• Korean Journal of Plant Resources
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• v.21 no.4
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• pp.329-335
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• 2008

This study was intended to research into the possibility of corilagin (CRN) isolated from Euphorbia helioscopia as rheumatoid arthritis drug. For the study, CRN was medicated to the abdominal cavity of collagen induced arthritis (CIA) mice that was a animal model for rheumatoid arthritis and its effects on incidence and arthritis index (AI) were studied. The results were as folllows; Medicating corilagin that were isolated from Euphorbia heliscopia to CIA mice resulted in inhibiting an incidence of arthritis and reducing in arthritis index. It was found that inflammatory cells were remarkably decreased and joint cavity was well secured. Also it was displayed that the formation of pannus was not observed and a cartilage was preserved well by cell histological research. Performing fluorescence flow cytometry of CIA mice resulted in reducing in inflammatory cells infiltrated each tissue.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.3
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• pp.490-503
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• 2010

This study was carried out to know the effects of Gwanjul9-bang (hereinafter reffered to GJ9) on the inhibition of arthritis induced by collagen on DBA/1J mouse. For this purpose, GJ9 was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node and paw joint, rheumatoid factor (IgG, IgM) in serum were measured in vivo. The cytotoxicity against hFCs was not measured in any concentration. The hepatotoxicity was low in GJ9 treated group compared with MTX group. The arthritis index was decreased significantly. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was significantly decrease in paw joint. In lymph nodes, $CD19^+$, $CD3^+$, $CD4^+$, $CD3^+CD69^+$, $CD8^+$, $CD4^+CD25^+$, $CD3^+CD49b^+$, $CD4^+CD44^+$, $CD3^+CD8^+$ cells increased significantly, $B220^+CD23^+$cells decreased significantly. In joints, $CD3^+$, $CD4^+$, $CD4^+CD25^+$, $CD11b^+Gr-1^+$ cells decreased significantly. The levels of IgG and IgM was significantly decreased compared with control. Anti-collagen II in serum was significantly decreased compared with control. The degree of arthritis induced damage of joint of GJ9 group is slight compared with control group in histopathologic observation (Hematoxylin & Eosin, Masson's Trichrome). Comparison of the results for this study showed that GJ9 had immunomodulatory effects. So we expect that GJ9 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.2
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• pp.17-34
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• 2010

Objectives : This study was carried out to know the effects of Gwanjul8-bang(here in after reffered to GJ8) on the inhibition of arthritis induced by collagen on DBA/1J mice. Methods : For this purpose, GJ8 was orally administered to mouse with arthritis induced by collagen II. Cytotoxicity, hepatotoxicity, arthritis index, value of immunocyte in draining lymph node(DLN) and paw joint, cytokine in serum were measured in vivo. Results : 1. The arthritis index was decreased significantly. 2. In total cell counts of DLN and paw joint, the cells in DLN increased significantly while there was a significant decrease in paw joint. 3. In lymph nodes, $CD19^+$, $CD3^+$, $CD4^+/CD25^+$ cells increased significantly, and $B220^+/CD23^+$ cells decreased significantly. 4. In joints, $CD3^+$, $CD4^+$, $CD11b^+/Gr-1^+$ cells decreased significantly. 5. The levels of $TNF-{\alpha}$, IL-6, IL-17, MCP-1 and vascular endothelial growth factor(VEGF) in serum was significantly decreased compared with control. 6. Anti-collagen II in serum was significantly decreased compared with control. 7. The degree of arthritis induced damage of joint of GJ8 group is slight compared with control group in histopathologic observation(hematoxylin & eosin(H&E), Masson-Trichrome(MT) staining). Conclusions : Comparison of the results for this study showed that GJ8 had immunomodulatory effects. So we expect that GJ8 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore there seems to be many clinical research needed in the future.

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.117-137
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Gentianae macrophyllase Radix herbal-acupuncture solution(GR-HAS) at Joksamni(ST36) on Collagen-induced arthritis(CIA) in DBA/1J mice. The author performed several experimental items to analyze arthritis evaluation, change of weight, spleen size and adhesion rate, change of cytokine level, IgG, IgM and anti-collagen II , change of immunocyte count, histological change of CIA mouse joint related with RA. Results : 1. In the GR-HA group, the arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In GR-HA group, there were no weight loss and similarly maintained as normal group. Spleen size, adhesion rate and the edema and transformation of knee joint were low and similarly maintained as normal group. 3. In the GR-HA, cytokine level, IgG, IgM and anti-collagen II were significantly decreased. 4. In the GR-HA, the change of immunocyte count were similarly maintained as normal group. 5. In the histological changes of the CIA mouse joint, the cartilage destruction and synovial cell proliferation were decreased in the GR-HA(Hematoxylin and eosin stain). The collagen fiber expressions in the GR-HA were similar with that of the normal group(Masson's Trichrome stain) Conclusions : These results suggest that GR-HA at ST36 has an effect to control immune reaction and suppress inflammation, synovial cell proliferation and cartilage destruction in rheumatoid arthritis.

• The Korea Journal of Herbology
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• v.27 no.3
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• pp.1-6
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• 2012

Objectives : The present study was undertaken to evaluate whether Atractylodis Rhizoma Alba ethanol (ARA-E) extract, which is the pericarp of $Atractylodes$ $japonica$ Koidz. has an effect on collagen-induced arthritis (CIA) in mice. Methods : Male DBA/1J mice were induced by intradermal injection of bovine collagen-II in Freund's incomplete adjuvant (IFA). The CIA mice in the onset of arthritis were treated daily with oral administration of ARA-E extract at dose of 50 mg/kg/bw for 28 days. Arthritis index, histopathological changes and the levels of anti-type II collagen (CII) IgG and inflammatory cytokine, TNF-${\alpha}$ in sera of mice were measured to evaluate the antiarthritic effect of ARA-E. Results : ARA-E extract significantly decreased the arthritic scores and inhibited pathological changes of knee joint tissues in CIA mice. ARA-E extract also significantly decreased the serum levels of anti-CII IgG and TNF-${\alpha}$ in CIA mice. These results indicate that ARA-E extract may effectively prevent arthritic damages in CIA mice, at least partially, by inhibiting the production of autoantibodies and inflammatory cytokine. Conclusions : This studies suggest that ARA-E has a therapeutic potential in inflammatory joint diseases such as rheumatoid arthritis.

• The Korea Journal of Herbology
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• v.31 no.4
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• pp.1-10
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• 2016

Objectives: In Korean medicine, Curculiginis Rhizoma was treated for arthritis in remedy. But efficacy of Curculiginis Rhizoma on collagen induced arthritis was not revealed.Methods: Anti inflammatory effect of Curculiginis Rhizoma was researched in vitro with RAW264.7 cell and cell toxicity, levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) and PGE2 were analyzed by ELISA assay. Inflammatory protein were analyzed by western blotting assay (JNK, ERK, COX-2, TNF-α and IL-1β). In vivo, collagen induced arthritis mice model was used to evaluate anti-inflammation effect through arthritis index, immune cell number and cytokine levels (TNF-α, IL-6 and IL-1β) in serum.Results: ECR(Extract of Curculiginis Rhizoma) has not shown cell toxicity in 200 ㎍/㎖ on RAW264.7 cell. ECR suppressed releases of NO, TNF-α, IL-1β, IL-6, IL-12 and PGE2 on RAW264.7 cell treated with lipopolysacharide (1 ㎍/㎖). And ECR inhibited regulation of TNF-α, IL-1β and IL-6 mRNA, reduced protein release of JNK, ERK, iNOS, COX-2, IL-1β and TNF-α. AI of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly decreased compared to vihicle arthritis mice, the number of immune cell in foot joint was increased on control mice but those of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly reduced. This results correspond with contens of cytokines (TNF-α, IL-1β and IL-6) in serum.Conclusions: Curculiginis Rhizoma has anti-inflammation effect on RAW264.7 cell in vitro and collagen induced arthritis in vivo. So it is necessary to research more mechanism for cascade imfact.

• Journal of Acupuncture Research
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• v.17 no.1
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• pp.287-318
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• 2000

The purpose of this study is to observe the effect of Aqua-acupuncture utilizing Lycopi Herba Solution(LH-AS) on arthritis. For that purpose, we formed three experimental group, synovial cells of human body, normal BALB/C mice and DBA/1J mice with collagen II-induced arthritis, and measured the treatment effect of LH-AS on each group. The conclusions are as follows. 1. After the LH-AS treatment on synovial cells, there were no significant change in 1, 10, 50 and $100{\mu}g/m{\ell}$ whereas there was significant change in 200 and $400{\mu}g/m{\ell}$ in cytotoxicity. 2. IL-6, IL-$1{\beta}$, TNF-${\alpha}$ gene expression of synovial cells and the secretion amount of IL-6 and IL-$1{\beta}$ are significantly inhibited in treatment group with LH-AS. 3. The proliferation of synovial cells was significantly inhibited in treatment group with rIL-6, LH-AS 200 and rIL-6, $100{\mu}g/m{\ell}$. 4. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, the incidence of arthritis, hind paw edema, the index of arthritis and DTH were significantly inhibited. 5. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, splenetic weight was significantly increased and the number of leukocyte was significantly decreased. But there was no significant change in the number of platelet. 6. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, the number of $CD4^+$, $CD8^+$ activated cells and the surface-receptor expression were significantly increased whereas the number of $CD19^+$ activated cells and the surface-receptor expression were decreased. 7. After the DBA/1J mice with collagen II-induced arthritis were treated by LH-AS, total protein, LDH were significantly decreased, but there was no significant change in creatinine. 8. After the normal splenetic cells of BALB/C mice were treated by LH-AS and cultured, it was observed that the adherent cells were morphologically activated and IL-12 and IFN-${\gamma}$ gene expression were increased. 9. After the normal splenetic cells of BALB/C mice were treated by LH-AS and cultured, the number of $CD4^+$, $CD8^+$, $CD19^+$ activated cells and surface-receptor expression were inhibited when being compared with the control group. Taking all these observations into account, LH-AS injection is considered to be effective in treating arthritis and put to practical use in future arthritis clinic.

• Journal of Acupuncture Research
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• v.23 no.2
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• pp.125-137
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• 2006

Objectives : The effect of water extract of the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong), a traditional immuno-suppressive and immuno-activating Korean oriental medicine, on collagen-induced arthritis (CIA) mice model was studied. Identification of common Nokyong capable of affording protection or modulating the onset and severity of arthritis may have important human health implications. Methods : Nokyong has shown to possess anti-inflammatory and anticarcinogenic properties in experimental animals. In this study we determined the effect of DAE on collagen-induced arthritis in mice. Results : In three independent experiments mice given DAE in water exhibited significantly reduced incidence of arthritis (33% to 50%) as compared with mice given no DAE in water (84% to 100%). The arthritis index also was significantly lower in DAE-fed animals. Western blot analysis showed a marked reduction in the expression of inflammatory mediators such as cyclooxygenase 2 (Cox-2), $Interferon-{\gamma}\;(INF-{\gamma})$, and tumor necrosis factor ${\alpha}\;(TNF-{\alpha})$ in arthritic joints of DAE-fed mice. The neutral endopeptidase (NEP) activity was approximately 6-fold higher in arthritic joints of non-DAE-fed mice in comparison to nonarthritic joints of nonimmunized mice whereas it was only 2-fold higher in the arthritic joints of DAE-fed mice. Additionally, total IgG and type II collagen-specific IgG levels were lower in the arthritic joints of DAE-fed mice. Conclusion : Taken together our studies suggest that DAE may be useful in the prevention of onset and severity of arthritis.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.4
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• pp.33-49
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• 2010

Objectives : This study was designed to elucidate the anti-pathogenetic and curative effects of Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) on Type II collagen-induced arthritis(CIA) in mice. Methods : In experiment, twenty four mices were divided into non-treated normal group(n=6), bovine type II collagen-induced control group(n=6), collagen immunized and treated two group medicated with extract of GCP(concentration of extraction: 200 mg/kg n=6, 400 mg/kg n=6) for 4 weeks after collagen immunization, Various experimental such as arthritis, incidence, index, total cell number of spleen, total cell number of peripheral lymph node(PLN), paw joint total cell number, analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice, effects of inflammatory gene expression in spleen, PLN and paw joint of CIA mice, production of cytokine(IFN-${\gamma}$, IL-4, TNF-${\alpha}$, IL-6), analysis of rheumatoid factor(anti-collagen lgG, lgM level in serum) and histopathological study on the paw joint. The arthritis index, incidence were measured a week over 4 weeks after second boosting. Total cell number of spleen, peripheral lymph node, paw joint were measure after performed experiment over 7 weeks. Concentration of cytokine and rheumatoid factor in serum were measured after experiment finished. Histopathological study on the paw joint was measured after 40 days medicated with extract of GCP. Results : 1. Incidence of arthritis and index of arthritis were significantly decreased in treated group with 400 mg/kg. 2. Total cell number of spleen, PLN and paw joint were significantly decreased in treated group. 3. Analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice were significantly controled compare with control group. 4. Effects of inflammatory gene expression in spleen, PLN and paw joint of CIA induced mice were significantly controled compare with control group. 5. IFN-${\gamma}$, IL-6, TNF-${\alpha}$, concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. But IL-4 was significantly increased. 6. lgM and lgG concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. 7. Histopathologically, suppurative and destructive lesion of synovial membrane, articular cartilage and subchondral bony tissue in treated group were alleviated compare with those of control group. Conclusions : Based on the results described above, it might be consider that Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) has antiarthritic and analgesic effects and also inhibitory effects on the progression of collagen-induced arthritis mice.

• 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.