아나필락시스 반응과 비만세포 활성화에 대한 한국전통약제의 억제효과

Inhibitory Effects of Several Korean Traditional Herbs on Anaphylactic Reaction and Mast Cell Activation

  • 채옥희 (전북대학교 의학전문대학원 해부학교실, 전북대학교 의과학연구소)
  • Chai, Ok-Hee (Department of Anatomy, Chonbuk National University Medical School and Institute for Medical Sciences, Chonbuk National University)
  • 투고 : 2010.10.08
  • 심사 : 2010.11.04
  • 발행 : 2010.12.31

초록

한방에서 사용되는 약재 중 가자와 지모, 단삼은 면역조절 및 항암효과, 항염증효과가 있다고 알려졌다. 그러나 비만세포와 관련된 아나필락스를 이해할 수 있는 세포학적 기전에 대한 가자와 지모, 단삼의 효과에 대해서는 알려진 바 없다. 본 연구에서는 가자와 지모, 단삼의 메탄올 추출물이 아나필락시스 반응에 대해 어떠한 영향을 끼치는지를 조사하였다. 시험관내 실험과 생체 실험을 통하여, 가자와 지모, 단삼의 메탄올 추출물이 compound 48/80에 의한 아나필락시스와 비만세포 활성화 및 IgE에 의한 피부반응을 관찰하였다. 실험결과는 다음과 같다. 1) 가자와 지모, 단삼의 메탄올 추출물은 compound 48/80에 의한 전신성 아나필락시스와 귀부종 반응, IgE에 의한 피부반응을 억제하였다. 2) Compound 48/80에 의한 비만세포 탈과립과 흰쥐 복강 비만세포로부터 히스타민 유리가 가자와 지모, 단삼의 메탄올 추출물 전처리에 의해 억제되었다. 3) Compound 48/80에 의한 흰쥐 복강 비만세포내로의 칼슘 유입이 가자와 지모, 단삼의 메탄올 추출물 전처리에 의해 현저하게 억제되었다. 이상의 결과로 가자와 지모, 단삼의 메탄올 추출물은 비만세포 탈과립과 비만세포로부터 히스타민 유리, 비만세포내로 칼슘유입을 억제함으로써 compound 48/80에 의한 아나필락시스와 IgE에 의한 피부반응을 억제한다는 것을 알 수 있었다. 이로써 가자와 지모, 단삼은 알레르기 질환에 대한 효과적인 치료제로 이용될 수 있을 것으로 생각된다.

Korean traditional herbs, especially Anemarrhena asphodeloides (A. asphodeloides), Salvia miltiorrhiza (S. miltiorrhiza), and Terminalia chebula (T. chebula) have been known to have the immunomodulatory, anti-tumor, and anti-inflammatory effects. However, direct cellular mechanism underlying the mast cell-mediated anaphylaxis-like reaction has poorly been understood. In the present study, the effects of the methanol extracts of A. asphodeloides (MEAA), S. miltiorrhiza (MESM), and T. chebula (METC) on anaphylactic reaction were investigated. Using in vitro and in vivo experiments, the influences of MEAA, MESM, and METC on the compound 48/80-induced anaphylaxis-like reaction and mast cell activation, and IgEmediated PCA were examined. Results are below; 1) MEAA, MESM, and METC significantly inhibited systemic anaphylaxis-like reaction, ear swelling response, and IgE-mediated PCA. 2) the compound 48/80-induced mast cell degranulation, histamine release of rat peritoneal mast cells (RPMC) were significantly inhibited by the pretreatment with MEAA, MESM, and METC, and 3) the compound 48/80-induced calcium influx in RPMC was significantly inhibited by the pretreatment with MEAA, MESM, and METC. These results suggest that MEAA, MESM, and METC may be an activity to inhibit the compound 48/80-induced or anti-DNP IgE-mediated anaphylactic reactions by blocking histamine release and calcium uptake into RPMC. MEAA, MESM, and METC potentially may serve as an effective therapeutic tool for allergic diseases.

키워드

참고문헌

  1. Bradding P: Novel approaches to the inhibition of mast cells in allergic disease. Clin Exp Allergy 38 : 704-708, 2008. https://doi.org/10.1111/j.1365-2222.2008.02962.x
  2. Chai OH, Lee MS, Han EH, Kim HT, Song CH: Inhibitory effects of Morus alba on compound 48/80-induced anaphylactic reactions and anti-chicken gamma globulin IgE-mediated mast cell activation. Biol Pharm Bull 28 : 1852-1858, 2005. https://doi.org/10.1248/bpb.28.1852
  3. Chang JS, Chiang LC, Chen CC, Liu LT, Wang KC, Lin CC: Antileukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb. Am J Chin Med 29 : 303-312, 2001. https://doi.org/10.1142/S0192415X01000320
  4. Chiang LC, Chang JS, Chen CC, Ng LT, Lin CC: Anti-Herpes simplex virus activity of Bidens pilosa and Houttuynia cordata. Am J Chin Med 31 : 355-362, 2003. https://doi.org/10.1142/S0192415X03001090
  5. Choi YH, Yan GH, Chai OH, Choi YH, Zhang X, Lim JM, Kim JH, Choi SH, Lee MS, Han EH, Kim HT, Song CH: Inhibitory effects of Agaricus blzei on mast cell-mediated anaphylaxis-like reaction. Biol Pharm Bull 29 : 1366-1371, 2006a. https://doi.org/10.1248/bpb.29.1366
  6. Choi YH, Yan GH, Chai OH, Lim JM, Sung SY, Zhang X, Kim JH, Choi SH, Lee MS, Han EH, Kim HT, Song CH: Inhibitory effects of anaphylaxis-like reaction and mast cell activation by water extract from the fruiting body of Phellinus linteus. Biol Pharm Bull 29 : 1360-1365, 2006b. https://doi.org/10.1248/bpb.29.1360
  7. D'Souza P, Amit A, Saxena VS, Bagchi M, Stohs SJ: Antioxidant properties of Aller-7, a novel polyherbal formulation for allergic rhinitis. Drugs Exp Clin Res 30 : 99-109, 2004.
  8. Fang ZY, Lin R, Yuan BX, Yang GD, Liu Y, Zhang H: Tanshinone IIA down-regulates the CD40 expression and decreases MMP-2 activity on atherosclerosis induced by high fatty diet in rabbit. J Ethnopharmacol 115 : 217-222, 2008. https://doi.org/10.1016/j.jep.2007.09.025
  9. Hachisuka H, Nomura H, Sakamoto F, Mori O, Okubo K, Sasai Y: Effect of antianaphylactic agents on substance P induced histamine release from rat peritoneal mast cells. Arch Dermatol Res 280 : 158-162, 1988. https://doi.org/10.1007/BF00456847
  10. Inagaki N, Goto S, Nagai H, Koda A: Homologous passive cutaneous anaphylaxis in various strains of mice. Int Arch Allergy Appl Immunol 81 : 58-61, 1986a. https://doi.org/10.1159/000234108
  11. Inagaki N, Goto S, Yamasaki M, Nagai H, Koda A: Studies on vascular permeability increasing factors involved in 48-hour homologous PCA in the mouse ear. Int Arch Allergy Appl Immunol 80 : 285-290, 1986b. https://doi.org/10.1159/000234067
  12. Jang SI, Kim HJ, Kim YJ, Jeong SI, You YO: Tanshinone IIA inhibits LPS-induced NF-kappa B activation in RAW 264.7 cells: possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways. Eur J Pharmacol 542 : 1-7, 2006. https://doi.org/10.1016/j.ejphar.2006.04.044
  13. Jeong HJ, Koo HN, Na HJ, Kim MS, Hong SH, Em JW, Kim KS, Shin TY, Kim HM: Inhibition of TNF-alpha and IL-6 production by Aucubin through blockade of NF-kappa B activation RBL- 2H3 mast cells. Cytokine 18 : 252-259, 2002. https://doi.org/10.1006/cyto.2002.0894
  14. Klemm S, Ruland J: Inflammatory signal transduction from the $Fc{\varepsilon}RI$ to NF-$\kappa$B. Immunol 211 : 815-820, 2006.
  15. Lantz CS, Boesiger J, Song CH, Mach N, Kobayashi T, Mulligan RC, Nawa Y, Dranoff G, Galli SJ: Role for interleukin-3 in mastcell and basophil development and in immunity to parasites. Nature 392 : 90-93, 1998. https://doi.org/10.1038/32190
  16. Lee B, Trinh HT, Bae EA, Jung K, Kim DH: Mangiferin inhibits passive cutaneous anaphylaxis reaction and pruritus in mice. Planta Med 75 : 1415-1417, 2009. https://doi.org/10.1055/s-0029-1185773
  17. Lee B, Trinh HT, Jung K, Han SJ, Kim DH: Inhibitory effects of steroidal timosaponins isolated from the rhizomes of Anemarrhena asphodeloides against passive cutaneous anaphylaxis reaction and pruritus. Immunopharmacol Immunotoxicol 32 : 357-363, 2010. https://doi.org/10.3109/08923970903383889
  18. Li C, Zhao Y, An H: Observations of the curative effect with various liquid for post operative irrigation of ESS of treating chronic sinusitis and nasal polyps. Lin Chuang Er Bi Yan Hou Ke Za Zhi 15 : 53-54, 2001.
  19. Li GZ, Chai OH, Lee MS, Han EH, Kim HT, Song CH: Inhibitory effects of Houttuynia cordata water extracts on anaphylactic reaction and mast cell activation. Biol Pharm Bull 28 : 1864-1868, 2005a. https://doi.org/10.1248/bpb.28.1864
  20. Li GZ, Chai OH, Song CH: Inhibitory effects of epigallocatechin gallate on compound 48/80-induced mast cell activation and passive cutaneous anaphylaxis. Exp Mol Med 37 : 290-296, 2005b. https://doi.org/10.1038/emm.2005.39
  21. Lorenz D, Wiesner B, Zipper J, Winkler A, Krause E, Beyermann M, Lindau M, Bienert M: Mechanism of peptide-induced mast cell degranulation. Translocation and patch-clamp studies. J Gen Physiol 112 : 577-591, 1998. https://doi.org/10.1085/jgp.112.5.577
  22. Mahesh R, Bhuvana B, Begum VM: Effect of Terminalia chebula aqueous extract on oxidative stress and antioxidant status in the liver and kidney of young and aged rats. Cell Biochem Funct 27 : 358-363, 2009. https://doi.org/10.1002/cbf.1581
  23. Mascotti K, McCullough J, Burger SR: HPC viability measurement: trypan blue versus acridine orange and propidium iodide. Transfusion 40 : 693-696, 2000. https://doi.org/10.1046/j.1537-2995.2000.40060693.x
  24. Mekori YA, Metcalfe DD: Mast cells in innate immunity. Immunol Rev 173 : 131-140, 2000. https://doi.org/10.1034/j.1600-065X.2000.917305.x
  25. Na YC, Chai OH, Song CH: Study of cutaneous neuropeptidesinduced mast cell activation. Kor J Anat 42 : 197-207, 2009. (Korean)
  26. Pratibha N, Saxena VS, Amit A, D'Souza P, Bagchi M, Bagchi D: Anti-inflammatory activities of Aller-7, a novel polyherbal formulation for allergic rhinitis. Int J Tissue React 26 : 43-51, 2004.
  27. Puxeddu I, Ribatti D, Crivellato E, Levi-Schaffer F: Mast cells and eosinophils: A novel link between inflammation and angiogenesis in allergic diseases. J Allergy Clin Immunol 116 : 531-536, 2005. https://doi.org/10.1016/j.jaci.2005.06.007
  28. Suguna L, Singh S, Sivakumar P, Sampath P, Chandrakasan G: Influence of Terminalia chebula on dermal wound healing in rats. Phytother Res 16 : 227-231, 2002. https://doi.org/10.1002/ptr.827
  29. Tanaka S, Mikura S, Hashimoto E, Sugimoto Y, Ichikowa A: $Ca^{2+}$ influx-mediated histamine synthesis and IL-6 release in mast cells activated by monomeric IgE. Eur J Immunol 35 : 460-468, 2005. https://doi.org/10.1002/eji.200425622
  30. Trinh HT, Chae SJ, Joh EH, Son KH, Jeon SJ, Kim DH: Tanshinones isolated from the rhizome of Salvia miltiorrhiza inhibit passive cutaneous anaphylaxis reaction in mice. J Ethnopharmacol 132 : 344-348, 2010. https://doi.org/10.1016/j.jep.2010.07.037
  31. Yeum HS, Lee YC, Kim SH, Roh SS, Lee JC, Seo YB: Fritillaria cirrhosa, Anemarrhena asphodeloids, Lee-Mo-Tang and cyclosporine a inhibit ovalbumin-induced eosinophil accumulation and Th2-mediated bronchial hyperresponsiveness in a murine model of asthma. Basic Clin Pharmacol 100 : 205-213, 2007. https://doi.org/10.1111/j.1742-7843.2007.00043.x
  32. Yoshimura T, Hamaguchi E, Usami E, Nakashima K, Kawaguchi M, Suzuki N, Okamoto Y, Nakao T, Yamazaki F: Increased in vitro release of interferon-gamma from ampicillin-stimulated peripheral blood mononuclear cells in Stevens-Johnson syndrome. Biol Pharm Bull 27 : 929-931, 2004. https://doi.org/10.1248/bpb.27.929