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Healing Effect of Cordyceps Militaris Extract Complex on Collagen II-Induced Arthritis Rats

콜라겐 유도 관절염 동물 모델에 대한 동충하초 복합추출물의 치료 효과

  • Oh, Seung-Joon (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University) ;
  • Lee, Eun-Jung (Department of Korean Medicine Rehabilitation, College of Korean Medicine, Daejeon University)
  • 오승준 (대전대학교 한의과대학 한방재활의학교실) ;
  • 이은정 (대전대학교 한의과대학 한방재활의학교실)
  • Received : 2022.06.20
  • Accepted : 2022.07.05
  • Published : 2022.07.31

Abstract

Objectives This study was designed to evaluate the healing effect of Cordyceps Militaris (CM) on collagen II-induced arthritis rats. Methods Sprague-Dawley rats were randomly divided into 6 groups (normal, control, positive control, CM with low/medium/high dosage each). Type II collagen mixed with complete Freund's adjuvant (with 1:1 v/v) was injected subcutaneously, and the mixture was injected in a same manner one week after the first injection to boost arthritis. Arthritis index, paw thickness and von Frey test were conducted to observe physical changes. hematoxylin and eosin (H&E) staining was performed to observe knee cartilage. The levels of messenger RNA (mRNA) expressions of interleukin (IL)-1𝛽, IL-6, tumor necrosis factor-alpha (TNF-𝛼) in spleen were assessed by real-time polymerase chain reaction. Results Rheumatoid arthritis is an autoimmune disease that occurs on multiple joints and can lead to temporary shape change of bones or organ failure in severe cases. Here, we aimed to determine the effect of CM extract on rheumatoid arthritis by measuring paw thickness, arthritis index, conducting von Frey test and H&E staining, and evaluating the level of IL-1𝛽, IL-6, TNF-𝛼. As a result, paw thickness, arthritis index significantly decreased in low concentration group, hind leg became less sensitive in all expermental groups. Also, histological analysis showed that the damage of knee cartilage was prevented in all experimental groups. The level of mRNA of IL-1𝛽, IL-6, and TNF-𝛼 in spleen was analyzed to decide the effectiveness of CM extract. IL-1𝛽 did not show significant change, but IL-6 and TNF-𝛼 showed significant decrease in at least one of the experimental groups. Conclusions CM showed protective effect on knee tissue destruction and improved the physical conditions of the leg involving arthritis. Also, it showed that CM has anti-inflammatory effect on specific cytokines inducing rheumatoid arthritis. In conclusion, this study demonstrated that the therapeutic potential of CM for the treatment rheumatoid arthritis, and set the foundation for the further studies.

Keywords

References

  1. The Korean Orthiopaedic Association. Orthopaedics. 7th ed. Seoul:Choisin Medical Publishing Co. 2013.
  2. Obiri DD, Osafo N, Ayande PG, Antwi AO. Xylopia aethiopica (Annonaceae) fruit extract suppresses Freund's adjuvant-induced arthritis in Sprague-Dawley rats. J Ethnopharmacol. 2014;152(3):522-31. https://doi.org/10.1016/j.jep.2014.01.035
  3. Yoo DH. Recent trend in the treatment of rheumatoid arthritis. Journal of the Korean Orthopaedic Association. 2010;45(6):419-25. https://doi.org/10.4055/jkoa.2010.45.6.419
  4. Manheimer E, Wieland S, Kimbrough E, Cheng K, Berman BM. Evidence from the cochrane collaboration for traditional Chinese medicine therapies. J Altern Complement Med. 2009;15(9):1001-14. https://doi.org/10.1089/acm.2008.0414
  5. Hunt KJ, Coelho HF, Wider B, Perry R, Hung SK, Terry R, Ernst E. Complementary and alternative medicine use in England: results from a national survey. Int J Clin Pract. 2010;64(11):1496-502. https://doi.org/10.1111/j.1742-1241.2010.02484.x
  6. Goldrosen MH, Straus SE. Complementary and alternative medicine: assessing the evidence for immunological benefits. J Nat Rev Immunol. 2004;4(11):912-21. https://doi.org/10.1038/nri1486
  7. Healthcare Bigdata Hub. Yearly patients record [Internet] 2020 [cited 2020 May 9]. Available from: URL: http://opendata.hira.or.kr/op/opc/olapMfrnIntrsIlnsInfo.do.
  8. Kim KY, Sim KC, Kim GY, Choi CH, Jung JG, Chung JS, Jeong HW. Effects of acanthopanax senticosus and onion mixture extract on the collagen-induced arthritis in rat model. Korean J Oriental Physiology & Pathology. 2011;25(6):1000-7.
  9. Sim BY, Choi HJ. Effects of GamiBangkeehwangkee-tang ethanol extract on collagen-induced rheumatoid arthritis model of DBA/1 mice. The Korea Journal of Herbology. 2014;29:95-102. https://doi.org/10.6116/KJH.2014.29.6.95.
  10. Sim BY. Effect of Gamikyejakjimo-tang ethanol extract on rheumatoid arthritis factors. The Korea Journal of Herbology. 2014;29(5):65-73. https://doi.org/10.6116/KJH.2014.29.5.65
  11. The Compilation Committee of Korean Medicine dictionary. The Korean medicine dictionary. 2nd ed. Seoul:Jeongdam. 2010.
  12. Noh EM, Kim JS, Hur H, Park BH, Song EK, Han MK, Kwon KB, Yoo WH, Shim IK, Lee SJ, Youn HJ, Lee YR. Cordycepin inhibits IL-1beta-induced MMP-1 and MMP-3 expression in rheumatoid arthritis synovial fibroblasts. Rheumatology (Oxford). 2009;48(1):45-8. https://doi.org/10.1093/rheumatology/ken417
  13. Tan L, Song X, Ren Y, Wang M, Guo C, Guo D, Gu Y, Li Y, Cao Z, Deng Y. Anti-inflammatory effects of cordycepin: a review. Phytother Res. 2020;35(3):1284-97.
  14. Lee SY, Lee SJ, Hur SJ. Effects of Prunus mume Sieb. et Zucc. extract and its biopolymer encapsulation on a mouse model of colitis. J Sci Food Agric. 2017;97(2):686-92. https://doi.org/10.1002/jsfa.7790
  15. Lee HL, Park YS, Kim HJ, Lee AR, Choi JH, Pyee JH, Park HY, Kim JM. Extract from Prunus mume Sieb. et Zucc. fruit prevents LPS-induced homotypic aggregation of monocytic THP-1 cells via suppression of nitric oxide production and NF-κB activation. J of Life Science. 2015;25(7):801-9. https://doi.org/10.5352/JLS.2015.25.7.801
  16. Rho JH, Han CK. Effects of pork on feeding on detoxification process in rats intoxicated with lead. J Anim Sci & Technol. 2007;49(3):415-28. https://doi.org/10.5187/JAST.2007.49.3.415
  17. Harris ED. Rheumatoid arthritis. Pathophysiology and implications for therapy. N Engl J Med. 1990;322(18):1277-89. https://doi.org/10.1056/NEJM199005033221805
  18. Kwon YJ, Shung SJ, Kim TY, Park MC. Peroxisome proliferator-activated receptor-γ agonist inhibits pro-inflammatory gene expressions and cellular proliferation of fibroblast like synoviocytes from patients with rheumatoid arthritis by down-regulation of NF-kappaB. J Korean Rheum Assoc. 2010;17(2):153-61. https://doi.org/10.4078/jkra.2010.17.2.153
  19. Myers LK, Rosloniec EF, Cremer MA, Kang AH. Collagen-induced arthritis, an animal model of autoimmunity. Life Sci. 1997;61(19):1861-78. https://doi.org/10.1016/S0024-3205(97)00480-3
  20. Sylvester J, Liacini A, Li WQ, Dehnade F, Zafarullah M. Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-kappaB activities. Mol Pharmacol. 2001;59:1196-205. https://doi.org/10.1124/mol.59.5.1196
  21. Arend WP, Dayer JM. Inhibition of the production and effects of interleukin-1 and tumornecrosis factor alpha in rheumatoid arthritis. Arthritis Rheum. 1995;38:151-60. https://doi.org/10.1002/art.1780380202
  22. Scott DL, Wolfe F, Huizinga TWJ. Rheumatoid arthritis. Lancet. 2012;376(9746):1094-108. https://doi.org/10.1016/S0140-6736(10)60826-4
  23. Choi DY, Lee JD, Back YH, Lee SS, Yoo MC, Han CS, Yang HI, Park SD, Ryu MH, Park EK, Park DS. Recent trends of immunologic studies of herbal medicine on rheumatoid arthritis. The Journal of Korean Acupuncture & Moxibustion Society. 2004;21(4):177-96.
  24. The Society of Korean Medicine Rehabilitation. Korean rehabilitation medicine. 5th ed. Paju:Koonja Publishing. 2020:104-6.
  25. Won JY, Jeon CH, Song HJ, Jeong JW, Kim TK, Kim HH, Leem JT. The effect of orally administered herbal medicines in collagen, LPS, CFA induced rheumatoid like arthritis animal model: a systematic review of animal study articles published in Korea after 2008. J Korean Med Rehabil. 2007;27(4):33-53. https://doi.org/10.18325/JKMR.2017.27.4.33
  26. Lee HH, Lee S, Lee K, Shin YS, Kang H, Cho H. Anti-cancer effect of Cordyceps Militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis. Daru. 2015;23(1):35. https://doi.org/10.1186/s40199-015-0117-6
  27. Wang M, Meng XY, Yang RL, Qin T, Wang XY, Zhang KY, Fei CZ, Li Y, Hu Yl, Xue FQ. Cordyceps Militaris polysaccharides can enhance the immunity and antioxidation activity in immunosuppressed mice. Carbohydr Polym. 2012;89(2):461-6. https://doi.org/10.1016/j.carbpol.2012.03.029
  28. Rao YK, Fang SH, Wu WS, Tzeng YM. Constituents isolated from Cordyceps Militaris suppress enhanced inflammatory mediator's production and human cancer cell proliferation. J Ethnopharmacol. 2010;131(2):363-7. https://doi.org/10.1016/j.jep.2010.07.020
  29. Ahn TW, Lim SR, Wang SK. Effect of Kimchi containing Cordceps sinesis extract on the immune function of Babl/c mice. Kor J Oriental Preventive Medicine Society. 2002;6(2):156-67.
  30. Kim HJ, Kim D, Lee M, Jang A. Anti-inflammatory effect of dietary pork extract on proliferation and cytokine secretion using mouse primary splenocytes. Food Res Int. 2017;102:710-6. https://doi.org/10.1016/j.foodres.2017.09.058
  31. Andrews JS, Berger AE, Ware CF. Charaterization of the receptor for tumor necrosis factor (TNF) and lymphotoxin (LT) on human T lymphocytes. TNF and LT differ in their receptor binding properties and the induction of MHC class I proteins on a human CD4+ T cell hybridoma. J Immunol. 1990;144:2582-91. https://doi.org/10.4049/jimmunol.144.7.2582
  32. Freidin M, Bennett MV, Kessler JA. Cultured sympathetic neurons synthesize and release the cytokine interleukin-1 beta. Proc Natl Acad Sci USA. 1992;89:10440-3. https://doi.org/10.1073/pnas.89.21.10440
  33. Berek JS, Chung C, Watson JM, Knox RM, Martinez-Maza O. Serum interleukin-6 levels correlate with disease status in patients with epithelial ovarian cancer. Am J Obstet Gynecol. 1991;164:1038-42. https://doi.org/10.1016/0002-9378(91)90582-c
  34. Mateen S, Zafar A, Moin S, Khan AQ, Zubair S. Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta. 2016;455:161-71. https://doi.org/10.1016/j.cca.2016.02.010
  35. McInnes I, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Reviews Immunol. 2007;7:429-42. https://doi.org/10.1038/nri2094
  36. Dayer JM, Choy E. Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor. Rheumatology. 2010;49:15-24. https://doi.org/10.1093/rheumatology/kep329