• Journal of Acupuncture Research
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• v.26 no.6
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• pp.51-65
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• 2009

Objectives : This study was built to investigate the effect of Trachelospermi Caulis herbal-acupuncture on the Collagen-induced arthritis(CIA) in rats. Methods : Arthritis was induced by intradermal injection of Bovine type II collagen solution into base of tail. Experimental group were divided into 5 groups ; Normal(N) group, Control(C) group, Trachelospermi Caulis high(TH) group, Trachelospermi Caulis low(TL) group, Saline(S) group(n=7 for each group). Normal group was had no management. Control group was injected with Bovine type II collagen solution and taken no treatment. Trachelospermi Caulis high group was injected with Bovine type II collagen solution and taken high-intensity(10mg/kg) herbal-acupuncture treatment on $ST_{36}$. Trachelospermi Caulis low group was injected with Bovine type II collagen solution and taken low-intensity(5mg/kg) herbal-acupuncture treatment on $ST_{36}$. Saline group was injected with Bovine type II collagen solution and taken saline injection on $ST_{36}$. Body weight, paw edema volume and ankle joint thickness were measured during experimental day. On the last experimental day, we analyzed WBC count, TNF-$\alpha$ & IL-$1{\beta}$ concentration, c-fos immunohistochemistry and NADPH-d histochemistry for evaluating the effect of Trachelospermi Caulis herbal-acupuncture. Results : The results were as follows ; 1. In the change of paw edema volume, TH group only has significant difference compared with C group. 2. In the change of ankle joint thickness, TH group only has significant difference compared with C group. 3. In WBC count of serum, TH, TL groups have significant decrease compared with C group. 4. In TNF-$\alpha$ concentration of effusion, TH, TL groups have significant decrease compared with C group. and TH group has significant decrease compared with TL group. 5. In IL-$1{\beta}$ concentration of effusion, TH, TL groups have significant decrease compared with C group. and TH group has significant decrease compared with TL group. 6. In c-fos positive neurons of S1S2(cortex) region, TH, TL, S groups have significant decrease compared with C group. 7. In NADPH-d positive neurons of CPu(caudate putamen) region, TH, TL groups have significant decrease compared with C group. 8. In NADPH-d positive neurons of Tfp(transverse fibers of pons) region, TH, TL, S groups have significant decrease compared with C group. and TH group has significant decrease compared with S group. Conclusions : According to above results, we hope that Trachelospermi Caulis herbal-acupuncture may have the effect that decreases progression and development of CIA. And it can be suggested that Trachelospermi Caulis herbal-acupuncture may reduce the expression of c-fos and NOS.

• 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 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.

• Journal of Acupuncture Research
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• v.19 no.3
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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.

• 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.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.248-254
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• 2003

Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.

• Journal of Acupuncture Research
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• v.24 no.6
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• pp.15-27
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• 2007

Objectives : The purpose of this study is to investigate the effectiveness of Ulmus davidiana Planch herbal acupuncture(UA) to inhibit nuclear $factor(NF)-{\kappa}B$ activation on type II collagen-induced arthritis (CIA) in mice. Methods : Using an in vitro test, the synoviocytes picked out from the experimental CIA mice were subcultured. The synoviocyte cells were treated with phorbol-12-myristate-13-acetate(PMA) for 1 hour prior to the addition of indicated concentrations($0.4\;-\;1.0mg/m{\ell}$) of UA, and the cells were further incubated for 24 hours. The in vivo test, $NF-{\kappa}B$ p65, inducible nitric oxide synthase(iNOS), cyclooxygenase-2(COX-2), vascular cell adhesion molecule(VCAM)-1 production and apoptosis was observed by immunohistochemical staining. Results : The PMA-induced $I{\kappa}B$ kinase(IKK), iNOS and COX-2 mRNA expression were dose-dependently decreased in UA treated synoviocytes. Using the in vivo test, the number of eosinophils in mice treated with UA noticeably decreased in the the CIA group(P<0.05 using student t test). In mice treated with UA, there was less cartilage erosion. less bone destruction, mild synovial hyperplasia, mild fibrosis, and mild angiogenesis with less MIP-2 production. By immunohistochemical staining, suppression of $NF-{\kappa}B$ p65, iNOS production, inhibition of COX-2 production, inhibition of VCAM-1 production and inducing apoptosis were observed. Conclusions : These results suggest that UA might be applicable to the therapy of RA to suppress $NF-{\kappa}B$ activation.

• Journal of Acupuncture Research
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• v.19 no.5
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• pp.161-175
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• 2002

봉독은 거풍습(祛風濕), 지통(止痛), 해경평천(解痙平喘), 소종강압(消腫降壓)의 효능으로 오랫동안 통증과 염증성 질환을 치료하는데 이용되어져 왔는데 최근에는 면역관련질환치료에 응용하여 좋은 결과가 보고되고 있다. 본 연구는 Rheumatoid arthritis와 유사한 형태의 대표적 실험모델로 알려진 실험용 쥐의 Type II collagen 유발 관절염(Type II collagen induced arthritis : CIA)의 활액에서 봉독약침이 단백분해효소와 유리기 손상에 미치는 면역억제효과를 알아보기 위해 실행되었다. 본 실험에서는 CIA가 유발된 실험용 쥐에 봉독약침($5{\mu}l/kg$)을 처리한 실험군과 대조군으로서 CIA 유발 쥐에 생리식염수를 처리한 군(CIA군), 정상적인 쥐에 생리식염수로 처리한 군(정상군)으로 구분하여 각 군들의 일련의 표본에서 세포질, 리소좀, 간질성 단백분해효소의 활성과 유리기로 인한 단백질 손상정도를 (carbonyl 유도체를 측정하여)서로 비교하였다. 그 결과 각 군의 활액표본에서는 많은 종 류의 단백분해효소가 정산군보다 CIA군에서 유의하게 활성이 높았으며, 봉독약침($5{\mu}l/kg$)을 처리한 군에서 효소들의 활성이 유의하게 감소하였다. 그러나 각 군들의 혈장표본에서는 이 효소들의 활성은 서로 유의한 차이가 없었다. 이는 혈장속의 면역반응과 연관되리라고 추측되는 단백분해효소들의 활성변화는 병인적 측면에서 RA와 같은 염증성관절 질환과는 큰 상관성이 없다는 것을 의미한다. Carbonyl 유도체 측정으로 평가한 유리기 손상은 활액과 현장표본에서 모두 봉독약침($5{\mu}l/kg$)을 처리한 군에서 유의성 있게 감소하였다. 이상의 결과로 볼 때 단백분해효소와 유리기의 활성은 RA의 병인학적 측면에서 모두 잠재적인 중요성을 가지고 있으므로 향후 새로운 RA치료법은 이들 단백분해효소의 활성저해와 유리기의 소거능을 포함해야 한다고 사료되며 봉독약침은 이러한 2가지 효능을 포함한 효과적인 치료라고 평가된다.

• Journal of Acupuncture Research
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• v.18 no.4
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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.