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The Protective Effects of Mahaengeuigam-Tang against Monosodium Iodoacetate induced Osteoarthritis in Rats

마행의감탕(麻杏薏甘湯)이 골관절염 유발 흰쥐의 apoptosis 기전에 미치는 영향

  • Kim, Bum Hoi (Department of Anatomy, College of Korean Medicine and Research Institute of Korean Medicine, Dong-eui University)
  • 김범회 (동의대학교 한의과대학 한의학과, 동의대학교 한의학연구소)
  • Received : 2018.10.24
  • Accepted : 2018.11.20
  • Published : 2018.11.30

Abstract

Objectives : Mahaengeuigam-Tang (MHEGT) has been used as a traditional medicine for the treatment of rheumatic aerthritis, rheumatisim, eczema and asthma. The aim of this study was to investigate the molecular mechanisms of MHEGT for cartilage protection in monosodium iodoacetate(MIA)-induced osteoarthritis, particularly focusing on apoptosis. Method : Thirty young male Sprague-Dawley rats were used for the study. Rats were intra-articularly injected with 2 mg MIA in a total volume of 50 ㎕ saline. In MHEGT group, MHEGT extract was orally administered once daily to MIA-induced osteoarthritis rats, and rats of control group were given with saline only. At 4 weeks after MIA injection, all animals were sacrificed, and the histological changes and articular thickness were assessed by hematoxylin and eosin staining. Moreover, the immunohistochemical analyses of BAX and Bcl-2 were carried out. Results : The histomorphological examinations revealed that MHEGT reduced MIA-induced cartilage damage. And, MHEGT ameliorated the severity of cartilage surface damages after MIA injection. Furthermore, MHEGT suppressed the MIA-induced increases of pro-apoptotic BAX protein and increased the protein expression of anti-apoptotic Bcl-2 protein. Conclusion : These findings indicate that MHEGT protects against MIA-induced cartilage damage by inhibition of the apoptotic pathway, demonstrating significant protection of cartilage against osteoarthritis. These results suggest that MHEGT may potentially have clinical applications in the treatment of osteoarthritis.

Keywords

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Fig. 1. Body weight changes of rats in normal, control, and MHEGT groups

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Fig. 2. Comparisons of gross appearance of right tibial plateau in rat of normal, control, and MHEGT groups.

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Fig. 3. The histological analyses of right articular cartilage and bone changes in the rat of normal, control, and MHEGT groups.

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Fig. 4. Quantitative assessment of right articular cartilage thickness in the rat of normal, control, and MHEGT groups.

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Fig. 5. Representative photographs of BAX immunoactivities of right articular cartilage in Rats of normal, control, and MHEGT groups.

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Fig. 6. Representative photographs of Bcl-2 immunoactivities of articular cartilage in Rats of normal, control, and MHEGT groups.

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Fig. 6. Quantitative assessment of BAX and Bcl-2 immunohistochemistry in the rat of normal, control, and MHEGT groups.

Table 1. Herbal Composition of Mahaengeuigam-Tang(MHEGT)

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Table 2. BAX and Bcl-2 Immunohistochemistry of Normal, Control, and MHEGT groups.

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References

  1. Aigner T, Kurz B, Fukui N, Sandell L. Roles of chondrocytes in the pathogenesis of osteoarthritis. Curr Opin Rheumatol. 2002;14(5):578-84. https://doi.org/10.1097/00002281-200209000-00018
  2. Tsujii A, Nakamura N, Horibe S. Age-related changes in the knee meniscus. Knee. 2017;24(6):1262-70. https://doi.org/10.1016/j.knee.2017.08.001
  3. Rodriguez-Merchan EC. Topical therapies for knee osteoarthritis. Postgrad Med. 2018;130(7):607-12. https://doi.org/10.1080/00325481.2018.1505182
  4. Blanco FJ, Guitian R, Vazquez-Martul E, de Toro FJ, Galdo F. Osteoarthritis chondrocytes die by apoptosis. A possible pathway for osteoarthritis pathology. Arthritis Rheum. 1998;41(2):284-9. https://doi.org/10.1002/1529-0131(199802)41:2<284::AID-ART12>3.0.CO;2-T
  5. Kim DY, Taylor HW, Moore RM, Paulsen DB, Cho DY. Articular chondrocyte apoptosis in equine osteoarthritis. Vet J. 2003;166(1):52-7. https://doi.org/10.1016/S1090-0233(02)00305-2
  6. Thomas CM, Fuller CJ, Whittles CE, Sharif M. Chondrocyte death by apoptosis is associated with cartilage matrix degradation. Osteoarthritis Cartilage. 2007;15(1):27-34. https://doi.org/10.1016/j.joca.2006.06.012
  7. Lee SI, Kim DG, Kim YP, Roh SH, Park YJ, Joo YS. Herbal Formula Science. 2nd ed. Seoul:Young Lim Sa. 1994:47.
  8. Moon YH, Roh EM. Anti-Inflammatory, Analgesic and Antipyretic Actions of Mahaengeuigam-Tang. Korean Journal of Pharmacognosy. 2001;32(3): 242-7.
  9. Lee SG, Lee EJ, Park WD, KIm JB, Choi SW. Antioxidant and Anti-inflammatory Activities of Extracts from Korean Traditional Medicinal Prescriptions. Korean Journal of Food Science and Technology. 2011;43(5):624-32. https://doi.org/10.9721/KJFST.2011.43.5.624
  10. Kim TH, Lee CH. Effects of Mahangeuigam-Tang on Obesity-related Factors in Brain and Gastrointestinal Tract of Mice. Journal of physiology & pathology in Korean Medicine. 2012;26(2):166-74.
  11. Hong JM, Shin JK, Kim JY, Jang MJ, Park SK, Lee JH, Choi JH, Lee SM. BST106 Protects against Cartilage Damage by Inhibition of Apoptosis and Enhancement of Autophagy in Osteoarthritic Rats. Biol Pharm Bull. 2018; 41(8):1257-68. https://doi.org/10.1248/bpb.b18-00207
  12. Oh IS, Kim MK, Lee SH, Park SW, Kwon DG. The Change of Articular Cartilage Thickness of the Knee Joint Related to Age in Korean. Knee surgery & related research. 2005;17(1):1-7.
  13. Mora JC, Przkora R, Cruz-Almeida Y. Knee osteoarthritis:pathophysiology and current treatment modalities. J Pain Res. 2018;11: 2189-96. https://doi.org/10.2147/JPR.S154002
  14. Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J, Jordan KP. Current evidence on risk factors for knee osteoarthritis in older adults:a systematic review and meta-analysis. Osteoarthritis Cartilage. 2015; 23(4):507-15. https://doi.org/10.1016/j.joca.2014.11.019
  15. Pereira D, Ramos E, Branco J. Osteoarthritis. Acta Med Port. 2015;28(1):99-106.
  16. Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol. 2012; 8(11):665-73. https://doi.org/10.1038/nrrheum.2012.130
  17. Burr DB. The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998;10(3):256-62. https://doi.org/10.1097/00002281-199805000-00017
  18. Morais SV, Czeczko NG, Malafaia O, Ribas JM Filho, Garcia JB, Miguel MT, Zini C, Massignan AG. Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee. Acta Cir Bras. 2016;31(11):765-73. https://doi.org/10.1590/s0102-865020160110000010
  19. Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K. Monoiodoacetate induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints:an animal model of osteoarthritis. Toxicol Pathol. 2003;31(6):619-24. https://doi.org/10.1080/714044694
  20. Marker CL, Pomonis JD. The monosodium iodoacetate model of osteoarthritis pain in the rat. Methods Mol Biol. 2012;851:239-48.
  21. Wang ZM, Chen YC, Wang DP. Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced osteoarthritic pain in rats.Biomed Pharmacother. 2016;83:763-70. https://doi.org/10.1016/j.biopha.2016.06.050
  22. Junker S, Krumbholz G, Frommer KW, Rehart S, Steinmeyer J, Rickert M, Schett G, Muller-Ladner U, Neumann E. Differentiation of osteophyte types in osteoarthritis - proposal of a histological classification. Joint Bone Spine. 2016;83(1):63-7. https://doi.org/10.1016/j.jbspin.2015.04.008
  23. Takahashi I, Matsuzaki T, Hoso M. Long-term histopathological developments in knee-joint components in a rat model of osteoarthritis induced by monosodium iodoacetate. J Phys Ther Sci. 2017;29(4):590-7. https://doi.org/10.1589/jpts.29.590
  24. Jiang L, Li L, Geng C, Gong D, Jiang L, Ishikawa N, Kajima K, Zhong L. Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving ROS production and caspase activation in rat chondrocytes in vitro. J Orthop Res. 2013;31(3):364-9. https://doi.org/10.1002/jor.22250
  25. Gross A. BCL-2 family proteins as regulators of mitochondria metabolism. Biochim Biophys Acta. 2016;1857(8):1243-6. https://doi.org/10.1016/j.bbabio.2016.01.017
  26. Zhnag HD. Protective effect of diacerein on MIA-induced injury in rat osteoarthritis chondrocytes. Chongqing Medicine. 2016;45(8): 1019-1021.