The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
권호 표지

Effects of Jakyakkamchobuja-tang (芍藥甘草附子湯) on Papain-induced Osteoarthritis in Mice

Papain으로 유도된 골관절염 생쥐 모델에서 작약감초부자탕(芍藥甘草附子湯)의 항골관절염 효능에 관한 연구

  • Lee, Jung-Min (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dae-Jeon University) ;
  • Hong, Seo-Young (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dae-Jeon University) ;
  • Oh, Min-Seok (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Dae-Jeon University)
  • 이정민 (대전대학교 한의과대학 한방재활의학과교실) ;
  • 홍서영 (대전대학교 한의과대학 한방재활의학과교실) ;
  • 오민석 (대전대학교 한의과대학 한방재활의학과교실)
  • Received : 2012.10.15
  • Accepted : 2013.01.07
  • Published : 2013.03.31
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Abstract

Objectives: This study was intended to clarify how Jakyakkamchobuja-tang (hereinafter referred to JKBT) affects mice of C57BL/10 whose osteoarthritis was induced by papain. Methods: Osteoarthritis was induced in mice by injecting papain in the knee joint. Mice were divided into 4 groups (n=6). The normal group were not treated at all whereas the control group (OAC-control) were induced for osteoarthritis by papain and oral medicated with 200 ul of physiological saline per day. The positive comparison group (OAC-$Joins^{(R)}$) were injected with papain and after 7 days, 100 mg/kg of $Joins^{(R)}$ were medicated with 200 ul of physiological saline mixed. The experimental group (OAC-JKBT) were injected with papain and after 7 days were medicated with 400 mg/kg of JKBT mixed with 200 ul of physiological saline. OAC-$Joins^{(R)}$ and OAC-JKBT were oral medicated for each substance for a total of 4 weeks, once per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the function of liver and kidney, inflammation cytokine values within serum, degree of revelation for inflammation cytokine genes, immune cells within blood, metabolism of arachidonic acid and amount of cartilage were measured and histopathological variations for knee joint structures were observed. Results: Functions of liver and kidney were not affected. IL-$1{\beta}$ (interleukin-$1{\beta}$), MCP-1 (monocyte chemoattractant protein-1) and TNF-${\alpha}$ (tumor necrosis factor-${\alpha}$) were significantly reduced and IL-6 (interleukin-6) was also reduced but not significantly. After analyzing inflammation cytokine in joints with mRNA (messenger ribonucleic acid), revelation of IL-6, TNF-${\alpha}$, COX-2 (cyclooxygenase-2) and iNOS-II (inducible nitric oxide synthase-II) were all significantly reduced. Revelation of IL-$1{\beta}$ gene was also reduced but not significantly. Neutrophil for WBC (white blood cell) within serum was significantly reduced; monocyte was also reduced but not significantly. PGE2 (prostaglandin E2), TXB2 (thromboxane B2) were significantly reduced and LTB4 (leukotriene B4) was also reduced but not significantly. Destruction of cartilage on micro CT (computed tomography)-arthrography was reduced but had no significant differences. In terms of histopathology, infiltration of inflammation, proliferation of synovial membrane, subsidence of cartilage and bone due to penetration of excessive formation of synovial cell and destruction of cartilage were small (H&E (hematoxylin and eosin), safranine O staining). Conclusions: Based on these results, Jakyakkamchobuja-tang (JKBT) is believed to be useful for suppressing the progress of osteoarthritis and its treatments because of its anti-inflammatory effects and alleviation of pain with histopathological effective efficacy.

Keywords

References

  1. WHO. Chronic rheumatic conditions. 2011. Avai lable at: URL:http://www.who. int/chp/topics/rhe umatic/en/.
  2. 대한정형외과학회. 정형외과학. 제6판. 서울:최신의학사. 2006:253-261.
  3. 통계청. 국가통계포털. 주제별통계. 2011. Availa ble at: URL:http://kosis.kr/abroad /abroad_01Lis t.jsp.
  4. Kim HA. Clinical Investigation of Osteoarthritis. The Journal of the Korean Rheumatism Association. 2000;7(3):205-211.
  5. Kasper et al. 대한내과학회 해리슨내과학 편찬위원회편. Harrison's 내과학. 서울:도서출판 MIP. 2006:2083-2084, 2222-2227.
  6. 한방재활의학과학회. 한방재활의학. 제3판. 서울:군자출판사. 2011:84; 97.
  7. Lee GM, Kim DH, Kim HW, Cho NG, Choi YS, Kim HS, et al. The Clinical Study on the Effect of Acupotomy Osteoarthritis on Knee Using "Five-Finger Placed to Marking Position. The Journal of Korean Acupuncture & Moxibustion Society. 2008;25(4):197-202.
  8. Park IS, Jung CY, Jang MK, Kang MS, Lee SW, Kim EJ, et al. A Randomized Clinical Trial of Local Acupoints Compared with Distal Acupoints in Degenerative Osteoarthritis on Knee. The Journal of Korean Acupuncture & Moxibustion Society. 2008;25(2):227-242.
  9. Choi JH, Ko YJ, Lee SH, Kang SK, Lee YH. Case Report of Moxibustion Therapy for a Osteoarthritis Patient with Stroke. The Journal of Korean Spine & Joint Association. 2005;2(1): 27-23.
  10. Kim EJ, Lee SD, Jung CY, Yoon EH, Jang MG, Nam DW, et al. Review of Randomized Controlled Trials on Ideal Acupuncture Treatment for Degenerative Knee Osteoarthtritis. The Journal of Korean Acupuncture & Moxibustion Society. 2009; 26(2):125-145.
  11. Park EJ, Shin JC, Na GH, Lee DH, Han SG, Yoon YC, et al. Study on clinical effects Cervus elaphus Herbal-acupuncture on Osteoarthritis in Knee joint. The Journal of Korean Acupuncture & Moxibustion Society 2004;21(2): 275-286.
  12. Park KB, Song KH, Lee JS, Jo JH. Study on Clinical Effects of Homnis Placenta Herbal Acupuncture on Osteoarthritis of Knee Joint. The Journal of Korean Acupuncture & Moxibustion Society. 2006;23(4):163-173.
  13. Park HS, Son SH. Effects of Paeonia Radix Rubra aqua-acupucture on Adijuvant arthritis in rats. The Journal of Korean Acupuncture & Moxibustion Society. 2000; 17(1):153-168.
  14. Kim HB, Lee RM, Lee MH, Choi YS, Kim JG, Lee YH, et al. Comparative Study of Effects of 'Intramuscular Bee Venom Herbal Acupuncture' and 'Intracutaneous Bee Venom Herbal Acupuncture' in Knee Osteoarthritis Patients. The Journal of Korean Acupuncture & Moxibustion Society. 2008;25(2):151-164.
  15. Kim DH, Jeong SH, Seo IB, Kim SJ. Suppression effects of Sopunghwalhyeol-tang(Shufenghuoxie -tang) on the Monosodiun Iodoacetate-induced o steoarthritis in rats. Journal of Oriental Rehabilita tion Medicine. 2011;21(1):57-77.
  16. Kim JY, Kim SJ, Seo IB, Jeong SH. Effects if Buja-tang treatment on the early change of the Monosodiun iodoacetate-induced osteoarthritis in rats. Journal of Oriental Rehabilitation Medicine. 2011;21(2):87-100.
  17. Ahn HB, Kim SJ, Seo IB, Jeong SH. Effects if Imyo-san treatment on the early change of the Monosodiun iodoacetate-induced osteoarthritis in rats. Journal of Oriental Rehabilitation Medicine. 2010;20(3): 13-26.
  18. Pack DS, Jeong SH, Kim SJ, Seo IB. Effects if Gagamsosokmyeong-tang(Jiajianxiaoxuming-tan g) treatment on the early change of the Monosodiun iodoacetate-induced osteoarthritis in rats. Journal of Oriental Rehabilitation Medicine. 2011;21(4):49-65.
  19. Kim TE, Park JW, Park RJ, Sun JG. A study on the EGT(Extra Gigong Therapy) with Degrade Osteoarthritis. Journal of Medical Gi-Gong. 2006;9(1):217-237.
  20. Sung HJ, Kim EH, Hwang JW, Ryu CY. Clinical Study on Effect of Rainbow Power Therapy on Osteoarthritis in Knee Joint. The Korean Journal of Meridian & Acupoint. 2003;20(4):85-93.
  21. 박병희 역. 임상응용 상한론해설. 강원:의방출판사. 2004:220-222.
  22. Chang Y, Wei W, Zhang L, Xu HM. Effects and mechanisms of total glucosides of paeony on synoviocytes activities in rat collagen-induced arthritis. J Ethnopharmacol. 2009;121:43-48. https://doi.org/10.1016/j.jep.2008.09.028
  23. Tsai HY, Lin HY, Fong YC, Wu JB, Chen YF, Tsuzuki M, et al. Paeonol inhibits RANKL-induc ed osteoclastogenesis by inhibiting ERK, p38 and NF-kappaB pathway. Eur J Pharmacol. 2008;558:124-133.
  24. Amagaya S, Sugishita E, Ogihara Y, Ogawa S, Okada K, Aizawa T. Comparative studies of the steroisomers of glycyrrhetinic acid on antiinflammatory activities. J Pharmacobiodyn. 1984;7:923-928. https://doi.org/10.1248/bpb1978.7.923
  25. Koh DK, Yun JM, Lee TH. Effects of Aconiti Tuber on the Change of Interleukin-6 and TNF- $\alpha$Level induced by LPS I.C.V. Injection in Mice. Korean Journal of Oriental Medical Prescription. 2004;12(1):195-208.
  26. Kim YH, Yim YK, Lee H. The Effects of Herbal-acupuncture with Aconiti Iateralis Preparata Radix solutionon Collagen-induced arthritis. The Korean Journal of Meridian & Acupoint. 2006;23(2):137-154.
  27. Lee KO, Kuk YB, Yun YG. Effects of Jakyakgamchotang extract on the Analgesic effect in Mice. Korean Journal of Oriental Medical Prescription. 2003;11(1):161-170.
  28. Kim BW. Anti-inflammatory Effect of Jakyakgamcho-tang. Korean. J. Oriental. Int. Med. 2010;31(2):177-183.
  29. Xue L, Zhang HY, Qin L, Wang XC, Wang L. Effects of chuanwu and baishao used separately or in combination on adjuvant arthritis in rats. Zhongguo Zhong Yao Za Zhi. 2000;25(3):175-178.
  30. 대한병리학회. 병리학. 서울:고문사. 2003: 1167-1169.
  31. Murphy JM, Dixon K, Beck S, Fabian D, Feldman A, Barry F. Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Arthritis Rheum. 2002;46(3):704-713. https://doi.org/10.1002/art.10118
  32. Buckwalter JA, Mankin HJ. Articular cartilage: degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr Course Lect. 1998;47:487-504.
  33. Lee DY, Moon HS, Cho KH, Cheon JE. Effect of Glucosamine for knee osteoarthritis. Journal of Korean Knee Society. 2001;13(1):130-136.
  34. Yang CH. Gastrointestinal disorders associated with non-steroidal anti-inflammatory drugs (NSAIDs). Dongguk Journal of Medicine. 2003;10(2):190-199.
  35. Lee YJ. Medical treatment of osteoarthritis. The Korean Journal of Medicine. 2004;67(5):564-567.
  36. Huskisson EC, Berry H, Gishen P, Jubb RW, Whitehead J. Effects of antiinflammatory drugs on the progression of osteoarthritis of the knee. LINK Study Group. Longitudinal Investigation of Nonsteroidal Anti- inflammatory Drugs in Knee Osteoarthritis. J Rheumatol. 1995 Oct; 22(10):1941-1946.
  37. Bae DK, Chung KW, Kim JM, Kwon CH, Pack TK. Immunohistochemical Staining for Type Ⅱ Collagen in Regenerated Cartilage after Microfracture Surgery. Journal of Korean Orthopaedic Research Society. 2000;3(1):1-4.
  38. 양유걸. 황제내경소문해석. 서울:일중사. 1991:
  39. 김윤경. 가감과 창방의 현대적 의미. 한국한의학 연구원 연구보고서 전통적 임상기술의 보호 및 BD구축(I). 2003;12:127-137.
  40. SK 케미칼. 2011. Available at: URL:http://www. skchemicals.com/korean2/ product/life/pharm/M edicine01_04.asp.
  41. 이종인. 古方撰次. 부산:교정의서국. 2007:193-194.
  42. Hulejova H, Baresova V, Klezlb Z, Polanska M, Adama M, Senolta L. Increased level of cytokines and matrix metalloproteinases in osteoarthritic subchondral bone. Cytokine. 2007;38(3):151-156. https://doi.org/10.1016/j.cyto.2007.06.001
  43. Lopez-Armada MJ, Carames B, Martín MA, Cillero-Pastor B, Lires-Dean M, Fuentes- Boquete I, et al. Mitochondrial activity is modulated by TNFalpha and IL-1beta in normal human chondrocyte cells. Osteoarthritis Cartilage. 2006;14(10):1011-1022. https://doi.org/10.1016/j.joca.2006.03.008
  44. 황상익. 면역의 의미론. 서울:하늘과학문고. 1998:43; 45; 69; 92.
  45. Martel-Pelletier J, Pelletier JP, Fahmi H. Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum. 2003;33(3): 155-167. https://doi.org/10.1016/S0049-0172(03)00134-3
  46. Simi T. Inhibition of IL-6, IL-10 signaling and star activation by inflammatory and stress pathways. J Immunal. 2000;165:5227-5237.
  47. Katherine L, Manson Terry L, Moore James M. Cytokine level in synovial fluid and serum of patient with Juvennile rheumatoidal arthritis. J Rheumatol. 1994;21:2359-2363.
  48. Kim JK, Oh MS. Effects of Gwanjul8-bang in collagen induced arthritis in DBA/1J mice. Journal of Oriental Rehabilitation Medicine. 2010;20(2):17-34.
  49. Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment on rheumatoid arthritis. Lancet. 2007;370(9602): 1861-1874. https://doi.org/10.1016/S0140-6736(07)60784-3
  50. 임창경. Anti-rhenmatiod arthritis effects of I-Myo-San water ectract. The Korean Journal of Oriental Medical Prescription. 2009;17(1): 99-111.
  51. Harizi H, Corcuff JB, Gualde N. Arachidonicacid- derived eicosanoids: roles in biology and immunopathology. Trends in Molecular Medicine. 2008;14(10):461-469. https://doi.org/10.1016/j.molmed.2008.08.005
  52. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, patho-physiology, and pharmacolog y. Pharmacol Rev. 1991;43(2): 109-142.
  53. Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. J Biol Chem. 1994;269(19): 13725-13728.
  54. 김진호, 한태륜. 재활의학. 서울:군자출판사. 2006:501-524.
  55. 이귀녕, 권오헌. 임상병리파일 제3판. 서울:의학 문화사. 2003:95; 102; 334; 718-720; 754; 1075; 1080; 1173; 1192; 1198; 1227.
  56. Baek DH, Jahng J, Ha KY. Effect of Leukotriene B4 and B2 on Lumbar Nerve Roots in Rat. Journal of Korean Society of Spine Surgery. 2001;8(1):8-14. https://doi.org/10.4184/jkss.2001.8.1.8
  57. Horton JK, Williams AS, Smith-Phillips Z, Martin RC, O'Beirne G. Intracellular measurement of prostaglandin E2: effect of anti-inflammatory drugs on cyclooxygenase activity and prostanoid expression. Anal Biochem. 1999;271(1):18-28. https://doi.org/10.1006/abio.1999.4118
  58. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. Cyclooxygenase in biology and disease. FASEB J. 1998;12:1063-1073.
  59. Kontny E, Rudnicka W, Kowalczewski J, Marcinkiewicz J, Maslinski W. Selective inhibition of cyclooxygenase 2-generated prostaglandin E2 synthesis in rheumatoid arthritis synoviocytes by taurine chloramine. Arthritis and Rheumatism. 2003;48(6):1551-1555. https://doi.org/10.1002/art.10975
  60. Ales J, Alenka S, Barbara L, Janos B, Alenka NS. Serum thromboxane B2(TXB2) determination is influenced by sample incubation temperature in healthy beagle dogs. ACTA VET. BRNO. 2009;78:223-228. https://doi.org/10.2754/avb200978020223
  61. Yokomizo T, Izumi T, Shimizu T. Leukotriene B4: metabolism and signal transduction. Arch Biochem Biophys. 2001;385(2):231-241. https://doi.org/10.1006/abbi.2000.2168