• 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.

• Korean Journal of Acupuncture
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• v.24 no.3
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• pp.179-204
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Angelicae Radix Pharmacopuncture(AR-P) at Joksamni(ST36) on collagen II induced arthritis in DBA/1J mice. The authors evaluated arthritis index, arthritis incidence and joint edema, and measured body weight, spleen size and stenosis rate, serum cytokine level, serum antibody level, immune cell populations In spleen, lymph node, and knee joint, and performed histological analysis of CIA mouse joint. Results : In the AR-P group, arthritis index, arthritis incidence and joint edema were decreased, and the enlargement, malformation and stenosis of spleen and the malformation of joint appeared milder than the control group. In AR-P group, the levels of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $IFN-{\gamma}$ in serum were significantly decreased. And the level of anti-collagen II in serum was maintained lower in AR-P group than in the control group. In AR-P group, the level of $IFN-{\gamma}$ and IL-10, and $IFN-{\gamma}/IL-4$ ratio were significantly decreased, and the ratios of $CD3e^+$ cells to $CD45^+$ cells, $CD4^+$ cells to $CD8^+$ cells in spleen were similarly maintained as those of the normal group. In the AR-P group, the populations of $CD4^+/CD25^+$ cells in spleen and lymph nodes, $CD45R^+/CD69^+$ cells in lymph nodes, $CD3^+/CD69^+$ cells and $CD11b^+/Gr-1^+$ cells in knee joint were decreased. In the histological analysis, the cartilage destruction, synovial cell proliferation and the collagen fiber destruction were decreased in the AR-P group Conclusions : The results suggest that AR-P at right ST36 has a therapeutic effect on collagen-induced arthritis in mice.

• Natural Product Sciences
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• v.13 no.4
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• pp.283-288
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• 2007

Acanthopanacis Cortex (AC) has been popularly used as an herbal medicine for medical treatment of rheumatoid arthritis, insomnia, impotence and diabetes. Here, we investigated immunostimulating effects of the aqueous extract of AC on macrophage. We studied nitric oxide (NO) and tumor necrosis factor (TNF)-${\alpha}$ release in response to AC treatment, as they are important secretory products of macrophage. AC alone induce the NO and TNF-${\alpha}$ production. AC increase c-Jun NH2-terminal kinase 1/2 (JNK) and extracellular signal-regulated kinase (ERK) phosphorylation but does not p38 activation in RAW 264.7 cells. Also AC resulted in the enhanced cell-surface expression of CD80 and CD14. In addition, AC resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon (IFN)-gamma. After feeding with AC to mouse for 10 days, the change of $CD28^+$ and $CD40^+$ population was analyzed. AC increased $CD28^+$ population in splenocytes in vivo. These studies indicate that AC induces macrophage activation and suggest the possible use of AC in macrophage-based immunotherapies.

• Journal of Acupuncture Research
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• v.24 no.6
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• pp.45-61
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• 2007

Objectives : The purpose of this study is to observe the effects of Carthami Flos herbal-acupuncture (CF-HA) at Joksamni($ST_{36}$) on arthritis in mice induced by Collagen II. Methods : The author performed several experimental items, including arthritis evaluation, change in weight, spleen size and stenosis rate, change in cytokine level, IgG, IgM and anti-collagen II, change of immunocyte count and histological change of the CIA mouse joint. Conclusions are as follows: Results : 1. In the CF-HA, the arthritis index and rate and the incidence of arthritis were decreased as the experiment proceeded. 2. In the CF-HA, spleen swell and stenosis, joint edema and change were decreased. 3. In the CF-HA, the level of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ and $IFN-{\gamma}$ in blood serum were significantly decreased. 4. In the CF-HA, the level of IgG, IgM and anti-collagen II were decreased. 5. In the CF- HA, $IFN-{\gamma}$, $IFN-{\gamma}/IL-4$, IL-10 of the culture fluid was decreased. 6. In the CF-HA, the cell rate of $CD3e^+$ and $CD45R^+$, $CD4^+$ and $CD8^+$, $CD4^+/CD25^+$ in spleen was similar to the cell rate of the normal group. 7. In the CF-HA, the cell rate of $CD4^+/CD25^+$, $CD45R^+/CD69^+$ in a lymph node was decreased as in the normal group. 8. In the CF-HA, the cell rate of $CD3^+/CD69^+$, $CD11b^+/Gr-1^+$ in joints was decreased as in the normal group. 9. In the CF-HA, the cartilage destruction and the inflammation cell growth in the H&E stain were decreased. The collagen fiber in the M&T stain were less destructed, therefore the result was similar to the normal group. Conclusions : These results suggest that CH-HA at $ST_{36}$ has an effect in controlling immune reaction and suppressing inflammation in rheumatoid arthritis therefore, the continuous flow of the following study is expected.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1323-1329
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• 2005

This study was carried out to know the immunity responses of Sogyughwalhyel-tanggami(SGHHT) to on Rheumatoid Arthritis in Collagen-induced Arthritis(CIA) Mice. Various experimental were peformed to analyse the immunity effects of SGHHT. The cytotoxicity against mLFCs was not measured. The production of pro-inflammatory cytokines $IL-1{\beta}$, IL-6, $TNF-\alpha$ were reduced in hFLSs. The production of pro-inflammatory cytokines $IFN-\gamma$, IgG3, IgG2b, IgM were reduced. Comparison of the results for this study showed that SGHHT had immunomodulatory effects of suppressing or enhancing. So we expect that SGHHT 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.

• Food Science and Biotechnology
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• v.16 no.4
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• pp.594-599
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• 2007

In this study, we evaluated whether the oral administration of chondroitin from the cartilage of Raja kenojei is effective on the progression of rheumatoid arthritis (RA), using collagen-induced arthritic (CIA) mice. Arthritis development was delayed dose-dependently in the chondroitin-treated groups. The pre- and late-treated groups receiving 1,000 mg/kg of chondroitin had clinical scores that were reduced significantly by 56.9 (p<0.05) and 43.3% (p<0.05), respectively, compared to the vehicle-treated groups. Hematoxylin eosin staining and X-ray radiography showed that the chondroitins reduced the infiltration of inflammatory cells and prevented joint destruction of the knee and paw. Reverse transcription-polyerase chain reaction analysis revealed that chondroitin administration inhibited the expressions of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), $interlukin-1{\beta}$ ($IL-1{\beta}$), and $interferon-{\gamma}$ ($IFN-{\gamma}$) in joints more than the administration of vehicle. Chondroitin treatment also decreased the production of rheumatoid factors (RF), IgG and IgM, in the serum of CIA mice. These results indicate that chrondroitin administration has a protective effect involving the inhibition of pro-inflammatory cytokine production in CIA mice.

• Herbal Formula Science
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• v.21 no.1
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• pp.161-176
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• 2013

Objectives : To clarify the anti-arthritic activity of Ostericum koreanum Maxim. (OS) plus Aralia continentalis Kitagawa (AC) in vivo. Methods : All mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with OS plus AC once a day for 7 weeks. Oral administration of OS plus AC (200 or 50 mg/kg) significantly suppressed the progression of CIA, which extend is comparable to that of methotrexate (MTX, 0.3 mg/kg), a positive control. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Results : Administration of OS plus AC significantly suppressed the progression of CIA and inhibited the production of TNF-${\alpha}$ and IL-6 in serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with OS plus AC. In conclusion, our results demonstrates that OS plus AC significantly suppressed the progression of CIA and that this action was characterized by the decreased production of IL-6, IFN-${\gamma}$ and collagen II specific antibody in serum, CD3+CD69+ T cells, MHC class II+/CD11c+ (in DLN), CD11b+Gr-1+ cells (in PBMC), CD11b +Gr-1+ cells, B220+/CD23+ (in paw joint). Conclusions : The the levels of IFN-${\gamma}$ in the culture supernatant of splenocytes stimulated with CD3/CD28 or collagen were dramatically decreased, while those of IL-4 was increased. In the serum of OS and AC-treated mice, the levels of IgM RA factor were decreased.

• Journal of Acupuncture Research
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• v.19 no.6
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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.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.191-206
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• 2006

Objective & Methods : The purpose of this study is to observe the effects of Angelicae Pubescentis Radix herbal-acupuncture solution(APR-HAS) at Joksamni(ST36) on collagen IT induced arthritis in DBA/1J mice. The author performed several experimental items to analyze several cytokines and immune cells related with RA. Results : 1. In the APR-HA group, the incidence of arthritis and arthritis index were significantly decreased. 2. In APR-HA group, the levels of IL-6, $INF-{\gamma}$, $TNF-{\alpha}$, IgG, IgM, $IL-{\beta}$ and Anti-collagen II in serum of the CIA mouse were significantly decreased. 3. In APR-HA group, the level of $IFN-{\gamma}$, IL-4 in the CIA mouse spleen cell culture were significantly decreased. 4. In histology, the cartilage destruction and synovial cell proliferation were decreased in the APR-HA group, and the collagen fiber expressions in the APR-HA group were similar with that of the Normal group. 5. In the APR-HA group, CD3e+/CD19+ and CD4+/CD8+ were similarly maintained as Normal group in the CIA mouse lymph nodes, 6. In the APR-HA group, CD3e+/CD69+ was significantly decreased in the CIA mouse joint. 7. In the APR-HA group, CD11a+/CD19+ and CD11b+/Gr-l+ were significantly decreased in the CIA mouse lymph nodes 8. In the APR-HA group, CD4+/CD25+ was decreased in the CIA mouse spleen cell. 9. In the APR-HA group, CD4+/CD25+ was similarly maintained as Normal group in the CIA mouse lymph nodes.

• Journal of Acupuncture Research
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• v.24 no.5
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• pp.171-183
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• 2007

Objectives : The purpose of this study was to analyze the effects of Erythrinae Cortex herbal-acupuncture solution(EC-HAS) at the Joksamni($ST_{36}$) of mice with collagen II-induced arthritis(CIA). Methods : The author performed several experimental procedures to observe the effects of the EC-HAS at the arthritis. The severity of arthritis, changes of cytokine level and antibody level, histological changes of the CIA mouse joint were analyzed. Results : 1. The incidence of arthritis and arthritis index were significantly decreased in the cases which were treated with the EC-HA. 2. Cartilage destruction and synovial cell proliferation were reduced, and the expression of the collagen fibers was similar with that of the normal group. 3. The levels of IL-6, $IFN-{\gamma}$, $TNF-{\alpha}$, $IL-1{\beta}$ in serum of the CIA mice which were treated with the EC-HA were significantly decreased compared with those of the normal group. 4. The levels of IgG, IgM and anti-collagen II in serum of CIA mice when they treated with the EC-HA were significantly decreased compared with those of the normal group. 5. The expression ratio of $CD4^+$ to $CD8^+$ cells in the EC-HA treated mice were maintained as much as the normal group of the lymph nodes in the CIA mice. 6. The $CD3e^+CD69^+$ and $CD11b^+Gr-1^+$ cell populations in the knee joint were significantly decreased in the EC-HA treated group. Conclusions : These results suggest that the EC-HA at the ST36 may be responsible roles to control on the synovial cell proliferation and to prevent the cartilage destruction in rheumatoid arthritis. These results will be important supporting evidence for the practical use of the EC-HA at rheumatoid arthritis clinic in the future.