J. Kang, D. Lee, Y. Kim, J.T. Hong, M.K. Lee, and B.Y. Hwang. 2010. Phenanthrenes from Dendrobium nobile and their inhibition of the LPS-induced production of nitric oxide in macrophage Raw 264.7 cells. Bioorganic & Medicinal Chemistry Letters 20: 3785–3787.

    Article  CAS  Google Scholar 

  • 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 

  • Kim, S.H., J. Kim, and R.P. Sharma. 2004. Inhibition of p38 and ERK MAP kinases blocks endotoxin-induced nitric oxide production and differentially modulates cytokine expression. Pharmacological Research 49: 433–439.

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto, T., S. Akira, M. Narazaki, and T. Taga. 1995. Interleukin-6 family of cytokines and gp130. Blood 86: 1243–1254.

    CAS  PubMed  Google Scholar 

  • Lawrence, T., D.W. Gilroy, P.R. Colville-Nash, and D.A. Willoughby. 2001. Possible new role for NF-kappaB in the resolution of inflammation. Nature Medicine 7: 1291–1297.

    Article  CAS  PubMed  Google Scholar 

  • Lee, Y.H., J.D. Park, N.I. Baek, S.I. Kim, and B.Z. Ahn. 1995. In vitro and in vivo antitumoral phenanthrenes from the aerial parts of Dendrobium nobile. Planta Medica 61: 178–180.

    Article  CAS  PubMed  Google Scholar 

  • Li, Y., C.L. Wang, Y.J. Wang, S.X. Guo, J.S. Yang, X.M. Chen, and P.G. Xiao. 2009. Three new bibenzyl derivatives from Dendrobium candidum. Chemical & Pharmaceutical Bulletin (Tokyo) 57: 218–219.

    Article  CAS  Google Scholar 

  • Lowenstein, C.J., S.L. Hill, A. Lafond-Walker, J. Wu, G. Allen, M. Landavere, N.R. Rose, and A. Herskowitz. 1996. Nitric oxide inhibits viral replication in murine myocarditis. Journal of Clinical Investigation 97: 1837–1843.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Luo, A., and Y. Fan. 2011. Immune stimulating activity of water-soluble polysaccharide fractions from Dendrobium nobile Lindl. African Journal of Pharmacy and Pharmacology 5: 625–631.

    Article  CAS  Google Scholar 

  • Luo, A., X. He, S. Zhou, Y. Fan, T. He, and Z. Chun. 2009. In vitro antioxidant activities of a water-soluble polysaccharide derived from Dendrobium nobile Lindl. extracts. International Journal of Biological Macromolecules 45: 359–363.

    Article  CAS  PubMed  Google Scholar 

  • Makarov, S.S. 2000. NF-kappaB as a therapeutic target in chronic inflammation: Recent advances. Molecular Medicine Today 6: 441–448.

    Article  CAS  PubMed  Google Scholar 

  • Nagy, G., and A. Perl. 2006. The role of nitric oxide in abnormal T cell signal transduction in systemic lupus erythematosus. Clinical Immunology 118: 145–151.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nickoloff, B.J., Y. Ben-Neriah, and E. Pikarsky. 2005. Inflammation and cancer: Is the link as simple as we think? Journal of Investigative Dermatology 124: x–xiv.

    Article  CAS  PubMed  Google Scholar 

  • O'leary, K. A., De Pascual-Tereasa, S., P.W. Needs, Y.P. Bao, N.M. O’brien, and G. Williamson. 2004. Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mutation Research 551: 245–254.

    Article  PubMed  Google Scholar 

  • Renard, P., and M. Raes. 1999. The proinflammatory transcription factor NFkappaB: A potential target for novel therapeutical strategies. Cell Biology and Toxicology 15: 341–344.

    Article  CAS  PubMed  Google Scholar 

  • Shu, Y., D.M. Zhang, and S.X. Guo. 2004. A new sesquiterpene glycoside from Dendrobium nobile Lindl. Journal of Asian Natural Products Research 6: 311–314.

    Article  CAS  PubMed  Google Scholar 

  • Stichtenoth, D.O., and J.C. Frolich. 1998. Nitric oxide and inflammatory joint diseases. British Journal of Rheumatology 37: 246–257.

    Article  CAS  PubMed  Google Scholar 

  • Tezuka, Y., H. Hirano, T. Kikuchi, and G.-J. Xu. 1991. Constituents of Ephemerantha lonchophylla; isolation and structure elucidation of a new phenolic compounds, ephemeranthol-A, ephemeranthol-B, and ephemeranthoquinone, and of a new diterpene glucoside, ephemeranthoside. Chemical & Pharmaceutical Bulletin (Tokyo) 39: 593–598.

    Article  CAS  Google Scholar 

  • Theuma, P., and V.A. Fonseca. 2003. Inflammation and emerging risk factors in diabetes mellitus and atherosclerosis. Current Diabetes Reports 3: 248–254.

    Article  PubMed  Google Scholar 

  • Weinberg, J.B. 1998. Nitric oxide as an inflammatory mediator in autoimmune MRL-lpr/lpr mice. Environmental Health Perspectives 106: 1131–1137.

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang, H., S.H. Sung, and Y.C. Kim. 2007. Antifibrotic phenanthrenes of Dendrobium nobile stems. Journal of Natural Products 70: 1925–1929.

    Article  CAS  PubMed  Google Scholar 

  • Ye, Q., G. Qin, and W. Zhao. 2002. Immunomodulatory sesquiterpene glycosides from Dendrobium nobile. Phytochemistry 61: 885–890.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, G.N., L.Y. Zhong, S.W. Bligh, Y.L. Guo, C.F. Zhang, M. Zhang, Z.T. Wang, and L.S. Xu. 2005. Bi-bicyclic and bi-tricyclic compounds from Dendrobium thyrsiflorum. Phytochemistry 66: 1113–1120.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, X., J.K. Xu, J. Wang, N.L. Wang, H. Kurihara, S. Kitanaka, and X.S. Yao. 2007. Bioactive bibenzyl derivatives and fluorenones from Dendrobium nobile. Journal of Natural Products 70: 24–28.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, Y., G.L. Mills, and M.G. Nair. 2003. Cyclooxygenase inhibitory and antioxidant compounds from the fruiting body of an edible mushroom, Agrocybe aegerita. Phytomedicine 10: 386–390.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, W., Q. Ye, X. Tan, H. Jiang, X. Li, K. Chen, and A.D. Kinghorn. 2001. Three new sesquiterpene glycosides from Dendrobium nobile with immunomodulatory activity. Journal of Natural Products 64: 1196–1200.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the research Grant of the Chungbuk National University in 2013.

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Correspondence to Chul Young Kim or Jae Kwon Lee.

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Kim, J.H., Oh, SY., Han, SB. et al. Anti-inflammatory effects of Dendrobium nobile derived phenanthrenes in LPS-stimulated murine macrophages. Arch. Pharm. Res. 38, 1117–1126 (2015). https://doi.org/10.1007/s12272-014-0511-5

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