DOI QR코드

DOI QR Code

Effects of Gyejigabuja-tang on MIA-induced Osteoarthritis in Rats

계지가부자탕(桂枝加附子湯)이 MIA로 유도된 골관절염 Rat 모델에 미치는 영향

  • Won, Je-Hoon (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Woo, Chang-Hoon (Department of Rehabilitation Medicine of Korean Medicine, College of Korean Medicine, Daegu Haany University)
  • 원제훈 (대구한의대학교 한의과대학 한방재활의학과교실) ;
  • 우창훈 (대구한의대학교 한의과대학 한방재활의학과교실)
  • Received : 2015.03.17
  • Accepted : 2015.03.28
  • Published : 2015.04.30

Abstract

Objectives This study was carried out to investigate the effects of Gyejigabuja-tang extracts on the Monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of MIA into knee joint cavity of rats. Rats are divided into 4 groups (normal, control, positive comparison group, GBT group, each n=5). Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and oral medicated with distilled water. Positive comparison group was injected with MIA and taken Joins tablet 25 mg/kg. GBT group was injected with MIA and taken Gyejigabuja-tang extracts 300 mg/kg. Positive comparison group and GBT group were oral medicated for each substance once a day for 4 weeks. ALT, AST and creatinine were evaluated for hepatotoxicity and nephrotoxicity. Hind paw weight bearing ability was examined and inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), $PGE_2$, $LTB_4$, osteocalcin and deoxypyridinoline (DPD) within serum were analysed. Knee joint structures were observed by Hematoxylin & Eosin (H&E), Safranin-O staining method. Results 1. Function of liver and kidney was not affected. 2. Hind paw weight bearing ability was significantly improved. 3. IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ in experimental group were significantly decreased compared with control group. 4. $PGE_2$, $LTB_4$, Osteocalcin and DPD in experimental group were decreased compared with control group. 5. In histopathologic observation, injury on synovial membrane and cartilage of experimental group was lesser than control group (H&E, Safranin-O staining). Conclusions Based on these results, it can be suggested that Gyejigabuja-tang has anti-inflammation effects on the MIA-induced osteoarthritis in rats.

Keywords

Gyejigabuja-tang;Osteoarthritis;Anti-inflammation effect;Monosodium iodoacetate (MIA)

References

  1. 한방재활의학과학회. 한방재활의학. 제3판. 서울:군자출판사. 2011:84-98.
  2. 대한정형외과학회. 정형외과학. 제6판. 서울:최신의학사. 2006:253-61.
  3. Bondeson J, Blom AB, Wainwright S, Hughes C, Bruce CB & van den Berg WB. The role of synovial macro phages and macrophage-produced mediatiors in driving inflammatory and destructive responses in osteoarthritis. Arithritis Rheum. 2010;62(3):647-57.
  4. Combe R, Bramwell S, Field MJ. The monosodium iodoacetate model of osteoarthritis. Neurosci Lett. 2004; 370(2-3):236-40. https://doi.org/10.1016/j.neulet.2004.08.023
  5. 이은정, 오민석. 健步丹이 MIA로 유도된 골관절염 Rat에 미치는 영향. 한방재활의학과학회지. 2014;24(2):51-64.
  6. 김대훈, 강성인, 송민영, 최진봉, 배길준, 한정석, 양미성, 신용진. 방기황기탕이 Monosodium Iodoacetate로 유발된 흰쥐의 골관절염에 미치는 영향. 한방재활의학과학회지. 2014;24(2):15-29.
  7. 안순선, 허동석. 桂枝人蔘湯이 MIA로 유도된 골관절염 유발 Rat에 미치는 영향. 대한한의학회지. 2013;34(3):69-85.
  8. 김대형, 정수현, 서일복, 김순중. 疎風活血湯이 Monosodium Iodoacetate로 유발한 흰쥐의 골관절염 억제에 미치는 영향. 한방재활의학과학회지. 2011;21(1):57-77.
  9. 이숭인. 新古方撰次. 서울:군자출판사. 2012:37.
  10. 김진우, 박강인, 박경선, 이진무. 양측난소절제술 후 발생한 汗出過多를 주소로 하는 갱년기증후군 환자에 대한 桂 枝加附子湯 치험 1례. 대한한방부인과학회지 2013;26(4): 213-22.
  11. 방정균. 桂技加附子湯證에 대한 考察. 대한한의학원전학회지. 2006;19(2):53-9.
  12. 안병룡. 桂枝加附子湯 전탕액이 실험동물의 진통, 진경 및 혈관에 미치는 영향. 원광대학교 석사학위논문. 1995.
  13. 식품의약품안전처. 생약(한약)제제의 효력시험 가이드라인- 골관절염. Available URL from: http://www.mfds.go.kr/index.do?mid=1161&searchkey=notice_number&searchword=B1-2009-3-017&x=0&y=0.
  14. 한태륜, 방문석 외 57인. 재활의학. 제3판. 서울:군자출판사. 2009:905-35.
  15. 국민건강영양조사. 2013 국민건강통계. Available from: http://knhanes.cdc.go.kr/knhanes/index.do.
  16. Abbas AK, Lichtman AH. 세포분자면역학. 서울:범문사. 2004:243-88.
  17. 전국한의과대학 본초학 공동교재편찬위원회. 본초학. 서울: 영림사. 2007:154-5, 171-2, 372-4, 583-6, 634-5.
  18. 김동훈, 송춘호. 桂枝藥鍼이 Type 1 Hypersensitivity에 미치는 영향. 대한경락경혈학회지. 2009;26(1):125-37.
  19. 박히준, 이지숙, 이재동, 김남재, 표지희, 강전모, 최일환, 김수영, 심범상, 이제현, 임사비나. 계지의 항염 효과에 관한 연구. 대한한의학회지. 2005;26(2):140-51.
  20. 문진영. 작약 약침액이 tert-butyl hydroperoxide로 유도된 흰쥐 배양 간세포의 지질과산화반응 및 항산화효소 활성에 미치는 영향. 대한침구학회지. 2000;17(3):176-87.
  21. 임창수, 김갑성. 芍藥 藥鍼의 抗酸化 效能에 미치는 影響. 대한침구학회지. 1999;16(3):269-86.
  22. 고동균, 윤정문, 이태희. 附子가 Lipopolysaccharide의 뇌실 주입으로 유발된 생쥐의 혈중 IL-6와 TNF-$\alpha$ 변화에 미치는 영향. 대한한의학방제학회지. 2004;12(1):195-208.
  23. 김윤희, 임윤경, 이현. 附子藥鍼이 흰쥐의 Collagen 유발 관절염에 미치는 영향. 대한경락경혈학회지. 2006;23(2): 137-54.
  24. 류혜숙, 김진, 박상철, 김현숙. 생강추출물투여에 의한 마우스 비장세포 및 대식세포 활성효과. 한국영양학회지. 2004;37(9):780-5.
  25. 서운교, 정효원, 박용기. 생강 클로로포름 분획의 활성화된 腦神經膠細胞에서 염증반응 억제효과. 대한본초학회지. 2008;23(3):73-83.
  26. Al-Reza SM, Yoon JI, Kim HJ, Kim JS, Kang SC. Anti-inflammatory activity of seed essential oil from Zizyphus jujuba. Food and Chemical Toxicology. 2010;48:639-43. https://doi.org/10.1016/j.fct.2009.11.045
  27. 김예진. 추출용매에 따른 건대추 과육, 씨, 잎 추출물의 항산화 및 항암효과. 대구한의대학교 석사학위논문. 2010.
  28. 송상진, 배한호, 박양춘. 감초가 천식모델 생쥐의 plasma내 histamine과 폐조직내 cytokine 생성에 미치는 효과. 동의생리병리학회지. 2004;18(3):841-5.
  29. 김수정, 권대혁, 이종화. 감초의 에탄올 추출물의 항산화 활성 및 안정성 조사. 한국식품과학회지. 2006;38(4):584-8.
  30. Kalben DA, Blum U. Theoretisches Koncept and experimentelle bestatigung fur ein neues arthos modell amversuchstier. Arzneimittelforshung Drug Res. 1977;27:527-31.
  31. Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K. Mono-iodoacetate-induced histologic change of rat femorotibial joints : an animal model of osteoarthritis. Toxicol Pathol. 2003;31(6):619-24. https://doi.org/10.1080/01926230390241800
  32. 권영일 외 공저. 실험. 동물 임상병리학. 서울:아카데미아. 2009:42, 185.
  33. Bove SE, Calcaterra SL, Brooker RM, Huber CM, Guzman RE, Juneau PL, Schrier DJ, Kilgore KS. Weight bearing as a measurement of disease progression and efficacy of anti-inflammatory compounds in a monosodium iodoacetate- induced osteoarthritis. Osteoarthritis and cartilage. 2003;11:821-30. https://doi.org/10.1016/S1063-4584(03)00163-8
  34. Meydani SN. Dietary modulation of cytokine proproduction and biologic functions. Nutr Rev. 1990;48:361-9.
  35. Arend WP, Dayer JM. Inhibition of the production and effects of interleukin-1 and tumor necrosis factor $\alpha$ in rheumatoid arthritis. Arthritis Rheum. 1995;38:151-60. https://doi.org/10.1002/art.1780380202
  36. Liu M, Li J, Kong F, Lin J, Gao Y. Induction of immunomodulating cytokines by a new polysaccharidepeptide complex from culture mycelia of Lentinus edodes. Immunopharmacology. 1998;40:187-98. https://doi.org/10.1016/S0162-3109(98)00043-5
  37. Dinarello CA, Endres S, Meydani SN, Meydani M, Hellerstein MK. Interleukin-1, anorexia, and dietary fatty acids. Ann N Y. Acad Sci. 1990;587:332-8. https://doi.org/10.1111/j.1749-6632.1990.tb00174.x
  38. Nedwin GE, Svedersky LP, Bringman TS, Palladino MA Jr, Goeddel DV. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1987;135:2492-7.
  39. 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):1551-5. https://doi.org/10.1002/art.10975
  40. Harizi H, Corcuff JB, Gualde N. Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Trends in Molecular Medicine. 2008;14(10):461-9. https://doi.org/10.1016/j.molmed.2008.08.005
  41. Yokomizo T, Izumi T, Shimizu T. Leukotriene B4: metabolism and signal transduction. Arch Biochem Biophys. 2001;385(2):231-41. https://doi.org/10.1006/abbi.2000.2168
  42. 이용환, 박원, 김성수, 박보형, 송정수. 류마티스 관절염 환자에서 저용량 스테로이드 용법이 골대사에 미치는 영향. 대한류마티스학회지. 2003;10(3):293-9.
  43. 박준섭, 주영실, 최윤선, 정명아, 하형근, 정인수, 김시민, 김병준, 안규정, 최영길. 척추 골관절염 환자에서의 골밀도와 골다공증성 척추골절의 빈도와의 관계. 대한류마티스학회지. 2003;10(1):45-52.
  44. Rubinacci A1, Melzi R, Zampino M, Soldarini A, Villa I. Total and free deoxypyridinoline after acute osteoclast activity inhibition. Clin Chem. 1999;45(9):1510-6.
  45. 약품 검색 인터넷 서비스. 드러그인포. Available URL from: http://www.druginfo.co.kr/search2/search.aspx?q=joins.
  46. 송은규, 윤택림, 김재휴, 이삼규. 슬관절 골관절염 환자에서 조인스정의 유효성 및 안정성. 최신의학. 2002;45(9-10);121-7.