Suppress Effects of Euiiin-tang(yìyĭrén-tāng) Aqueous Extracts on Collagen Induced Arthritic(CIA) DBA/1 Mice

Collagen으로 유발된 마우스의 관절염에 대한 의이인탕(薏苡仁湯) 추출물의 억제 효과

  • Cho, Jung-Hyun (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • Kwon, O-Gon (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • Woo, Chang-Hoon (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • An, Hee-Duk (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Daegu Haany University)
  • 조중현 (대구한의대학교 한의과대학 한방재활의학과교실) ;
  • 권오곤 (대구한의대학교 한의과대학 한방재활의학과교실) ;
  • 우창훈 (대구한의대학교 한의과대학 한방재활의학과교실) ;
  • 안희덕 (대구한의대학교 한의과대학 한방재활의학과교실)
  • Received : 2009.12.18
  • Accepted : 2010.01.12
  • Published : 2010.01.31

Abstract

Objectives : The object of this study was to observe the favorable anti arthritic effects of Euiiin-tang($y{\grave{i}}y{\breve{i}}r{\acute{e}}n-t{\bar{a}}ng$) aqueous extract(EIITe), has been traditionally used in Korean medicine for treating rheumatoid arthritis on collagen induced arthritic(CIA) DBA/1 mice. Methods : In the present study, effects of EIITe on the releases of human tumor necrosis factor(TNF)-${\alpha}$, interleukin(IL)-$1{\beta}$, matrix metalloproteinase(MMP)-13 and production of Nitric oxide(NO) were observed by in vitro. In addition, to observe the effects on the CIA mice, three different dosages of EIITe, 300, 150 and 150 mg/kg were orally administered once a day for 18 days from 24hrs after antigen challenges(type II collagen) on 21 days after immunization using Type II collagen Freund's complete adjuvant. Six groups, each of 8 DBA/1 mice per group were used in the present study as follows. Changes on the body weights, macroscopic arthritis scores, splenic weights, splenic TNF-${\alpha}$ and IL-6 contents, articular cartilage(femur and tibia) collagen and glycosaminoglycans-chondroitin sulphate, sulphate and hyaluronic acid contents, histopathological observations(microscopic arthritis scores, thicknesses of femur and tibia cartilage thicknesses were monitored, compared to that of dexamethasone, a potent anti inflammatory agents, 1 mg/kg treated mice. Results : As results of collagen challenges, marked decreases of body weights and gains, articular cartilage collagen and glycosaminoglycan - chondroitin sulphate, sulphate and hyaluronic acid contents were observed with increases of macroscopic arthritis scores, splenic weights, splenic TNF-${\alpha}$ and IL-6 contents, articular cartilage(in the both femur and tibia) loss and damages. However, these CIA signs were significantly and dosages dependently inhibited by treatment of EIITe 300 and 150 mg/kg as compared with CIA control, respectively. In addition, the releases of TNF-${\alpha}$, IL-$1{\beta}$, NO and MMP-13 were markedly and dose dependently inhibited by treatment of EIITe, invitro. Although CIA were more favorably inhibited by treatment of dexamethasone 1 mg/kg as compared with EIITe 300 mg/kg, marked decreases of body weights were detected in dexamethasone 1 mg/kg treated mice. Conclusions : The results obtained in this study suggest that over 150 mg/kg of EIITe showed favorable anti arthritic effects on the CIA mediated by immunomodulatory and/or anti oxidative effects. However, detail mechanism studies should be conduced in future with the screening of the biological active compounds in this herb. lthough CIA were more favorably inhibited by treatment of dexamethasone 1 mg/kg as compared with EIITe 300 mg/kg, marked decreases of body weights were detected in dexamethasone 1 mg/kg treated mice, in the present study.

References

  1. Habashy RR, Abdel-Naim AB, Khalifa AE, Al-Azizi MM. Anti-inflammatory effects of jojoba liquid wax in experimental models. Pharmacol Res. 2005;51:95-105. https://doi.org/10.1016/j.phrs.2004.04.011
  2. 곽중문, 오민석, 박종오, 김동희. 류풍활혈탕가미방이 collagen으로 유발된 생쥐의 관절염 억제에 관한 연구. 동의생리병리학회지. 2002;16:810-7.
  3. Poole AR, Witter J, Roberts N, Piccolo F, Brandt R, Paquin J et al. Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate. Arthritis Rheum. 1990;33:790-9. https://doi.org/10.1002/art.1780330605
  4. Reddy GK, Dhar SC. Metabolism of glycosaminoglycans in tissues of adjuvant arthritic rat. Mol Cell Biochem. 1991;106:117-24.
  5. Hibbs JB, Taintor RR, Vavrin Z, Rachlin EM. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988;157:87-94. https://doi.org/10.1016/S0006-291X(88)80015-9
  6. Blanco FJ, Ochs RL, Schwarz H, Lotz M. Chondrocyte apoptosis induced by nitric oxide. Am J Pathol. 1995;146:75-85.
  7. Van Lent PL, Holthuysen AE, Van Rooijen N, Van De Putte LB, Van Den Berg WB. Local removal of phagocytic synovial lining cells by clodronate-liposomes decreases cartilage destruction during collagen type II arthritis. Ann Rheum Dis. 1998;57:408-13. https://doi.org/10.1136/ard.57.7.408
  8. Mimura T, Itoh M, Gohgi H, Suzuki N, Takeuchi K, Tsujikawa K, et al. Studies on pharmacological activation of human immunoglobulin G by chemical modification and active subfragments. XIII. Effect of carboxamidemethylated Fc fragment(CM-Fc) on type II collagen-induced arthritis in DBA/1J mice. Biol Pharm Bull. 1994;17:623-6. https://doi.org/10.1248/bpb.17.623
  9. Kang I, Lee WW, Lee Y. Modulation of collagen-induced arthritis by IL-4 and dexamethasone: the synergistic effect of IL-4 and dexamethasone on the resolution of CIA. Immunopharmacology. 2000;49:317-24. https://doi.org/10.1016/S0162-3109(00)00248-4
  10. Chang SH, Sung HC, Choi Y, Ko SY, Lee BE, Baek DH et al. Suppressive effect of AIF, a water extract from three herbs, on collagen-induced arthritis in mice. Int Immunopharmacol. 2005;5:1365-72. https://doi.org/10.1016/j.intimp.2005.02.019
  11. Department of Health, Education, and Welfare Publication(National Institute of Health). Guide for the care and use of laboratory animals. Washington, D.C.:National Academy Press. 1985:85-123.
  12. Trentham DE, Townes AS, Kang AH. Autoimmunity to type II collagen an experi-mental model of arthritis. J Exp Med. 1997;146:857-68.
  13. Brahn E, Banquerigo ML, Firestein G, Boyle DL, Salzman AL, Szabo C. Collagen induced arthritis:reversal by mercaptoethylguanidine, a novel anti-inflammatory agent with a combined mechanism of action. J Rheumatol. 1998;25:1785-93.
  14. Clark JC, Dass CR, Choong PF. Development of chondrosarcoma animal models for assessment of adjuvant therapy. ANZ J Surg. 2009;79:327-36. https://doi.org/10.1111/j.1445-2197.2009.04884.x
  15. Hotchkiss RS, Osborne DF, Lappas GD, Karl IE. Calcium antagonists decrease plasma and tissue concentrations of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-1 alpha in a mouse model of endotoxin. Shock. 1995;3:337-42.
  16. Leach AA. Notes on a modification of the Neuman and Logan method for the determination of the hydroxyproline. Biochem J. 1960;74:70-1. https://doi.org/10.1042/bj0740070
  17. Neuman RE, Logan MA. The determination of collagen and elastin in tissues. J Biol Chem. 1950;186:549-56.
  18. Neuman RE, Logan MA. The determination of hydroxyproline. J Biol Chem. 1950;184:299-306.
  19. Homer KA, Denbow L, Beighton D. Spectrophotometric method for the assay of glycosaminoglycans and glycosaminoglycan-depolymerizing enzymes. Anal Biochem. 1993;214:435-41. https://doi.org/10.1006/abio.1993.1520
  20. Ono Y, Inoue M, Mizukami H, Ogihara Y. Suppressive effect of Kanzo-bushi-to, a Kampo medicine, on collagen-induced arthritis. Biol Pharm Bull. 2004;27:1406-13. https://doi.org/10.1248/bpb.27.1406
  21. 김호연. 류머티스 관절염의 병인. 대한의학협회지. 1992;35:1198.
  22. James B, Wyngaarden C. Textbook of Medicine. Philadelphia:WASaunders. 1992:1508-15.
  23. 楊維傑 編著. 黃帝內經素問譯解. 台北市:台聯國風出版社.1984:95-6, 328-36.
  24. 張仲景. 金匱要略方論. 湖北:東方書店. 1950:30-9.
  25. 巢元方. 諸病源候論. 北京:人民衛生出版社. 1982:5-8.
  26. 王燾. 外臺秘要方. 서울:大星文化社. 1983:424.
  27. 陳無擇. 三因方. 大連:國風出版社. 1977:2-3.
  28. 김동현, 김형민, 류종훈, 엄재영, 김상찬, 양재하 외 3명. 한방약리학. 서울:신일상사. 2006:110-11,115-21,124-9,268-74,337-43,493-6,617-9,670-5.
  29. 白洪龍. 常見病症辨證診治槪要. 雲南省:雲南人民衛生出版社.1984:382-5.
  30. 朴病昆. 增補韓方臨床40年. 서울:大光文化社. 1989:343.
  31. 金定濟. 診療要覽. 서울:東洋醫學硏究所.1974:459-60.
  32. 皇甫中. 明醫指掌. 상해:人民衛生出版社. 1985:195.
  33. 李載熙. 圖說 韓方診療要方. 서울:癸丑文化社. 1977:570.
  34. 朴盛洙, 廉泰煥. 現代韓方講座. 서울:행림서원. 1996:276.
  35. 하현석. 한방처방의 구성과 해설. 서울:약업신문사. 1996:313.
  36. 김인락, 김호철, 국윤범, 박성주, 박용기, 박지하 외 12인. 本草學. 서울:圖書出版 永林社. 2007:152-5, 331-3, 349-51, 583-5, 629-31, 634-5.
  37. 尹泰汝. 加味薏苡仁湯의 投炎症作用에 對한 實驗的 硏究. 大韓韓方內科學會誌. 1976;1:64-9
  38. 申鉉大, 金性洙. 加味薏苡仁湯의 消炎效果 및 成分에 關한 硏究. 慶熙大學校 論文集. 1985;14:243-59.
  39. Samira S, Ferrand C, Peled A, Nagler A, Tovbin Y, Ben-Hur H et al. Tumor necrosis factor promotes human T-cell development in nonobese diabetic/severe combined immunodeficient mice. Stem Cells. 2004;22:1085-100. https://doi.org/10.1634/stemcells.22-6-1085
  40. Isaacs A. Lymphokines and Cytokines. In: Immunology an introduction(Tizard IR editor). 4th edition. Philadelphia:Saunders. 1995:155-69.
  41. Unanue ER. The Mononuclear-Phagocytic Sytem. In: Immunology an introduction (Tizard IR editor). 4th edition. Philadelphia:Saunders. 1995:61-74.
  42. Wolfe F, Hawley DJ. The longterm outcomes of rheumatoid arthritis: work disability: a prospective 18 year study of 823 patients. J Rheumatol. 1998;25:2108-17.
  43. Feldmann M, Brennan FM, Naini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol. 1996;14:397-440. https://doi.org/10.1146/annurev.immunol.14.1.397
  44. Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatol(Oxf). 2003;42(2):11-6.
  45. Coelho MG, Sabino KC, Dalmau SR. Immunomodulatory effects of sucupira(Pterodon pubescens) seed infusion on collagen-induced arthritis. Clin Exp Rheumatol. 2004;22:213-8.
  46. Inoue M, Ono Y, Mizukami H. Suppressive effect of Dai-bofu-to on collagen-induced arthritis. Biol Pharm Bull. 2004;27:857-62. https://doi.org/10.1248/bpb.27.857
  47. Gonzalez-Rey E, Chorny A, Varela N, O'Valle F, Delgado M. Therapeutic effect of urocortin on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of regulatory T cells. Arthritis Rheum. 2007;56:531-43. https://doi.org/10.1002/art.22394
  48. Lamb TJ, Voisine C, Koernig S, Egan CA, Harnett W, Langhorne J. The pathology of Plasmodium chabaudi infection is not ameliorated by the secreted filarial nematode immunomodulatory molecule, ES-62. Parasite Immunol. 2007;29:271-6. https://doi.org/10.1111/j.1365-3024.2007.00941.x
  49. Dai Q, Fang J, Zhang FS. Dual role of shikonin in early and late stages of collagen type II arthritis. Mol Biol Rep. 2009;36:1597-604. https://doi.org/10.1007/s11033-008-9356-7
  50. Haraoui B, Thonar EJ, Martel-Pelletier J, Goulet JR, Raynauld JP, Ouellet M et al. Serum keratan sulfate levels in rheumatoid arthritis: inverse correlation with radiographic staging. J Rheumatol. 1994;21:813-7.
  51. Thonar EJ, Lenz ME, Klintworth GK, Caterson B, Pachman LM, Glickman P et al. Quantification of keratan sulfate in blood as a marker of cartilage catabolism. Arthritis Rheum. 1985;28:1367-76. https://doi.org/10.1002/art.1780281209
  52. Emlen W, Niebur J, Flanders G, Rutledge J. Measurement o fserum hyaluronic acid in patients with rheumatoid arthritis: correlation with disease activity. J Rheumatol. 1996;23:974-8.
  53. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992;6:3051-64.
  54. Dinerman JL, Lowenstein CJ, Snyder SH. Molecular mechanisms of nitric oxide regulation. Potential relevance to cardiovascular disease. Circ Res. 1993;73:217-22. https://doi.org/10.1161/01.RES.73.2.217
  55. Szabo C. Alterations in nitric oxide production in various forms of circulatory shock. New Horiz. 1995;3:2-32.
  56. Southan GJ, Szabo C. Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem Pharmacol. 1996;51:383-94. https://doi.org/10.1016/0006-2952(95)02099-3
  57. Wright CD, Mulsch A, Busse R, Oswald H. Generation of nitric oxide by human neutrophils. Biochem Biophys Res Commun. 1989;160:813-9. https://doi.org/10.1016/0006-291X(89)92506-0
  58. Hartog A, Hulsman J, Garssen J. Locomotion and muscle mass measures in a murine model of collagen-induced arthritis. BMC Musculoskelet Disord. 2009;10:59. https://doi.org/10.1186/1471-2474-10-59
  59. Saadat F, Cuzzocrea S, Di Paola R, Pezeshki M, Khorramizadeh MR, Sedaghat M et al. Effect of pyrimethamine in experimental rheumatoid arthritis. Med Sci Monit. 2005;11(8):293-9.
  60. Liu M, Dai Y, Yao X, Li Y, Luo Y, Xia Y et al. Anti-rheumatoid arthritic effect of madecassoside on type II collagen-induced arthritis in mice. Int Immunopharmacol. 2008;8:1561-6. https://doi.org/10.1016/j.intimp.2008.06.011
  61. Yu DH, Kim MO, Kim SH, Shin MJ, Kim BS, Kim HJ et al. The therapeutic effect of extracellular superoxide dismutase(EC-SOD) mouse embryonic fibroblast(MEF) on collagen-induced arthritis(CIA) mice. Cell Transplant. 2008;17:1371-80. https://doi.org/10.3727/096368908787648029
  62. Van den Berg WB, Joosten LA, Helsen M, van de Loo FA. Amelioration of established murine collagen-induced arthritis with anti-IL-1 treatment. Clin Exp Immunol. 1994;95:237-43.
  63. Cho YG, Cho ML, Min SY, Kim HY. Type II collagen autoimmunity in a mouse model of human rheumatoid arthritis. Autoimmun Rev. 2007;7:65-70. https://doi.org/10.1016/j.autrev.2007.08.001
  64. Hegen M, Keith JC Jr, Collins M, Nickerson-Nutter CL. Utility of animal models for identification of potentia ltherapeutics for rheumatoid arthritis. Ann Rheum Dis. 2008;67:1505-15. https://doi.org/10.1136/ard.2007.076430
  65. Joosten LA, Helsen MM, Loo FA van de, Berg WB van den. Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice. A comparative study using anti-TNF alpha, anti-IL-1 alpha/beta, and IL-1Ra. Arthritis Rheum. 1996;39:797-809. https://doi.org/10.1002/art.1780390513
  66. Coelho MG, Reis PA, Gava VB, Marques PR, Gayer CR, Laranja GA et al. Anti-arthritic effect and subacute toxicological evaluation of Baccharis genistelloides aqueous extract. Toxicol Lett. 2004;154:69-80. https://doi.org/10.1016/j.toxlet.2004.07.004
  67. Ohori M, Takeuchi M, Maruki R, Nakajima H, Miyake H. FR180204, a novel and selective inhibitor of extracellular signal-regulated kinase, ameliorates collagen-induced arthritis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2007;374:311-6. https://doi.org/10.1007/s00210-006-0117-7
  68. Abdel-Salam OM, Baiuomy AR, El-batran S, Arbid MS. Evaluation of the anti-inflammti-in, anti-nociceptive and gastric effectn of Ginkgo biloba in the rat. Pharmacol Res. 2004;49:133-42. https://doi.org/10.1016/j.phrs.2003.08.004
  69. Alarcon GS. Epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am. 2001;27:269-82. https://doi.org/10.1016/S0889-857X(05)70201-5