• 대한한의학회지
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• 제31권2호
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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.

• 약학회지
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• 제52권5호
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• pp.394-401
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• 2008

In order to access the suppressive effects of piroxicam (PX) and hydrolyzed products of Scutellariae Radix (PSH) on arthritis, we investigated whether PSH gel could suppress the progression of collagen-induced arthritis. PX, one of nonsteroidal anti-inflammatory drugs has been used in the systemic and topical treatment in a variety of inflammatory conditions. Scutellariae Radix, one of the herbal medicines, was used for the purpose of anti-inflammatory and anti-bacterials. For the purpose of transdermal absorption of the hydrogel preparations, two classes of hydrogels (PX, PSH) were formulated with carbomer 940, diethylene glycol monoethyl ether, polyethylene glycol-8-glyceryl caprylate/caprate and triethanolamine. In carrageenan-induced edema in rat hind paws, inhibition of foot swelling was more increased in PSH than PX hydrogel. Rheumatoid factors including serum IgG, IgM and collagen specific antibody were present much lower in PSH gel treated mice than control. Histological examination revealed that PSH hydrogel inhibited infiltration of inflammatory cells into affected paw joint, compared with control. The PSH hydrogel would be a suitable preparation to increase transdermal treatment for anti-inflammatory effects on collagen-induced arthritis.

• 한방재활의학과학회지
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• 제19권1호
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• pp.57-71
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• 2009

Objectives : The aim of this study was to know the immunity reponse of Esubwhaltong-tang(hereafter referred to ESWTT) to rheumatoid arthrits in CIA(collagen induced arthritis) mice. Methods : For this purpose, ESWTT was orally administerd to mice with arthritis induced by collagen II and then value of immunocyte in paw joint, cytokine(IL-6, $TNF-{\alpha}$), rheumatoid factor(IgG and IgM) and collagen II specific antibody in the serum were measured. Results : 1. The cytotoxicity was not shown on hFLSs and liver. 2. Marginal erosion, necrotic chodrocytes, cartilage and bone degradation were improved in histological section of paw joints from CIA mice(ESWTT extract administration group). 3. Total cell number of paw joint in CIA mice(ESWTT extract administration group) was decreased significantly. 4. The absolute number of CD3+, CD3+/CD69+, CD4+, CD4+/CD25+, CD49b+, CD3+/CD49b+ cells in CIA mice(ESWTT extract administration group) were decreased significantly. 5. The levels of IL-6 and $TNF-{\alpha}$ in the serum of CIA mice(ESWTT extract administration group) were decreased significantly. 6. The levels of total IgG and IgM in the serum of CIA mice(ESWTT extract administration group) were decreased significantly. 7. The level of collagen II specific antibody in the serum of CIA mice(ESWTT extract administration group) was decreased significantly. Conclusions : Comparison of the results for this study showed that ESWTT had immunomodulatory effects of suppressing. So we expect that ESWTT could be used as an effective drugs for not only rheumatoid arthritis but also auto-immune disease.

• 동의생리병리학회지
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• 제27권4호
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• pp.416-421
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• 2013

Cirsium japonicum var. ussuriense is often used in treatment of human disease such as hemorrhage, blood congestion and inflammation. The present study has been undertaken to investigate the effect of the leaf extract from C. japonicum var. ussuriense (CLE) on the development of collagen-induced arthritis (CIA) in DBA1/J mice. CLE administration suppressed markedly the arthritis incidence and arthritis score in CIA mice. Also, CLE significantly suppressed the release of $PGE_2$, TNF-${\alpha}$, IL-4 and IL-6 in CIA mice. However, CLE significantly increased the production of IL-10, but not IL-4. These results suggest that CLE suppress inflammatory mediators and regulates Th1 and Th2 cytokines. These properties may contribute to the anti-arthritis action of CLE.

• Korean Journal of Acupuncture
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• 제24권2호
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• pp.163-184
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• 2007

Objectives & Methods : The purpose of this study is to observe the effects of Phellodendri Cortex Herbal-acupuncture solution (PC-HAS) at Joksamni (ST36) on collagen II induced arthritis 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, chang of immunocyte count, histological change of CIA mouse joint. Results : 1. In the PC-HA group, arthritis index, the incidence of arthritis and joint edema were significantly decreased. 2. In the PC-HA group, the change of spleen size, spleen adhesion rate and the knee joint were significantly decreased. 3. The levels of $IL-1{\beta}$, IL-6 and INF- in serum of the CIA mouse were significantly decreased by PC-HA. 4. The levels of IgG, IgM and anti-collagen II in serum of the CIA mouse were significantly decreased by PC-HA. 5. In the CIA mouse spleen cell culture, the levels of IFN- , IFN- / IL-4, IL-10 were significantly decreased by PC-HA, but the level of IL-4 was significantly increased by PC-HA. 6. In the PC-HA group, the ratios of $CD3e^+$ to $CD45R^+$ cell, $CD4^+$ to $CD8^+$ cell and $CD4^+/CD25^+$ cell were similarly maintained as normal group in the CIA mouse spleen cell. 7. In the PC-HA group, $CD4^+CD25^+$ and $CD45R^+/CD69^+$ cell were significantly decreased in the lymph nodes. 8. In the PC-HA group, $CD3^+/CD69^+$ and $CD11b^+/Gr-1^+$ cell were significantly decreased in knee joint. 9. In histology, the cartilage destruction and synovial cell proliferation in the PC-HA group were similar with that of the normal group and the collagen fiber expressions in the PC-HA group were similar with that of the normal group. Conclusions : Form the result above, the results suggest that the PC-HA at ST36 has significant effect on collagen-induced arthritis, and can be put to practical use in the future rheumatoid arthritis clinic.

• Journal of Acupuncture Research
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• 제19권3호
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• pp.14-25
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• 2002

Objective : The purpose of this study was to investigate the effects of Aurothiomalate acupuncture containing Sodium Aurothiomalate on Type II collagen-induced arthritic DBA/1 mice. Methods : The mice were divided into three groups, one control group and two test groups. The control group was injected with saline on Choksamni(ST36) and the two test groups were injected either with Aurothiomalate acupuncture into Choksamni(AT1 group), or with Aurothiomalate acupuncture into Hwando(G30, AT2 group). We measured the incidence of arthritis, the mean index of arthritis, the number of arthritic limbs for the clinical examination and evaluation. We also examined the changes in the level of TNF-$\alpha$ and IL-$1{\beta}$. Results : 1. The incidence of arthritis in mice of the AT1 and AT2 groups were significantly lower than that of the control group. 2. The mean indices of arthritis in mice of the AT1 and AT2 groups were significantly lower than that of the control group. 3. The mean number of arthritic limbs in mice of the AT1 and AT2 groups were significantly lower than that of the control group. 4. The levels of TNF-$\alpha$ of the mice in the AT1 and AT2 groups were significantly different from that of the control group. 5. The levels of IL-$1{\beta}$ of the mice in the AT1 and AT2 groups were not significantly different from that of the control group. Conclusion : These results indicate that the treatment with Aurothiomalate acupuncture could improve the clinical status of Arthritis by suppressing immune responses in the mice of Type II collagen-induced arthritic.

• 한방재활의학과학회지
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• 제19권2호
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• pp.89-102
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• 2009

Objectives : This study was carried out to understand the immunity responses and anti-oxidation effect of the Gamidaeganghwal-tang(GDT) on rheumatoid arthritis by using the THP-1 cells and the serum of CIA mice. Methods : For this purpose, GDT was orally administerd to mice with rheumatoid arthritis induced by collagen II. To investigate the immunity responses, value of cytokine and gene expression in the THP-1 cell, levels of cytokines in the serum of CIA(collagen type II induced arthritis) mice, number of immunocyte in PBMC of CIA mice were measured. Then, anti-oxidant activity, scavenging activity on DHHP(2,2-diphenyl-1-picrylhydrazyl) free radical and SOD(Superoxide dismutae)-like activity of GDT was observed. Results : 1. The levels of IL-$1{\beta}$, IL-6, IL-8, MCP-1 at 100, $50{\mu}g/m{\ell}$ of GDT were significantly reduced in the THP-1 cell. 2. The levels of TNF-${\alpha}$, COX-2 mRNA expression at 100, $50{\mu}g/m{\ell}$ of GDT and IL-$1{\beta}$, IL-6 at $100{\mu}g/m{\ell}$ of GDT were significantly reduced in the THP-1 cell line. 3. The levels of IL-6, TNF-${\alpha}$ and IL-$1{\beta}$ were significantly reduced in the serum of CIA mice. 4. The absolute number of CD3+, CD4+ and CD8+ cells were significantly induced, CD3+/CD69+, CD3+/CD49+, CD19+, B220+/CD23+ cells were significantly reduced in PBMC. 5. Scavenging activity on DPPH free radical and SOD-like activity were significantly induced in a concentration dependent manner. Conclusions : Taking all these observations, GDT considered to be effective in treating rheumatoid arthritis. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

• 대한약침학회지
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• 제10권2호통권23호
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• pp.31-40
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• 2007

Objective : The aim is to examine the effect of Soyeum Pharmacopuncture (SPP) on collagen-induced arthritis (CIA) in DBA/1OlaHsd mice. Methods : To determine the effect of SPP on chronic IFNlammatory joint disease, we induced CIA in DBA/1OlaHsd mice by immunization with bovine type II collagen. Animals were treated with intraperitoneal injection doses of 2 mg/kg of SPP, beginning 3 days before the expected onset of disease symptoms. Inhibitory Effects of SPP were observed by serum levels of TNF-${\alpha}$, and IFN-${\gamma}$,,, or cell proliferation in the spleen cell culture and histological examination of knee joint. Results : In the CIA Mice, serum levels of TNF-${\alpha}$, and IFN-${\gamma}$,, production in the spleen cell culture were reduced. At the histopathological examination of knee joint, chondropathy of cartilage in the synovial joint in the SP group was repaired while compared with control group. Conclusion : These results suggest that the SPP may be effective for the prevention and treatment of rheumatoid arthritis disease.

• Journal of Ginseng Research
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• 제33권2호
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• pp.149-154
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• 2009

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and progressive cartilage and bone erosion. Korean red ginseng (KRG) has been shown to have an anti-inflammatory effect by inhibiting the secretion of inflammatory cytokines like $TNF-{\alpha}$, IL-1, -6, and -8, and $IPN-{\gamma}$. In this study, whether KRG extract has an inhibitory effect on the collagen-inducible development of arthritis in DBA/1J mice was investigated. To induce arthritis, type II collagen emulsified in Complete Freund's Adjuvant was intradermally injected into the base of the tails of mice. Three weeks after the initial injection, a booster injection of type II collagen emulsified in Incomplete Freund's Adjuvant was administered. The oral administration of KRG extract for 8${\sim}$10 weeks at the dose of 300 mg/kg (three days a week) inhibited the development of arthritis in the experimental group, compared to the control group which was given saline. While the administration of KRG extract three times a week demonstrated both preventive and inhibitory effects, the administration of KRG extract once a week had little inhibitory effect. In other studies, the regimen of KRG administration has been shown to decrease the plasma level of inflammatory cytokines like IL-8 and TNF-${\alpha}$, but the plasma levels of these cytokines were not decreased in the present study. The results of the present study suggest that KRG has preventive and inhibitory effects on collagen-induced arthritis.

• Journal of Acupuncture Research
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• 제28권1호
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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.