• Journal of Acupuncture Research
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• v.23 no.2
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• pp.73-90
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• 2006

Objectives : The effects of water extract of deer antler herbal-acupunture solution(DHS), prepared from the pilose antler of Cervus korea TEMMINCK var. mantchuricus Swinhoe (Nokyong), a traditional immunosuppressive and immune-activating Korean herbal- acupuncture, on collagen-induced arthritis(CIA:RA model) in mice was studied. Destruction of cartilage and bone are hallmarks of human rheumatoid arthritis, and controlling these erosive processes is the most challenging objective in the treatment of RA. Methods : We investigated the tissue protective effects of deer antler treatment using established murine collagen-induced arthritis(CIA) as a model. Potential synergy of low dosages of anti-inflammatory glucocorticosteroids and deer antler was also evaluated. Results : Treatment of established murine CIA with deer antler herbal-acupunture solution(DHS) $(10-50{\mu}g/day)$ suppressed disease activity and protected against cartilage and bone destruction. Although $10-50{\mu}g/day$ DHS had only a moderate effect on the inflammatory component of the disease activity, it strongly reduced cartilage pathology, as determined by histological examination. Serum cartilage oligomeric matrix protein(COMP) levels were significantly reduced, confirming decreased cartilage involvement. Histological analysis showed that bone destruction was prevented. DHS administration increased serum IL-1Ra levels and reduced anticollagen type II antibody levels. Treatment with low-dose $DHS(1{\mu}g/day)$ was ineffective in suppressing disease score, serum COMP or joint destruction. Synergistic suppression of both arthritis oseverity and COMP levels was noted when low-dose DHS was combined with prednisolone(0.05mg/kg/day), however, which in itself was not effective. Conclusion : DHS was shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption. These results indicated that the DAS is not only highly stable and applicable to clinical uses in bone resorption, but also it will be served as a potent anti-inflammatory and anti-arthritic agents for treatment of human RA.

• The Journal of the Korean dental association
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• v.54 no.4
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• pp.284-295
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• 2016

The aim of this study was to evaluate the effect of Epigallocatechin-3-Gallate (EGCG) on the alveolar bone metabolism in a collagen-induced arthritis (CIA) model in mice to enhance the understanding of rheumatoid arthritis (RA)-associated alveolar bone loss. Following the induction of CIA in animals (mice, n=16), mandibles were retrieved for micro-computed tomography (micro-CT) and isolation of alveolar bone cells (ABCs). In vitro osteogenic potentials of ABCs were evaluated and the mRNA expression of downstream effector genes was assessed. CIA was successfully induced in all animals, and micro-CT data showed that alveolar bone loss was significantly increased in the CIA group while the treatment of EGCG prevented the alveolar bone resorption. Osteogenesis by ABCs was significantly increased in the CIA+EGCG group in vitro. The analysis of mRNA expressions showed that osteoclastogenesis-associated genes were increased in CIA group while bone protecting genes were upregulated in EGCG treated group. The results demonstrate that EGCG downregulated the alveolar bone resorption in a CIA model in mice, and upregulation of bone protecting genes appear to be involved. Further studies are warranted.

• Herbal Formula Science
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• v.17 no.1
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• pp.99-111
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• 2009

Rheumatoid arthritis is characterized by focal loss of cartilage due to an up-regulation of inflammatory pathways, which produce pro-inflammatory mediators, such as interleukin-1(IL-1), tumour necrosis factor alpha($TNF-\alpha$), prostaglantin, and nitric oxide(NO). We investigated the anti-arthritic effects of water extracts from Pellodendri cortex and Atractylodis rhizoma in vitro and in vivo. Each extract suppressed the production of inflammatory mediators(NO, $IL-1\beta$, $TNF-\alpha$, and prostaglandin $E_2$) and the expression of inducible NO synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated macrophages in a dose-dependent manner. These suppressive effects were synergistically increased by their combination. The same results were also observed in the rat osteoblast sarcoma cell line ROS17/2.8 stimulated with $IL-1\beta$, $IFN-\gamma,$ and $TNF-\alpha$. Moreover, the combination of these water extracts significantly suppressed collagen-induced mouse arthritis. These results suggest that the combination of water-extractable components of Pellodendri cortex and Atractylodis rhizoma may be useful for therapeutic drugs against rheumatoid arthritis, probably by suppressing the production of inflammatory mediators.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.4
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• pp.810-817
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• 2002

This study was carried out to know the effects of sopunghwalhyeoltang-gamibang(hereinafter referred to SPHHT) on the inhibition of arthritis induced by collagen on the mouse. Various experimental were performed in vivo (in DBA/1 J mice which are experimental model of arthritis induced by collagen) to analyse the immunomodulatory effects of SPHHT. The results were obtained as follows: 1. The cytotoxicity against mLFC was not measured in all concentration. 2. The arthritis index, incidence, hind paw edema, delayed-type hypersensitivity reaction, spleen weight were reduced in SPHHT treated group. 3. The expression of CD3 ε +/CD4+, CD3 ε +/CD8+ and CD19+ in peripheral blood mononuclear were reduced in SPHHT treated group. 4. The production of pro-inflammatory cytokines such as IL-6 and TNF-α were significantly reduced in SPHHT treated group. 5. The formation of new bones and synivium were stimulated in SPHHT treated group. Comparison of the results for this study showed that Sopung-hwalhyeoltang-gamibang had immunomodulatory effects. So we expect that Sopunghwalhyeoltang-gamibang 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 Physiology & Pathology in Korean Medicine
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• v.22 no.6
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• pp.1416-1422
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• 2008

In order to examine anti-inflammatory effect of Anemarrhenae Rhizoma (AR) alcohol extract on rheumatoid arthritis, the present study investigated the viability and TNF-${\alpha}$ production in Raw264.7 cells treated with AR and collagen induced arthritis in DBA/1J mice which were orally administered with AR prior to immunization. The results are as follows: AR extract at 20 and 50${\mu}g$/ml inhibited the viability of Raw264.7 by 35% and 79%, respectively. AR showed a significant decrease in TNF-${\alpha}$ levels from Raw264.7 cells treated with LPS. AR administration significantly decreased arthritic index in DBA/1J mice immunized with bovine collagen type II. AR administration significantly decreased spleen weights obtained from mice in 6 weeks after immunization. AR administration significantly decreased serum anti-type II collagen antibody levels compared with control group. AR administration decreased serum IL-6 levels compared with control group but it did not reach statistical significance.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.83-83
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• 2001

Head of Panax ginseng indicates its growth number of years and it has been widely used for supplying energy to weak person. However, the underlying mechanisms are not sufficiently reported. Thus, we inclined to study head of Panax ginseng in rheumatoid arthritis and inflammation. Rheumatoid arthritis (RA), an organ-specific inflammatory disease of human, is characterized by a chronic and destructive inflammatory reaction and possibly autoimmune in etiology. It is occurred when the synobial membranes of joints and many other tissues of the body is attacked which induces significant health problem in terms of numbers of sufferers (U.S. incidence 23.7/100,000), and the synobial inflammatory is dominated by activated macrophage.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.403-411
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• 2003

For evaluating the effect of Siegesbeckiae Herba (here after abbreviated as SBH) on rheumatoid arthritis, the experiment was carried out; Incidence of rheumatoid arthritis, IRA(indices of rheumatoid arthritis), immunophenotypes by flow cytometer and histopathological changes in MRL/MpJ-Ipr-Ipr Mice in vivo were studied. The results were obtained as follows: 1. Incidence of RA in MRL/Ipr mice was suppressed to 60% of control by SBH. 2. IRA was significantly reduced for IgG3 and IgM at 20 weeks of age and for IgG2b at 12 and 20 weeks of age in mice by SBH compared with control. 3. Immunophenotypes such as CD4/sup +//CD25/sup +/, CD8/sup +//CD3e/sup +/, CD69/sup +//B220/sup +/, NK/sup +//CD3e/sup +/ were significantly increased by SBH compared with control. 4. In histopathological analysis, SBH suppressed the progression of PMN(polymorphonuciear leukocyte), leukocyte and fibroblast infiltration, and subsynovial soft tissue edema frequently showing in the early stage of the arthritis, and also effectively reduced the degeneration of cartilages and degenerative bone symptoms. These results suggest Siegesbeckiae Herba can be effectively applied to the treatment of rheumatoid arthritis and it is still necessary to isolate effective compound from Siegesbeckiae Herba in the near future.

• Korean Journal of Acupuncture
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• v.22 no.2
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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.

• IMMUNE NETWORK
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• v.11 no.5
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.871-877
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• 2008

Heme oxygenase-1 (HO-1), an inducible heme-degrading enzyme, is expressed by macrophages and endothelial cells in response to various stresses and mediators of inflammation. HO-1 has been recently implicated in regulation of angiogenesis via expression of VEGF. The purpose of this study was to determine the effects of HO-1 modulation on the collagen-induced arthritis (CIA) model and on angiogenesis via up- regulation of VEGF expression in human synovial fibroblast. DBA/1J mice were treated with an inhibitor of HO-1, tin protoporphyrin IX (SnPP), or with an inducer of HO-1, cobalt protoporphyrin IX (CoPP), from day 1 to day 35 after CIA induction. The clinical evolution of disease was monitored visually. At the end of the experiment, histopathologic changes were examined on the joints. VEGF expression in paws were measured by immunohistochemical stain. mRNA expression of HO-1 and VEGF stimulated with various concentration of $TNF-{\alpha}$, CoPP accessed on human synovial fibroblast by RT-PCR. Effects of pretreatment with SnPP on mRNA expression of HO-1 and VEGF in the presence of CoPP and $TNF-{\alpha}$ in synovial fibroblast was accessed by Real-time RT-PCR. Administration of cobalt protoporphyrin IX significantly induced the inflammatory response, with increased arthritis index and expression of VEGF in the paws of the arthritis models. Treatment with SnPP significantly reduced the severity of CIA through inhibition of joint inflammation and cartilage destruction. The expression of VEGF were also significantly reduced by SnPP treatment in the paw. CoPPIX as inducer of HO-1, increased HO-1 and VEGF expression dose dependently in synovial fibroblast. In contrast, inhibition of HO-1 activity by SnPPIX abrogated CoPPIX-induced HO-1 and VEGF production in synovial fibroblast. Stimulation with $TNF-{\alpha}$ increased HO-1 and VEGF expression itself and showed additive effect on HO-1 and VEGF expression when it treated with CoPP. When SnPP was treated with CoPP and $TNF-{\alpha}$, it abrogated the CoPP induced HO-1 and VEGF expression and also abrogated $TNF-{\alpha}$ induced HO-1 and VEGF expression in synovial fibroblast. The effects of HO-1 induction in rheumatoid arthritis results in aggravation of arthritis via up-regulation of VEGF. I concluded that inhibition of the expression or activity of HO-1 could be a therapeutic target of rheumatoid arthritis.