• 한국약용작물학회지
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• 제28권6호
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• pp.471-480
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• 2020

Background: The roots of Cirsium japonicum var. ussuriense (RCJ) have been used as traditional medicine in Korea for hematuria and hematemesis. These extracts exert anti-oxidative and anti-inflammatory effects by scavenging for free radical and regulating the inflammatory response. However, the effect of RCJ on rheumatoid arthritis (RA) has not been elucidated. Thus, we evaluated the water extract of RCJ (WRCJ) using type II collagen-induced RA models. Methods and Results: RA was induced by immunization with type II collagen. All experimental materials were orally administered daily for three weeks. The positive control group was administered with 0.2 mg/kg methotrexate (n = 7), while the experimental group was administered with WRCJ (100 or 500 mg/kg, n = 7). Serum levels of TNF-alpha, Interleukin 6 (IL-6), and type II collagen IgG (CII) were measured using ELISA. Administration of 500 mg/kg WRCJ decreased the levels of TNF-alpha, IL-6, and CII. Moreover, WRCJ treatment diminished swelling of hind legs and infiltration of inflammatory cells in RA models' synovial membrane. Conclusions: These results indicate that WRCJ could improve RA, reduce inflammatory indicators and synovial inflammation. However, further experiments are required to determine how WRCJ can influence the signal transduction pathway in RA.

• Journal of Acupuncture Research
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• 제18권4호
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• pp.125-142
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• 2001

Objective : The purpose of this study is to observe the effect of Aqua-acupuncture with Stephania Tetrandra Solution (ST-AS) on arthritis. Methods : The author performde several experimental items : that isgene expression and secretion of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, MMP-2, production of ROS, paw thickness, DTH, weight of spleen, expression of CD4+, CD8+, CD19+ in the spleen, production of IL-6, TNF-${\alpha}$, examination of histology. Results : The obstain results are summarized as follows. 1. IL-$1{\beta}$, IL-6, TNF-${\alpha}$ gene expression of hFLS were significantly inhibited in treatmentgroup, and gene expression of MMP-2 was not inhibited in treatmentgroup. 2. The secretion amount of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ were significantly inhibited in treatmentgroup. 3. Expression of P-38 MAP kinase and production of ROS were inhibited in treatmentgroup. 4. Treatmentgroup were significantly inhibited the incidence of arthritis, hind paw edema, the index of arthritis and DTH of CIA (collagen II-induced arthritis) mice. 5. Treatmentgroup were significantly decreased splenetic weight and the number of CD4+, CD8+, CD19+ activated cells and secretion aroout of IL-6, TNF-${\alpha}$ of CIA (collagen II-induced arthritis) mice.. 6. Treatmentgroup were expressed form of new bone, synoviumin, new margine in histology imperison to controlgroup. Conclusions : Taking all these observations into account, ST-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.

• 대한본초학회지
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• 제25권4호
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• pp.137-143
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• 2010

Objectives : The present study was conducted to examine the effect of Cudraniae Tricuspidatae Radix(CTR), which is the radix part of Cudrania tricuspidata Bureau, on cytokine secretion from the joint cells and spleen cells of mice with arthritis induced by collagen and verify its efficacy against rheumatoid arthritis. Methods : Three kinds of extract were prepared from CTR through extraction with hot-water and ethanol. The levels of cytokine secreted from the cells were measured, after the mice knee joint cells were cultured with each extract. Results : The three kinds of extracts from CTR decreased the growth rate and levels of inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ from knee joint cells of mice. All of the organic-soluble fraction, such as hexane, ethyl ether, ethyl acetate, butanol, and residual water-soluble fraction decreased the levels of IL-$1{\beta}$, TNF-${\alpha}$, IL-6, and IL-10. Conclusion : These results suggest that CTR had some effects on rheumatitis, with fat and water-solubles in organic solvent considered as the effective element.

• Reproductive and Developmental Biology
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• 제35권2호
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• pp.143-149
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• 2011

Arthritis is a common disease in aged people, and is clinically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Although common symptoms such as pain are present, the underlying pathological mechanisms are slightly different. Therefore, the objectives of the present study were to compare joint damage induced by RA and OA by analyzing the major morphological and molecular differences, and to propose a suitable therapeutic intervention based on the pathophysiological conditions of bones and joints. For the RA animal model, 8-week-old DBA1/J mice were immunized with bovine type II collagen emulsified in complete Freund's adjuvant (CFA). Normal C57BL/6 mice (over 2 years of age) were used for OA. The clinical arthritis score was calculated using a subjective scoring system, and paw thicknesses were measured using calipers. The serum TNF ${\alpha}$ level was analyzed using an ELISA kit. Micro-CT was used to identify pathological characteristics and morphological changes. In collagen-induced RA mice, there were increased ankle joint volumes and clinical scores (p<0.01). The concentration of TNF ${\alpha}$ was significantly increased from 3 to 7 weeks after immunization. Micro-CT images showed trabecular bone destruction, pannus formation, and subchondral region destruction in RA mice. OA among aged mice showed narrowed joint spaces and breakdown of articular cartilage. This study suggests that a careful therapeutic intervention between RA and OA is required, and it should be based on morphological alteration of bone and joint.

• IMMUNE NETWORK
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• 제21권6호
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• pp.45.1-45.13
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• 2021

Many mouse models of rheumatoid arthritis have been identified, but only a limited number are present for axial spondyloarthritis (AxSpA). Collagen Ab-induced arthritis (CAIA) is one of the most widely used mouse models of arthritis, and it is complement-dependent. We found that mice developing CAIA also developed spinal lesions similar to those found in AxSpA. To induce CAIA, mice were injected intraperitoneally at day 0 with anti-collagen Abs, followed by LPS injection at day 3. CAIA mice demonstrated a significant kyphosis through the spine, as well as hypertrophic cartilage and osseous damage of the intravertebral joints. Immunohistochemical staining of the kyphotic area revealed increased complement C3 deposition and macrophage infiltration, with localization to the intravertebral joint margins. Near Infrared (NIR) in vivo imaging showed that anti-collagen Abs conjugated with IRDye^® 800CW not only localized to cartilage surface in the joints but also to the spine in arthritic mice. We report here a novel preclinical mouse model in which, associated with the induction of CAIA, mice also exhibited salient features of AxSpA; this new experimental model of AxSpA may allow investigators to shed light on the local causal mechanisms of AxSpA bone and soft tissue changes as well as treatment.

• Biomolecules & Therapeutics
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• 제23권2호
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• pp.195-200
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• 2015

We tested the hypothesis that micro-computed tomography (micro-CT) analysis provides a better quantitative readout of the therapeutic potential of methotrexate (MTX) for treating collagen-induced arthritis (CIA) in rats and compared to conventional histopathological examination. Rats were divided into three groups: Group 1 (G1) was treated with 0.9% saline, whereas groups 2 (G2) and 3 (G3) were boosted with type II collagen at days 0 and 7. Following the first collagen immunization, rats in G1 and G2 were treated with 0.9% saline and those in G3 were treated with 1.5 mg/kg MTX from day 14 to 28. All rats were sacrificed on day 28, at which point and all hind knee joints were analyzed by micro-CT and histopathological examination. Micro-CT analyses showed that bone volume and trabecular number were significantly decreased in G2 and G3 compared to G1 (p<0.01), as was percent bone volume (p<0.05 and p<0.01, respectively). However, bone surface/bone volume was significantly increased in G2 and G3 compared to G1 (p<0.05 and p<0.01, respectively). Trabecular separation was significantly increased in G3 compared to G1 (p<0.05). Histopathological examination showed that knee joints of rats in G2 and G3 showed severe joint destruction with inflammatory cell infiltration. However, cartilage destruction was slightly reduced in G3 compared to G2. Taken together, these results suggest that MTX treatment reduced cartilage destruction in rats with CIA, and micro-CT analyses made it possible to quantify arthritic bony lesion.

• Journal of Acupuncture Research
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• 제19권6호
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• pp.155-170
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• 2002

면역억제와 면역항진의 작용을 지닌 녹용(鹿茸)약침의 실험쥐에서의 type II collagen(CII)으로 유발된 관절염(CIA)에 대한 효과를 연구하였다. 본 실험에서 녹용(鹿茸)약침군과 생리식염수군을 대조군으로 하여 실험쥐에게 약침시술을 하였다. 녹용(鹿茸)약침이 CII에 작용하는 세포반응에 대한 효과를 검정하였는데, 대조군에서는 CII 유발주사 후 24일에 관절염이 관찰되었고, CIA의 정도가 점차적으로 심해졌다. 생리식염수 처리군과 비교해 24일 동안 하루에 한번 $50{\mu}g/kg$ 이상 용량의 녹용(鹿茸)약침은 CII 처리 T cell의 interleukin 2(IL-2)와 interferon-${\gamma}$($IFN-{\gamma}$) 생산능력을 억제했다. 또한 녹용(鹿茸)약침은 CII처리 임파절과 대식세포의 tumor necrosis facter ${\alpha}$($TNF-{\alpha}$)의 생산을 억제했다. 한편 CIA에 대한 약침효능의 지표는 녹용(鹿茸)약침을 14일간 하루에 한번씩 처리하면서, 소의 CII로 3주 간격으로 2번 유발접종을 실시하여 검정하였다. 첫 CII 유발접종과 동시에 일일 투여량 $100{\mu}g/kg$으로 14일간의 녹용(鹿茸)약침이 항체형성과 CII에 대한 지연형 과민성 뿐만 아니라 관절염의 증가도 막아주었다. 녹용(鹿茸)약침을 관절염 유발성 CII의 2차 접종과 동시에 시술한 결과, 관절염과 CII에 대한 면역반응을 억제하였다. 이에 저자는 CII로 유발된 관절염에 대한 녹용(鹿茸)약침의 억제효과에 대하여 보고하는 바이다.

• Korean Journal of Acupuncture
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• 제22권2호
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• pp.89-105
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• 2005

Objective & Methods : This study is performed to observe the effect of Herbal-acupuncture with Notopterygii Radix Herbal-Acupuncture Solution(NR-HAS) at Joksamni(ST36) on Collagen II-induced arthritis (CIA) in DBA/1J mice. Result : 1. The highest survival rate of mice lung fibroblasts were measured in the 1% NR-HAS, and the expression of $TNF-{\alpha}$ in synovial cells were significantly decreased in the 1% and 10% NR-HAS. 2. The incidence of arthritis and the spleen weight were significantly decreased by Notopterygii Radix Herbal-acupuncture(NR-HA) at ST36. 3. The levels of IL-6, $INF-{\gamma},\;TNF-{\alpha}$, IgG, IgM, anti-collagen II in serum of CIA mice were significantly decreased by NR-HA at ST36. 4. In histology, the cartilage destruction and synovial cell proliferation were decreased by NR-HA at ST36, and the collagen fiber expressions in the NR-HA I II groups were similar with that of the normal group. 5. In lymph node, the expression ratios of $CD3e^+\;to\;CD19^+$ cell and $CD4^+\;to\;CD8^+$ cell in the NR-HA I II groups were similarly maintained as those in the normal group. 6. In lymph node, $CD69^+/CD3e^+$ cells and $CD11a^+/CD19^+$ cells were decreased by NR-HA at ST36. 7. In the articular joint, $CD11b^+/Gr-1^+$ cells were decreased by NR-HA at ST36. 8. NR-HA at ST36 did not make a considerable difference in DBA/1J mice without CIA 9. Throughout the overall experimental result, NR-HA I group showed more predominant effect than the NR-HA II group. Conclusion : These results suggest that NR-HA at ST36 has an effect to control synovial cell proliferation and cartilage destruction in rheumatoid arthritis, as well as prophylaxis is important to treat rheumatoid arthritis in clinic.

• 동의생리병리학회지
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• 제18권1호
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• pp.122-136
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• 2004

To evaluate effect of CRSST on inhibiting the occurrence of arthritis, we performed the experiments including production of inflammatory cytokine and immunoglobin in collagen induced arthritis model. The results were obtained as follows. CRSST extract shows any cytotoxicity effect on mouse lung fibroblast cells at dose of 400 ㎍/㎖. CRSST group shows inhibitory effect on arthritis incidence than control group for six weeks. Arthritis index of CRSST group reduces from 4 weeks (75±17.4%) to 6 weeks (33.3±10.0%) compared with control group. In CRSST group, production of cytokines which shows suppressive effect on inflammation (IL-4, IL-10 ) are increased and which promotes inflammation (TNF-α, INF-γ) are decreased in blood. In CRSST group, production of immunogloblin (IgG2b, IgG3 and IgM) is reduced compared with control group, and rate of CD4+ and CD3+ T cell is lower in joint and higher in lymph node compared with control group. From above results it could be accepted that CRSST shows anti-arthritis effect via immune system especially through the controlling the inflammatory cytokines and immunoglobins. CRSST could be usefully applied for the prevention and treatment of RA. And also is expected to be clinically helpful on the treatment of RA through modification.

• IMMUNE NETWORK
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• 제11권5호
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• pp.258-267
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• 2011

Background: Current management strategies attempt to diagnose rheumatoid arthritis (RA) at an early stage. Transcription profiling is applied in the search for biomarkers for detecting early-stage disease. Even though gene profiling has been reported using several animal models of RA, most studies were performed after the development of active arthritis, and conducted only on the peripheral blood and joint. Therefore, we investigated gene expression during the initial phase of collagen-induced arthritis (CIA) before the arthritic features developed in the thymus in addition to the peripheral blood and synovium. Methods: For gene expression analysis using cDNA microarray technology, samples of thymus, blood, and synovium were collected from CIA, rats immunized only with type II collagen (Cll), rats immunized only with adjuvant, and unimmunized rats on days 4 and 9 after the first immunization. Arrays were scanned with an Illumina bead array. Results: Of the 21,910 genes in the array, 1,243 genes were differentially expressed at least 2-fold change in various organs of CIA compared to controls. Among the 1,243 genes, 8 encode T-cell receptors (TCRs), including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes, which were down-regulated in CIA. The synovium was the organ in which the genes were differentially expressed between CIA and control group, and no difference were found in the thymus and blood. Further, we determined that the differential expression was affected by adjuvant more than Cll. The differential expression of genes as revealed by real-time RT-PCR, was in agreement with the microarray data. Conclusion: This study provides evidence that the genes encoding TCRs including CD3${\zeta}$, CD3${\delta}$, CD3${\varepsilon}$, CD8${\alpha}$, and CD8${\beta}$ genes were down-regulated during the initial phase of CIA in the synovium of CIA. In addition, adjuvant played a greater role in the down-regulation of the CD3 complex compared to CII. Therefore, the down-regulation of TCR gene expression occurred dominantly by adjuvant could be involved in the pathogenesis of the early stage at CIA.