• 동의생리병리학회지
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• 제23권5호
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• pp.1106-1115
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• 2009

Mori Ramulus has multiple applications in Korean traditional medicine prescription because it has antioxidant and anti-inflammatory effects by reducing macrophage activities. Yet, no studies on the anti-arthritic activity of EMR (extract of Mori Ramulus) have been reported in vitro and in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Because collagen-induced arthritis (CIA) is similar to RA in pathological symptoms and immune reactions, there have been several reports concerning RA using CIA mouse model. Here, we investigated the effects of Mori Ramulus on RA using CIA mice. The importance of CD4+ Th1 cells in RA progress was previously indicated and studies further showed that Th17 cells play a prime role in severity of disease. Accordingly, the present study was focused on CIA associated with CD4+ Th1 cells and Th1 7 cells. DBA/1OlaHsd mice were immunized with bovine type II collagen (CII). After a second collagen immunization, mice were treated with EMR once a day for 4 weeks. The severity of arthritis within the paw joints was evaluated by histological assessment of cartilage destruction and pannus formation. Immune cells in peripheral blood mononuclear cells (PBMC), draining lymph node (DLN) and paw joints, cytokine production and gene expression were assessed from CIA mouse using ELISA, FACS and real-time PCR analysis. Administration of EMR significantly suppressed the progression of CIA and inhibited the production of TNF-$\alpha$, IL-6 and IL-17 in the serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with EMR. In conclusion, our results demonstrate that EMR significantly suppressed the progression of CIA and that this action was mediated by the decreased production of TNF-$\alpha$, IL-6, IL-17 and collagen II-specific antibody in the serum. EMR suppressed Th17 cells and reduced level of IL-6 via B cell suppression, and thus, the levels of autoantibodies produced from B cells were decreased. Furthermore, EMR suppressed NKT cells which directly stimulate B cells and develop imbalance of Th1/Th2 cell. Oral administration of EMR (100 mg/kg or 200 mg/kg) significantly suppressed the progression of CIA, which is comparable to that of methotrexate (MTX, 0.3 mg/kg) used as a positive control. We are currently studying the mechanism underlying the therapeutic role for EMR in CIA mice.

• Journal of Yeungnam Medical Science
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• 제19권1호
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• pp.39-48
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• 2002

n-3 불포화지방산이 관절염의 발생 및 경과에 미치는 영향에 대해 알아보고자 Louvain종 흰쥐를 사용하여, 실험군을 정상군과 면역유도 (콜라겐+incomplete Freund's adjuvant)군으로 나누었고, 면역유도군은 다시 대조군 (정상식이) 및 n-3 다불포화지방산군 (식이에 5% n-3 다불포화지방산 함유) 으로 구분하여, 관절염 유도 1 주일전부터 n-3 다불포화지방산이 함유된 식이를 섭취시켰으며 관절염의 발생여부를 x-ray 소견과 광학현미경적 관찰을 통하여 확인하였다. 면역유도 5 주에 대조군의 38%에서 x-ray 소견상 족부종과 광학현미경상 염증소견이 발견되었으나 n-3 다불포화군에서는 이러한 변화가 없었다. 혈당과 혈장 인슐린은 면역유도나 n-3 다불포화지방산 투여에 의한 변화가 없었으나 혈장 중성지방과 콜레스테롤은 n-3 다불포화지방산투여에 의하여 감소하였다. n-3 다불포화지방산의 투여가 콜라젠에 의한 관절염의 발생을 예방 또는 치료할 수 있을 것으로 생각되며 이의 작용기전을 설명하기 위하여 후속 연구가 요망된다.

• 한국임상수의학회지
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• 제20권3호
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• pp.278-285
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• 2003

개에서 실험적으로 앞쪽 십자인대 중간부를 절단한 다음 초기 병변을 관찰하고 그 초기 병변에 대한 conjugated linoleic acid (CLA), carprofen 그리고 두 약물의 병용에 따른 효과를 비교하고자 본 실험이 수행되었다. 실험견은 앞쪽 십자인대를 파열한 CLA 처치군, Carprofen 처치군, CLA와 Carprofen 병용처치군 그리고 양성대조군과 파열하지 않은 정상견으로 구성된 음성대조군으로 총 5개군으로 분류하고 각 군에 5두씩 배치하였다. 실험견의 무릎관절 외측 피부를 절개하고 관절낭 외측을 절개한 다음 앞쪽 십자인대 중간부로 판단되는 부위를 절단하였다. Carprofen과 CLA는 수술 후 4주부터 4주 동안 경구 투여하였다 수술후 8주 후에 육안적, 조직학적 평가를 실시하였다. 조직학적 검사로는 hematoxylin and eosin 염색, standard toluidine blue, PAS 그리고 Masson trichrome 염색법을 이용하였으며 혈액학적, 그리고 방사선학적 검사를 실시하였다. 조직학적 검사와 혈액학적 검사에서 유의적인 변화는 나타나지 않았다. 방사선 검사에서는 앞쪽 십자인대 파열에 따른 대퇴골과 경골의 정렬이상과 부종이 모든 군에서 나타났으며 육안적 검사에서는 대부분 실험견의 대퇴 연골 표면상이 엷은 황색을 보였다. 이상의 결과를 통하여 실험적으로 유발된 개의 앞쪽 십자인대 파열에 대해 CLA, carprofen그리고 이들의 합제는 초기 변화상에서 뚜렷한 변화를 나타내지 않았다.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.168-172
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• 2003

Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

• Korean Journal of Acupuncture
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• 제26권2호
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• pp.27-38
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• 2009

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, principally characterized by synovial inflammation of the joints. We previously reported the effect of acupuncture for RA, but the mechanism is still unclear. Various factors such as oxidative stress and angiogenesis were involved in the pathogenesis of RA, and recently, it has also been reported that cytokines also play a major role in RA. Thus, we investigated whether acupuncture could induce any changes in the levels of cytokines including vascular endothelial growth factor (VEGF), angiogenin and epidermal growth factor (EGF) as well as erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and rheumatoid factor (RF) in the sera of RA patients. Methods: The forty three patients who met the American College of Rheumatology (ACR) criteria for RA recruited. The acupuncture group (n=21) underwent 14 sessions of partially individualized acupuncture treatment for 6 weeks, and the control group had no treatment (n=13) over the same periods. We evaluated ESR, CRP and RF. In addition, to find out the mechanism of acupuncture, we assessed the changes of the cytokine activities using protein cytokine array in the sera of the patients. Results: Acupuncture significantly decreased the levels of ESR and CRP, but RF were not changed after 6-week acupuncture treatments. Moreover, acupuncture reduced the levels of VEGF, angiogenin and EGF in the sera of the patients. Interestingly, they were related with angiogenesis, which is an important process in the pathogenesis of RA. The levels of oncostatin, interleukin(IL)-$1{\alpha}$, IL-8, leptin, monocyte chemotactic protein-1, macrophage-derived chemokine, macrophage inflammatory proteins-1, platelet-derived growth factor BB and RANTES were not changed significantly. Conclusions: The effect of acupuncture for reliving RA symptoms can be partially explained by inhibition of angiogenesis factors in the sera of the RA patients.

• 한국응용과학기술학회지
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• 제38권2호
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• pp.368-377
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• 2021

본 연구는 방사선 형질전환 차조기와 백출복합물(차조기 복합물)이 퇴행성관절염 관련 매개체에 미치는 영향을 확인하고자 MIA(monosodium iodoacetate)로 퇴행성관절염을 유도한 랫드로 평가하였다. 차조기 복합추출물을 2주 동안 25, 50, 100 mg/kg/day의 용량으로 경구 투여하고 랫드의 우측관절 내 공간에 MIA를 주입한 후 동일 용량을 4주 동안 지속 투여하였다. 이후, 혈청 바이오마커와 무릎 관절 분석의 형태학 및 조직병리학적 분석에 기초한 치료 효과를 평가하였다. 대조군 랫드와 비교하였을 때 차조기 복합추출물은 혈청 내 염증 및 골 대사 마커(TNF-α, MMP-3, COX-2, PGE₂, COMP, Aggrecan)의 생성량을 유의하게 감소시켰다. 이와는 반대로 연골 흡수 매개체인 CTX-2 생성을 증가시켰으며, 방사선 형질전환 차조기는 무릎 연골과 활막을 효과적으로 보존하였다. 그 결과, 차조기 복합물은 퇴행성관절염 증상을 개선하였다. 따라서, 차조기 복합물은 퇴행성관절염 관리를 위한 식품소재로 사용될 수 있다.