• Journal of Acupuncture Research
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• v.28 no.1
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• pp.37-44
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• 2011

배경 및 목적 : 봉독약침요법(bee venom pharmacopuncture, BVP)은 rheumatoid arthritis(RA)의 치료에 활용되고 있으나, RA로 인한 염증성 통증에 대한 봉독약침의 진통효과와 specific mechanism은 아직까지 명확하게 밝혀지지 않았다. 이에 본 연구에서는 RA animal model로서 collagen-induced arthritis(CIA) rat model에서 봉독약침의 a1-adrenergic, 5HT-3 그리고 muscarinic cholinergic mechanism을 확인하고자 한다. 방법 : CIA를 유도하기 위하여 male Sprague-Dawley rat에 freund's incomplete adjuvant에 유화(乳化)시킨 bovine type II collagen을 주입하고 14일 후 booster injection 시행하였다. 진통효과는 tail flick latency (TFL)로 평가하였다. 결과 : 관절염의 유도 이후 염증성 통증 역치는 시간이 지나면서 낮아지며, 5주 이후로는 통증 역치에 큰 변화가 없이 유지되었다. 첫 번째 immunization으로부터 5주 경과 후 족삼리($ST_{36}$)에 봉독약침처치(0.25 mg/ kg)를 시행하여 유의한 진통효과를 관찰하였다. 또한 봉독약침의 진통효과는 ondansetron(5HT-3 receptor antagonist, 0.5mg/kg, i.p.), atropine(muscarinic cholinergic receptor antagonist, 1mg/kg, i.p.)의 전처치에 의하여 억제되었으나, prazosin(a1-adrenergic receptor antagonist, 1mg/kg, i.p.)의 전처치에 의해서는 억제되지 않았다. 결론 : 봉독약침은 CIA로 인한 염증성 통증에 유의한 진통효과를 나타내며 그 analgesic mechanism은 5HT-3와 muscarinic cholinergic receptor에 의하여 매개되며 a1-adrenergic receptor에 의하여 매개되지는 않았다.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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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.

• Korean Journal of Plant Resources
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• v.21 no.4
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• pp.336-340
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• 2008

Corilagin (CRN) isolated from Euphorbia helioscopia as rheumatoid arthritis drug. CRN was medicated to the abdominal cavity of collagen induced arthritis (CIA) mice that was an animal model for rheumatoid arthritis and its effects on incidence and arthritis index were studied. The results were as folllows; It was exhibited that medicating corilagin inhibited the infiltration of activated T lymphocytes into an inflammatory joint. The production of IgG and IgM that were RF (rheumatoid factor) and inflammatory cytokine, IL-6 and $TNF-{\alpha}$were reduced. After measuring $IFN-{\gamma}$and IL-4, it was found that it was shifted into Th2 immune response as increasing in IL-4. After liver function test, studies on liver poisoning of AST/ALT should be continued.

• The Journal of Korean Obstetrics and Gynecology
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• v.22 no.2
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• pp.1-25
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• 2009

Purpose: The purpose of this study is to investigate the anti-arthritis effects of Jeonsaenghwalhyeoltanggamibang(JHTG) on collagen-induced arthritis(CIA) in mice. Methods: To assess the effects of JHTG on CIA in mice, we conducted several experiments such as analysis of arthritis index, cell count of draining lymph node(DLN) and paw joint, measurement of serum antibody levels and observation of the histological changes of joint. Results: 1. JHTG extract had a suppressive effect on the arthritis index of paw joints in CIA mice. 2. JHTG extract increased the total cell number of DLN, and decreased the total cell number of paw joints in CIA mice. 3. JHTG extract increased the absolute number of various cell surface receptors in DLN, and decreased the absolute number of B220+/CD23+ cells in DLN in CIA mice. 4. JHTG extract decreased the absolute number of CD3+, CD4+, CD11b+/Gr-1 cells in paw joint in CIA mice. 5. JHTG extract didn't decrease the absolute number of CD4+/CD25+ cells in paw joints in CIA mice. 6. JHTG extract decreased levels of total IgM in the serum of CIA mice, but had no effect on levels of collagen II specific antibody. 7. JHTG extract decreased the destruction of articular cartilages and collagen fibers and the proliferation of synovial cells in paw joints from CIA mice. Conclusion: These results indicate that JHTG has clinical potential for the treatment of rheumatoid arthritis by modulating the immune response.

• Journal of Yeungnam Medical Science
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• v.40 no.1
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• pp.23-29
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• 2023

The pathological hallmark of rheumatoid arthritis (RA) is a synovial pannus that comprises proliferating and invasive fibroblast-like synoviocytes, infiltrating inflammatory cells, and an associated neoangiogenic response. Animal models have been established to study these pathological features of human RA. Spontaneous and induced animal models of RA primarily reflect inflammatory aspects of the disease. Among various induced animal models, collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models are widely used to study the pathogenesis of RA. Improved transplantation techniques for severe combined immunodeficiency (SCID) mouse models of RA can be used to evaluate the effectiveness of potential therapeutics in human tissues and cells. This review provides basic information on various animal models of RA, including CIA and CAIA. In addition, we describe a SCID mouse coimplantation model that can measure the long-distance migration of human RA synoviocytes and cartilage destruction induced by these cells.

• Journal of Korean Medicine Rehabilitation
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• v.18 no.2
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• pp.1-15
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• 2008

Objectives : The aim of this study was to know the immunity response of Haedongpibokhap-bang($H{\check{a}}it{\acute{o}}ngp{\acute{i}}f{\grave{u}}h{\acute{e}}-f{\bar{a}}ng$) to rheumatoid arthritis in collagen-induced arthritis(CIA) mice. Methods : For this purpose, Haedongpibokhap-bang($H{\check{a}}it{\acute{o}}ngp{\acute{i}}f{\grave{u}}h{\acute{e}}-f{\bar{a}}ng$) was orally administerd to mice with arthritis induced by collagen II and then value of immunocyte in spleen, draining lymph node and paw joint and cytokine(IL-6, $TNF-{\alpha}$), rheumatoid factor (IgG and IgM) in serum were measured. Results : 1. The arthritis index was significantly decreased. 2. In total cell counts of spleen, DLN and paw joint, the cells in spleen decreased while there was a significant increase in DLN and significant decrease in paw joint. 3. In lymph nodes, CD3+, CD3+/CD69+, CD4+, CD8+ cells increased significantly. 4. In joints, CD3+ and CD11+b/Gr-1+ cells decreased significantly. 5. Serum IL-6 and $TNF-{\alpha}$ were decreased significantly. 6. Production of serum IgG and IgM decreased significantly. Conclusions : The results present that Haedongpibokhap-bang($H{\check{a}}it{\acute{o}}ngp{\acute{i}}f{\grave{u}}h{\acute{e}}-f{\bar{a}}ng$) controls abnormal activity of immune system, inhibitig collagen-induced arthritis(CIA).

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.27-40
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• 2000

The influence of moxibustion, a traditional Chinese medical treatment, on type II collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type II collagen (C Il). The main incidence of arthritis started about on day 30 and lasted to day 60 after the first immunization. Moxibustion with three different regimens, was applied at the acupoint equivalent to GV 4 every other day. Moxibustion, from day 0 to day 30 after the first immunization, suppressed the onset and development of arthritis, as well as anti-collagen antibody level. Treatment with moxibustion, from the day 31 to day 60, also resulted in a significant inhibition of progression of arthritis and production of anti-C II antibody. Thirdly we examined the influence of moxibustion on the established arthritis. Moxibustion given from day 61 to day 120, significantly but mildly decreased the anti-C II antibody level in diseased mice, while the bone erosion and joint destruction were not affected. These results indicate that moxibustion could prevent the incidence and attenuates the development of murine CIA.

• The Journal of Korean Medicine
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• v.31 no.2
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• pp.19-35
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• 2010

Objectives: This study was carried out to find the effects of Changchuldoin-tanggamibang (hereinafter referred to CDIT) on the inhibition of arthritis induced by collagen on DBA/1J mouse. Methods: The experimental mice were divided into four groups: normal group (Nr), control group (CIA-CT), methotrexate group (CIA-MTX), and Changchuldoin-tanggamibang group (CIA-CDIT). Cytotoxicity, hepatotoxicity, arthritis index, value of immunocytes in draining lymph node and paw joint, and rheumatoid factor (IgG, IgM) in serum were measured in vivo. Results: 1. Cytotoxicity against hFCs was not shown in any concentration. 2. Hepatotoxicity was low in the CDIT-treated group compared with the MTX group. 3. The arthritis index decreased significantly. 4. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 5. In lymph nodes, CD19+, CD3+, CD4+, CD8+, CD3+/CD8+, CD3+/CD69+, CD4+/CD25+, CD3+/CD49b+, and CD4+/CD44+ cells increased significantly, while B220+/CD23+, and CD11c+/MHCII+ cells decreased significantly. 6. In joints, CD3+, CD4+, CD4+/CD25+, and CD11b+/Gr-1+ cells decreased significantly. 7. The level of IgG decreased and the level of IgM significantly decreased compared with the control. 8. Anti-collagen II in serum decreased compared with the control. 9. Around the joint of the CDIT group, infiltration of inflammation, synovial hyperplasia, invasion of cytokine, of cartilage, deposition of collagen and synovial injury decreased compared with the control in histopathologic observation (HE, MT staining). Conclusions: Comparison of the results for this study showed that CDIT had immunomodulatory effects. We expect that CDIT could be used as a effective drug for not only rheumatoid arthritis but also another auto-immune diseases. Therefore, we have to survey continuously, looking for effective substances and mechanisms in the future.

• Journal of Nutrition and Health
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• v.45 no.5
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• pp.437-442
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• 2012

The purpose of this study was is to investigate the arthritis treatment and prevention of the effects the herbral administration to experimental animals induces arthritis 4 weeks for medicinal herbs (Scutellaria baicalensis Georgi, Acanthopanacis cortex, Achyranthis Radix). To investigate the prevention of histopathological examination and molecular biological examinations for arthritis improvement in vivo New Zealand, white rabbits were divided into a normal (Normal, n = 7), or a collagen-induced arthritis (CIA, n = 7), or a collagenase injection and medicinal herbs (SAA, n = 7). It was confirmed that induced arthritis was treated with Gross examination, and the measurement of average arthritis index (MAI) and improved arthritis by medicinal herbs. TNF-${\alpha}$ and IL-$1{\beta}$ were significantly increased in the CIA and SAA groups, compared to the normal group (p < 0.05). MMP-1 and TIMP-2 were significantly increased in the CIA, compared to the other groups (p < 0.05). MMP-1 and TIMP-2 were significantly decreased in the SAA group, compared to the CIA group (p < 0.05). As a result, Herbal administration used in this study might be able to help in the treatment of arthritis induced by inflammatory and immunosuppressive effects, that which can be expected.

• BMB Reports
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• v.49 no.6
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• pp.331-336
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• 2016

In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouseI-A^q in a murine CIA model. We found that recombinant I-A^q/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-A^q/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis.