Effects of Danggwisayeokgaohsuyusaenggang-tang(當歸四逆加吳茱萸生薑湯) on Collagen-induced Arthritis in Mice

Collagen으로 유발된 생쥐의 관절염에 대한 당귀사역가오수유생강탕(當歸四逆加吳茱萸生薑湯)의 효과

  • Kim, Min-Kyun (Dept. of Rehabilitation Medicine, College of Oriental Medicine, Dae-Jeon University) ;
  • Oh, Min-Seok (Dept. of Rehabilitation Medicine, College of Oriental Medicine, Dae-Jeon University)
  • 김민균 (대전대학교 한의과대학 한방재활의학과교실) ;
  • 오민석 (대전대학교 한의과대학 한방재활의학과교실)
  • Received : 2011.03.15
  • Accepted : 2011.04.07
  • Published : 2011.04.30

Abstract

Objectives : This study was carried out to know the effects of Danggwisayeokgaohsuyusaenggang-tang(hereinafter referred to DST) on arthritis induced by collagen on DBA/1 OlaHsd mice. Methods : For this purpose, DST was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, high performance liquid chromatograph(HPLC) analysis, arthritis index, value of immunocyte in draining lymph node and paw joint, cytokine were measured in vivo. Results : 1. The cytotoxicity against human fibroblast cells(hFCs) was not measured in any concentration. 2. In HPLC analysis, There are high peak patterns at 8 minute(min), 12 min, 35 min, 45 min. 3. The arthritis index was decreased significantly. 4. The degree of arthritis induced damage of joint of DST group is slight compared with control group in histopathologic observation(Hematoxylin and eosin stain(H&E), Masson's trichrome(M-T) staining). 5. In total cell counts of draining lymph node(DLN) and paw joint, the cells in DLN decreased significantly on DST 200 mg/kg and the cells in paw joint decreased significantly on 200 mg/kg and 50 mg/kg. 6. In DLN, $CD4^+/CD25^+$, $CD3^+/CD69^+$, major histocompatibility complex(MHC), class-II/$CD11c^+$ cells decreased significantly on DST 200 mg/kg and 50 mg/kg $CD3^+/CD8^+$ cells decreased significantly on DST 200 200 mg/kg, $CD4^+$, $CD3^+/CD44^+$ cells decreased. 7. In paw joints, $CD4^+$, $CD11b^+/Gr-1^+$ cells decreased significantly on DST 200 mg/kg and 50 mg/kg. 8. In joints, levels of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, cyclo-oxygenase-2(COX-2), NOS-II were decreased on DST 200 mg/kg and DST 50 mg/kg. 9. In analysing of cytokine in CD3/CD28 activated spleen, IL-17 was decreased significantly, IL-4 was increased significantly $INF-{\gamma}$ was decreased on DST 200 mg/kg. 10. In analysing of cytokine in collagen activated spleen, IL-17 were decreased significantly, IL-4 was increased significantly. Conclusions : This results demonstrated that DST suppressed the inflammatory progression of collagen-induced arthritis(CIA) mice and supported further studies are required to survey continuously in looking for the effective substance and mechanism in the future.

References

  1. 한방재활의학과학회. 한방재활의학. 제2판. 서울:군자출판사. 2005:83-4, 96-9.
  2. Kasper. Harrison's 내과학. 서울:도서출판 MIP. 2006:179, 1777-85, 2148-57.
  3. 강호영, 김덕룡, 이만형, 권병석, 정헌택, 이원하, 김강주, 석경호, 백상기, 박주홍, 김영호, 조영준, 최태진. 면역학. 6판. 서울:월드사이언스. 2008:411, 414.
  4. Choy EH, Panayi GS. Cytokine pathway and joint inflammation in rheumatoid arthritis. N Engle Journl Med. 2001;344:907-16. https://doi.org/10.1056/NEJM200103223441207
  5. 대한정형외과학회. 정형외과학. 제6판. 서울:최신의학사. 2006:175-6, 226, 232-47, 253-8.
  6. 배상철. 국내 류마티스질환의 유병률 조사현황. 대한류마티스학회지. 2010;17(1):1-3.
  7. 보건복지부. 질병관리본부. 국민건강영양조사 제4기 1차년도(2007). 질병관리본부. 2008:76.
  8. 이학인, 양재하, 권순주. 류마토이드 관절염의 동서의학적 고찰. 경산대 제한동의학술원 논문집. 1999;4(1):199-209.
  9. 李挺. 編註醫學入門. 서울:大星文化社. 1989:369-71, 523.
  10. 王燾. 外臺秘要方. 서울:大星文化社. 1983:424.
  11. 巢元方. 諸病源候論. 人民衛生出版社. 1982:5-8.
  12. 권재식. 痺證. 서울:정담. 1993:207-8, 214-5, 219-22, 270.
  13. Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen. An experimantal model of arthritis. J. Exp Med. 1977;146(1):857-68. https://doi.org/10.1084/jem.146.3.857
  14. 박장우. DBA/1J 생쥐에서 蒼朮桃仁湯加味方이 콜라겐 유도 관절염 억제에 미치는 효과에 관한 연구. 대전대학교대학원. 2009.
  15. 김민기, 오민석. 加味大羌活湯이 collagen II로 유발된 관절염에 미치는 영향. 한방재활의학과학회지. 2009;19(2):89-102.
  16. 조중현, 권오곤, 우창훈, 안희덕. Collagen으로 유발된 마우스의 관절염에 대한 薏苡仁湯 추출물의 억제효과. 한방재활의학과학회지. 2010;20(1):37-60.
  17. 張仲景. 仲景全書, 傷寒論. 서울:대성문화사. 1993:179.
  18. 김동희, 김성훈, 김정범, 문준전, 맹웅재, 박종현, 신영일, 안규석, 엄현섭, 이선구, 지규용, 최달영. 傷寒論精解. 서울:한의문화사. 2003:668-9.
  19. 小林梧, 金久保好男. 약물의 혈액 점도에 미치는 영향(V)-當歸四逆加吳茱萸生薑湯에 의한 말초순환 개선효과-신약과 임상. 1982;31(1):123.
  20. 이정원. 當歸四逆加吳茱萸生薑湯이 백서의 갑상선기능저하증에 미치는 영향. 대전대학교대학원. 2001.
  21. 조윤철. 當歸四逆加吳茱萸生薑湯이 흰쥐의 adjuvant 유발관절염에 미치는 영향. 세명대학교대학원. 2004.
  22. 李敏燮, 金聖勳, 金仁洛. 當歸四逆加吳茱萸生薑湯을 中心으로 한 脫疽 臨床例에 對한 小考. 대전대학교한의학연구소 논문집. 1998;7(1):435-43.
  23. 노영범, 노의준. 도해유취방. 서울:복치의학회출판국. 2010:496.
  24. Bendele A, McComb J, Gould T. Animal model of arthritis. Relevance to Human Disease. Toxicologic pathology. 1999;27(1):134-42. https://doi.org/10.1177/019262339902700125
  25. Lacey D, Sampey A, Mitchell R, Bucala R, Santos L, Leech M. Control of fibroblast-like synoviocyte proliferation by macrophage migration inhibitory factor. Arthritis Rheum. 2003;48:103-9. https://doi.org/10.1002/art.10733
  26. 정태호, 김정철, 김문규. 최신면역학 강의. 대구:경북대학교출판부. 1996:2, 10, 25, 77, 193, 200, 211-2, 215, 232-5, 248, 357.
  27. 김세종. 면역학. 서울:고려의학. 1994:3, 8, 18, 25-6, 28, 31-2, 114, 134, 148-50, 157-8, 206.
  28. Miossec P. An update on the cytokine network in rheumatoid arthritis. Curr Opin Rheumatol. 2004;16:218-22. https://doi.org/10.1097/00002281-200405000-00009
  29. Danielle M. The effect of a T cell-specific NF-kB inhibitor on in vitro cytokine production and collagen-induced arthritis. The Journal of Immunology. 2000;165:1652-8. https://doi.org/10.4049/jimmunol.165.3.1652
  30. Sato K, Suematsu A, Okamoto K. Yamaguchi A, Morishita Y, Kadono Y. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destrction. J Exp Med. 2006;203:2673-82. https://doi.org/10.1084/jem.20061775
  31. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910-4. https://doi.org/10.1074/jbc.M207577200
  32. 이수곤, 이지수, 이찬희. 류마티스 관절염의 치료: 파라다임(paradigm)의 변화. 대한류마티스학회지. 1996;3(2):103-9.
  33. Boers M. Understanding the window of opportunity concept in early rheumatoid arthritis. Arthritis Rheum. 2003;48(7):1771-4. https://doi.org/10.1002/art.11156
  34. 최용훈, 윤일지. 류마토이드 관절염의 연구동향에 대한 小考-2004년 이후의 국내 학위논문 및 학회지 논문을 중심으로. 한방재활의학과학회지. 2009;19(2):125-56.
  35. 공상은, 오민석. 海桐皮復合方이 collagen II 유발 관절염에 미치는 실험적 연구. 한방재활의학과학회지. 2008;18(2):1-15.
  36. 제병선, 박장우, 윤일지, 오민석. 當歸川芎湯加味方이 관절염에 미치는 영향. 한방재활의학과학회지. 2006;16(1):109-26.
  37. 박은숙, 윤일지. 蒼朮桃仁湯加味方이 류마토이드 관절염에 미치는 실험적 연구. 한방재활의학과학회지. 2009;19(4):1-18.
  38. 박원. 류마티스 관절염 환자에서 MTX 부작용의 원인과 엽산대사. 대한내과학회지. 2004;67(2):109-12.
  39. 제이슨. 관절염치료법. 서울:집사재. 1997:23-6.
  40. 최도영, 이재동, 백용현, 이송실, 유명철, 한정수, 양형인, 박상도, 유미현, 박은경, 박동석. 류마티스 관절염에 대한 한약의 면역학적 연구동향. 대한침구학회지. 2004;21(4):177-96.
  41. 久保道德. 韓方醫藥學. 서울:東南出版社. 1984:89-93.
  42. 박경아, 이원택, 이종은, 박승화 공역. 조직학. 서울:고려의학. 1999:2-4.
  43. Gordon Starkebaum. Rheumatoid Arthritis. Science and Medicine. 1998;5(2):111-23.
  44. Franklin H. Epstein. Cytokine pathway and joint inflammation in RA. Eng. J Med. 2001;344(12):907.
  45. Jonathan K, Tal M, Ehud H, Iftach S, Ethan S, Michal S. Naturally occurring $CD4^{+}/CD25^{+}$ regulatory T cells suppress the ability to withstand injury to the central nervous system. The national academy of sciences. 2002;99(24):15620-5. https://doi.org/10.1073/pnas.232565399
  46. Charbonnier LM, van Duivenvoorde LM, Apparailly F, Cantos C, Han WG, Noel D, Dupenay C, Huizinga TW, Toes RE, Jorgensen C, Louis-Plence P. Immature dendritic cell suppress collagen-induced arthritis by in vivo expansion of CD49b+ regulatory T cell. J Immunol. 2006;177(6):3806-13. https://doi.org/10.4049/jimmunol.177.6.3806
  47. Gavin MA, Clarke SR, Negrou E, Gallegos A, Rudensky A. Homeostasis and anergy of $CD4^{+}/CD25^{+}$ suppressor T cells in vivo. Nat Immunol. 2002;3(1):33-41. https://doi.org/10.1038/ni743
  48. Ziegler SF. The activation antigen CD69. Stem Cells. 1994;12(5):456-65. https://doi.org/10.1002/stem.5530120502
  49. 박소영, 강대영. CD11c 항체가 Lipopolysaccharide에 의한 국소적 Shwartzman 반응의 유발에 미치는 영향. 충남의대잡지. 2000;27(2):169-82.
  50. Thirumalai Ramalingam. Kinetics of cellular responses to intraperironeal brugia pahangi infecrions in normal and immunodeficient mice. Infention And Immunity. 2003:4361-7.
  51. Mosby international Ltd. Cash couse. Immune blood and Lymphatic Systems. t서울:한우리. 2000:17-21.
  52. Kong YY. Activated T cells regulate bone loss and joint dectruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402:304-9. https://doi.org/10.1038/46303
  53. Mori L. Attenuation of collagen-induced arthritis in 55-kDa TNF receptor type 1(TNFR1)-IgG1-treated and TNFR1-deficient mice. J. Immunol. 1996;157:3178-82.
  54. Marc Feldmann. Role of cytokines in reumatoid arthritis. London. Annu. Rev. Immunol. 1996;14:398-9.
  55. Janeway CA, Travers P, Hunt S, Walport M. Immunobiology. The immune system in health and disease. Current Biology. 1997:Figs. 8.7, 8.14, 9-10.
  56. Okumoto H, Matsuda T, Turner M. The synovial expression and serum levels of IL-6, IL-11, leukemia inhibitory factor and oncostation in rheumatoid arthritis. Arthritis and rheumatism. 1997;40:1096-105. https://doi.org/10.1002/art.1780400614
  57. Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu. Rev. Med. 1994;45:491-503. https://doi.org/10.1146/annurev.med.45.1.491
  58. Moon TC, Murakami M, Ashraf MD, Kudo I, Chang HW. Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial lipopolysaccharide that acts in synergy with c-kit ligand and Fc epsilon receptor I crosslinking in cultured mast cells. Cell. Immunol. 1998;185:146-52. https://doi.org/10.1006/cimm.1998.1284
  59. Carla Biondi, Biondi C, Fiorini S, Pavan B, Ferretti ME. Interactions between the nitric oxide and prostaglandin E2 biosynthetic pathways in human amnion-like WISH cells. Journal of reproductive immunology. 2003;60(1):35-52. https://doi.org/10.1016/S0165-0378(03)00080-9
  60. Brahn E, Peacock DJ, Banquerigo ML, Liu DY. Effects of tumor necrosis factor alpha(TNF-{$\alpha}$) on collagen arthritis. Lymphokine Cyfukine Res. 1992;11:253.
  61. 이준희, 김근태, 류선, 김주인, 백승훈, 김성일. 류마토이드 관절염 동물 모델에서 활막의 RANKL/OPG mRNA 발현비율 및 IL-17의 효과. 대한류마토이드학회지. 2006;13(2):123-31.
  62. Abbas AK, Lichtman AH, Pober JS. Cellular and molecular immunology. 4th ed. Philadelpia:W.B Saunders. 2000:260-1.
  63. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implication for health and disease. Altern Med Rev. 2003;8(3):223-46.