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Improvement Effect of the Eucommia ulmoides Extracts on CIA-induced Rheumatoid Arthritis Animal Models

두충 추출물의 류마티스관절염 동물모델에 대한 개선 효과

  • Ji, Joong-Gu (Department of Herbal Health & Pharmacy, Joongbu University)
  • 지중구 (중부대학교 한방보건제약학과)
  • Received : 2022.01.25
  • Accepted : 2022.02.24
  • Published : 2022.02.28

Abstract

The present study aimed to evaluate the effect of Eucommia ulmoides extracts on rheumatoid arthritis biomarker in a CIA-induced DBA/1 mice. For evaluation, Eucommia ulmoides extracts was administered orally at dose of 100 mg/kg/day for 4 weeks after production of an animal model of rheumatoid arthritis and we confirmed the treatments' effects based on serum biomarker, radiological, structural parameter analysis. Compared to the negative control group, the Eucommia ulmoides extracts treatments significantly reduced the serum level of inflammation and immunoglobulin markers (i.e., TNF-α, IgG, and hs-CRP), and significantly decreased the monocyte count of white blood cells. Furthermore, the Eucommia ulmoides extracts treatments effectively preserved the joint destruction, and little the joint deformation. Moreover, compared to the negative control group, the Eucommia ulmoides extracts treatments increased the bone volume, and significantly decreased bone inflammation. The results indicate that the Eucommia ulmoides extracts improved rhrumatoid arthritis symptoms. Thus, the Eucommia ulmoides extracts may be a novel therapeutic option for the management of rheumatoid arthritis.

본 연구는 CIA에 의해 유발된 DBA/1 마우스를 통해 류마티스관절염 바이오마커에 대한 두충 추출물의 효과를 평가하였다. 평가를 위해 류마티스관절염 동물모델 제작 후 100 mg/kg/day로 4주간 경구 투여하고 혈청 바이오마커, 방사선, 구조적 매개변수 분석을 통해 치료 효과를 확인하였다. 음성대조군과 비교하여, 두충 추출물은 염증 및 면역글로불린 마커(TNF-α, IgG 및 hs-CRP)의 생성을 유의하게 감소시켰고, 백혈구의 단핵구 수를 유의적으로 감소시켰다. 또한, 두충 추출물은 관절 파괴를 효과적으로 보존하고 관절 변형을 줄였으며, 골 밀도의 증가와 유의적으로 골 염증을 감소시켰다. 이러한 결과는 두충 추출물이 류마티스관절염 증상을 개선하는 것을 나타낸다. 따라서, 두충 추출물은 류마티스관절염 관리를 위한 새로운 치료 옵션이 될 수 있음을 보여준다.

Keywords

References

  1. S. Bae, I. Hong, O. H. Cho, "Influence of Anxiety, Depression and Self-Esteem on Quality of Life in Patients with Rheumatoid Arthritis". Journal of Korean Academy of Fundamentals of Nursing, Vol.28, No.2, pp. 165-173, (2021). https://doi.org/10.7739/jkafn.2021.28.2.165
  2. A. Besirli, J. O. Alptekin, D. Kaymak, O. A. Ozer, "The relationship between anxiety, depression, suicidal ideation and quality of life in patients with rheumatoid arthritis". Psychiatric quarterly, Vol.91, No.1, pp. 53-64, (2020). https://doi.org/10.1007/s11126-019-09680-x
  3. I. B. McInnes, G. Schett, "The pathogenesis of rheumatoid arthritis". New England Journal of Medicine, Vol.365, No.23, pp. 2205-2219, (2011). https://doi.org/10.7748/phc2011.11.21.9.29.c8797
  4. Y. K. Sung, "Advantages and disadvantages of targeted therapy in patients with rheumatoid arthritis". Journal of the Korean Medical Association/Taehan Uisa Hyophoe Chi, Vol.64, No.2. pp. 90-93, (2021). https://doi.org/10.5124/jkma.2021.64.2.90
  5. D. E. Furst, P. Emery, "Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets". Rheumatology, Vol.53, No.9, pp. 1560-1569, (2014). https://doi.org/10.1093/rheumatology/ket414
  6. K. W. Kim, S. H. Lee, M. L. Cho, H. J. Oh, Y. J. Woo, S. H. Kim, H. R. Kim,. "IL-17 and Toll-like Receptor 2 or Toll-like Receptor 4 Combined Engagement Upregulates RANKL and IL-6 in Human Rheumatoid Synovial Fibroblasts", The Journal of the Korean Rheumatism Association, Vol.17, No.1, pp. 36-45, (2010). https://doi.org/10.4078/jkra.2010.17.1.36
  7. S. S. Seong, C. B. Choi, J. H. Woo, K. W. Bae, C. L. Joung, W. S. Uhm, T. H. Kim, J. B. Jun, D. H. Yoo, J. T. Lee, S. C. Bae,"Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA itself and of tumor necrosis factor blockers". The Journal of rheumatology, Vol.34, No.4, pp. 706-711, (2007).
  8. Ahn, DK. Illustrated guide to clinical medical herbs. pp.261-262, Hyeonamsa Publishers, (2012).
  9. Y. H. Kim, H. Park, "Study on the anti-inflammatory activity and mechanism of medicinal plants used in the treatment of arthritis". Korean Journal of Clinical Laboratory Science, Vol.48, No.3, pp. 176-182, (2016). https://doi.org/10.15324/kjcls.2016.48.3.176
  10. Y. J. Kim, W. Heo, H. S. Choi, K. S. Kang, G. S. Hwang, J. Y. Baek, B. A. Koo, H. Y. Kim, "Anti-inflammatory Effect of Eucommia Ulmoides Oliver Bark Extract on P. gingivalis LPS-induced YD-38 Cells". Korean Journal of Pharmacognosy, Vol.50, No.3, pp. 185-190, (2019).
  11. X. He, J. Wang, M. Li, D. Hao, Y. Yang, C. Zhang, R. He, R. Tao, "Eucommia ulmoides Oliv.: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine". Journal of Ethnopharmacology, Vol.151, No.1, pp. 78-92, (2014). https://doi.org/10.1016/j.jep.2013.11.023
  12. J. Lin, Y. J. Fan, C. Mehl, J. J. Zhu, H. Chen, L. Y. Jin, J. H. Xu, H. M. Wang, "Eucommia ulmoides Oliv. antagonizes H 2 O 2-induced rat osteoblastic MC3T3-E1 apoptosis by inhibiting expressions of caspases 3, 6, 7, and 9". Journal of Zhejiang University Science B, Vol.12, No.1, pp. 47-54, (2011). https://doi.org/10.1631/jzus.B1000057
  13. R. Zhang, Y. L. Pan, S. J. Hu, X. H. Kong, W. Juan, Q. B. Mei, "Effects of total lignans from Eucommia ulmoides barks prevent bone loss in vivo and in vitro". Journal of ethnopharmacology, Vol.155, No.1, pp. 104-112, (2014). https://doi.org/10.1016/j.jep.2014.04.031
  14. J. Y. Kim, J. I. Lee, M. K. Song, D. Lee, J. Song, S. Y. Kim, J. Park, H. Y. Choi, H. Kim, "Effects of Eucommia ulmoides extract on longitudinal bone growth rate in adolescent female rats". Phytotherapy Research, Vol.29, No.1, pp. 148-153, (2015). https://doi.org/10.1002/ptr.5195
  15. D. H. Choi, S. J. Lee, H. C. Jeong, K. M. Kim, M. Y. Kwon, S. Lee, "Anti-osteoarthritis and anti-arthrodynia effects of a mixture of fermented achyranthes japonica Nakai, Angelica gigas Nakai, and Eucommia ulmoides Oliver extracts on monosodium iodoacetate-induced arthritis in rats". Journal of the Korean Society of Food Science and Nutrition, Vol.48, No.11, pp. 1179-1185, (2019). https://doi.org/10.3746/jkfn.2019.48.11.1179
  16. J. M. Kim, H. Y. Kim, "Pathogenesis of rheumatoid arthritis". Journal of the Korean Medical Association, Vol.53, No.10, pp. 853-861, (2010). https://doi.org/10.5124/jkma.2010.53.10.853
  17. M. L. Cho, C. H. Yoon, S. Y. Hwang, M. K. Park, S. Y. Min, S. H. Lee, S. H. Park, H. Y. Kim, "Effector function of type II collagen-stimulated T cells from rheumatoid arthritis patients: Cross-talk between T cells and synovial fibroblasts". Arthritis & Rheumatism, Vol.50, No.3, pp. 776-784, (2004). https://doi.org/10.1002/art.20106
  18. D. J. Min, M. L. Cho, S. H. Lee, S. Y. Min, W. U. Kim, J. K. Min, S. H. Park, C. S. Cho, H. Y. Kim, "Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts". Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, Vol.50, No.4, pp. 1146-1155, (2004).
  19. P. F. Zangerle, D. De. Groote, M. Lopez, R. J. Meuleman, Y. Vrindts, F. Fauchet, I. Dehart, M. Jadoul, D. Radoux, P. Franchimont, "Direct stimulation of cytokines (IL-1β, TNF-α, IL-6, IL-2, IFN-γ and GM-CSF) in whole blood: II". Application to rheumatoid arthritis and osteoarthritis. Cytokine, Vol.4, No.6, pp. 568-575, (1992). https://doi.org/10.1016/1043-4666(92)90021-I
  20. H. Shen, J. C. Goodall, J. S. Hill Gaston, "Frequency and phenotype of peripheral blood Th17 cells in ankylosing spondylitis and rheumatoid arthritis". Arthritis & Rheumatism: Official Journal of the American College of Rheumatology, Vol.60, No.6, pp. 1647-1656, (2009).
  21. J. Leipe, M. Grunke, C. Dechant, C. Reindl, U. Kerzendorf, H. Schulze-Koops, A. Skapenko, "Role of Th17 cells in human autoimmune arthritis". Arthritis & Rheumatism, Vol.62, No.10, pp. 2876-2885, (2010). https://doi.org/10.1002/art.27622
  22. Y. H. Kim, H. Park, "Study on the anti-inflammatory activity and mechanism of medicinal plants used in the treatment of arthritis". Korean Journal of Clinical Laboratory Science, Vol.48, No.3, pp. 176-182, (2016). https://doi.org/10.15324/kjcls.2016.48.3.176
  23. B. K. Lee, Y. C. Lee, J. C. Lee, "Inhibitory Effect of a Decoction of Eucommiae ulmides OLIVER and Dipsacus asperoides CY Cheng et TM Ai on Collagen II-induced Arthritis Mice". The Korea Journal of Herbology, Vol.25, No.1, pp. 55-63, (2010). https://doi.org/10.6116/KJH.2010.25.1.055
  24. W. P. Arend, J. M. Dayer, "Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis". Arthritis and rheumatism, Vol.38, No.2, pp. 151-160, (1995). https://doi.org/10.1002/art.1780380202
  25. H. J. Yeo, J. H. Lee, H. J. Lee, K. S. Byun, H. J. Im, M. J. Kim, "Microvascular Findings in Patients with Rheumatoid Arthritis-Assessed, Using Fundus Photography and Fluorescein Angiography". Journal of Rheumatic Diseases, Vol.20, No.4, pp. 231-237, (2013). https://doi.org/10.4078/jrd.2013.20.4.231
  26. J. K. Jung, K. H. Son, Y. S. Kim, Y. K. Park, "Effect of Citri Pericarpium ethanol extract on collagen-induced arthritis in mice". The Korea Journal of Herbology, Vol.26, No.3, pp. 1-6, (2011). https://doi.org/10.6116/KJH.2011.26.3.001
  27. B. Y. Sim, H. J. Choi, J. W. Bak, D. H. Kim, "Effects of GamiBangkeehwangkee-tang (fangjihuangqi-tang) ethanol extract on Collagen-induced Rheumatoid Arthritis model of DBA/1 mice". The Korea Journal of Herbology, Vol.29, No.6, pp. 95-102, (2014). https://doi.org/10.6116/KJH.2014.29.6.95.