The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology (한방안이비인후피부과학회지)

The Society of Korean Medicine Ophthalmology, Otolaryngology & Dermatology (대한한방안이비인후피부과학회)
권호 표지

The Effect of Silibinin Extracted from Cirsium Japonicum on Allergic Inflammation

대계(大薊)의 주성분인 Silibinin이 알레르기 염증반응에 미치는 효과(效果)

  • 김범락 (경원대학교 한의과대학 안이비인후피부과학 교실) ;
  • 김경준 (경원대학교 한의과대학 안이비인후피부과학 교실)
  • Received : 2010.03.06
  • Accepted : 2010.04.09
  • Published : 2010.04.25
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Abstract

Silibinin is the major active molecule of silymarin, the mixture of flavonolignans extracted from Cirsium japonicum (CJ). It has been used for treatment of hepatitis and inflammation related diseases. The aim of this study was to prove whether Silibinin has effectiveness for allergic inflammation. Silibinin processes the inflammatory reaction in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (PMA plus A23187) stimulated human mast cell line (HMC-1). Its effect was examined by ELISA, RT-PCR, Western blot, and Luciferase assay. The results were Silibinin inhibited the expression of histamine, TNF-$\alpha$ (tumor necrosis factor-$\alpha$), IL-6 (interleukin-6), and IL-8 (interleukin-8). Silibinin suppressed NF-${\kappa}B$ (nuclear factor kappa B) activation in stimulated HMC-1 (human mast cell-1). This effect was mediated through inhibition of phosphorylation and degradation of $IkB{\alpha}$, an inhibitor of NF-kB. Silibinin significantly inhibited induction of NF-kB promoter mediated Luciferase assay. These results suggest that Silibinin has a potential molecule for therapy of mast cell-derived allergic inflammatory diseases.

Keywords

References

  1. 白萬基. 最新耳鼻咽喉科學. 서울. 一潮閣. 1999:192-95.
  2. 大韓耳鼻咽喉科學會 編. 耳鼻咽喉科學. 서울. 一潮閣. 2005:269.
  3. Janeway, C. A. Jr., Travers, P., Walport, M., & Shlomchik, M. 면역생물학 (Immunobiology 6th edition). 김선영 외 14인 역. 서울: 라이프사이언스. 2005:13, 46-7, 78-80, 564-6.
  4. Goldsby, R. A., Kindt, T. J., Osborne, B. A., & Kuby, J. KUBY 면역학 (Kuby immunology). 강호영 외 12인 역. 서울: 월드사이언스. 2006:263, 419-20, 398-423, 417-8, 405.
  5. Thomas, P. S. Tumor necrosis factor-alpha: the role of this multifunctional cytokine in asthma. Immunol Cell Biol. 2001;79(2):132-40. https://doi.org/10.1046/j.1440-1711.2001.00980.x
  6. Naka, S., Suto, H., Kakurai, M., Sedgwick, J. D., Tsai, M., & Galli, S. J. Mast cells enhance T cell activation: importance of mast cell-derived TNF. Proc Natl Acad Sci USA. 2005;10:6467-72.
  7. Bodreau, R. T., Hoskin, D. W., & Lin, T. J. Phosphatase inhibition potentiates IL-6 production by mast cells in response to Fc ${\varepsilon}$RI-mediated activation: involvement of p38 MAPK. J Leukoc Biol. 2004;76(5):1075-81. https://doi.org/10.1189/jlb.1003498
  8. Murayama, T., Mukaida, N., Sadanari, H., Yamaguchi, N., Khabar, K. S., Tanaka, J., Matsushima, K., Mori, S., & Eizuru, Y. The immediate early gene 1 product of human cytomegalovirus is sufficient for up-regulation of interleukin-8 gene expression. Biochem Biophys Res Commun. 2000;279(1):298-304. https://doi.org/10.1006/bbrc.2000.3923
  9. Kuprsh, D. V., Udalova, I. A., Turetskaya, R. L., Rice, N. R., & Nedospasov, S. A. Conserved kappa B element located downstream of the tumor necrosis factor alpha gene: distinct NF-kappa B binding pattern and enhancer activity in LPS activated murine macrophages. Oncogene. 1995;11(1):97-106.
  10. Galien, R., Evans, H. F., & Garcia, T. Involvement of CCAAT/enhancer-binding protein and nuclear factor-kappa B binding site in interleukin-6 promoter inhibition by estrogens. Mol Endocrinol. 1996;10(6):713-22. https://doi.org/10.1210/me.10.6.713
  11. 國家中醫學管理局 編委會. 中華本草. 上海科學技術出版社. 1995:7962-3.
  12. 辛民敎. 原色臨床本草學. 서울:永林出版社. 1988:433-4.
  13. 江蘇新醫學院 編. 中藥大辭典. 서울:成輔社. 1982:115-6.
  14. 李廷周. 大薊약침액이 Reactive oxygen species 소거 활성 및 항산화에 미치는 영향. 동국대학교 대학원. 2006.
  15. Schumann, J., Prockl, J., Kiemer, A. K., Vollmar, A. M., Bang, R., & Tiegs, G. Silibinin protects mice from T cell-dependent liver injury. Journal of hepatology. The journal of the European Association for the Study of the Liver. 2003;39(3):333-40.
  16. Kang, SN., Lee, MH., Kim, KM., Cho, D., & Kim, TS. Induction of human promyelocytic leukemia HL-60 cell differentiation into monocytes by Silibinin : involvement of protein kinase C1. Biochemical Pharmacology. 2001;1(12):1487-95.
  17. Singh, R. P., & Agarwal, R. Mechanisms and preclinical efficacy of sililbinin in preventing skin cancer. European journal of cancer. 2005;41(13):1969-79. https://doi.org/10.1016/j.ejca.2005.03.033
  18. 許浚. 原本東醫寶鑑. 서울:南山堂. 1989:730.
  19. 김호철. 한약약리학. 서울:집문당. 2004:298.
  20. 한국약학대학협의회 약물학분과회. pharmacology (약물학). 서울:도서출판 신일북스. 2007:443.
  21. 김영선. 大薊 LPS로 유도된 Mouse BV2 Microglial cells의 염증반응에 미치는 영향. 원광대학교 대학원. 2008.
  22. 박홍주. 大薊 및 飛廉의 항염활성 비교. 경희대학교 대학원. 2008.
  23. Williams, C. M. M., & Galli, S. J. Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med. 2000;192(3):455-62. https://doi.org/10.1084/jem.192.3.455
  24. Ptak, W., Geba, G. P., & Askenase, P. W. Initiation of delayed-type hypersensitivity by low doses of monoclonal IgE antibody: Mediation by serotonin and inhibition by histamine. J. Immunol. 1991;170:3929-36.
  25. Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., & Li, J., et al. IKK-1 and IKK-2: cytokine-activated I-kappa B kinases essential for NF-kappa B activation. Science. 1997;278:860-6. https://doi.org/10.1126/science.278.5339.860
  26. Regnier, C. H., Song, H. Y., Gao, X., Goeddel, D. V., Cao, Z., & Rothe, M. Identification and characterization of an IKappa kinase. Cell. 1997;90:373-83. https://doi.org/10.1016/S0092-8674(00)80344-X
  27. Zandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M., & Karin, M. The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell. 1997;91:243-52. https://doi.org/10.1016/S0092-8674(00)80406-7
  28. Chen, F. E., Huang, D-B., Chen, Y-Q., & Ghosh, G. Crystal structure of p50/p65 heterodimer of transcription factor NF-${\kappa}$B bound to DNA. Nature. 1998;391:410-3. https://doi.org/10.1038/34956
  29. Beg, A. A., & Baldwin, A. S. Jr. The I kappa B protein: multifunctional regulators of Re 1/NF-kappa B transcription factor. Genes Dev. 1993;7(11):2064-70. https://doi.org/10.1101/gad.7.11.2064
  30. Palombella, V. J., Rando, O. J., Goldberg, A. L., & Maniatis, T. The ubiquitinproteasome pathway is required for processing the NF-${\kappa}$B1 precursor protein and the activation of NF-${\kappa}$B. Cell. 1994;78(5):773-85. https://doi.org/10.1016/S0092-8674(94)90482-0
  31. Baldwin, A. S. Jr. The transcription factor NF-${\kappa}$B and human disease. J Clin Invest. 2000;107:3-6.
  32. Barnes, P. J., & Karin, M. Nuclear factor-kB: a pivotal transcription factor in chronic inflammatory disease. N Engl J Med. 1997;336:1066-71. https://doi.org/10.1056/NEJM199704103361506
  33. Rao, A. NF-ATp : a transcription factor required for the co-ordinate induction of several cytokine genes. Immunol Today. 1994;15(6):274-81. https://doi.org/10.1016/0167-5699(94)90007-8
  34. Fiorini, E., Marchisio, P. C., Scupoli, M. T., Poffe, O., Tagliabue, E., Brentegani, M., Colombatti, M., Santini, F., Tridente, G., & Ramarli, D. Adhesion of immature and mature T cells induces in human thymic epithelial cells (TEC) activation of IL-6 gene transcription factor (NF-kappaB and NF-IL6) and IL-6 gene expression : role of alpha3beta1 and alpha6beta4 integrins. Dev Immunol. 2000;7:195-208. https://doi.org/10.1155/2000/48239