• Journal of Acupuncture Research
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• v.22 no.2
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• pp.33-41
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• 2005

Objective : The effect of Ulmus davidiana Planch(UD), which has long been known to have anti-inflammation and protective effects on damaged tissue, inflammation and bone among other functions, on the development of type II collagen (CII)-induced arthritis (CIA) in rats was studied. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA)or saline during the experiment. When compared with rats treated with saline as control, UDHA at doses of more than $20{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-2, interleukin-6, $IFN-{\gamma}$ when the cells were obtained from rats 14 days after immunization and cultured in vitro with CII. Results : When rats were injected intraperitoneally, UD -treated group and control group rats did not differ significantly when low doses of UD was given to rats. Conclusion : The recommended dose of UD in the management and treatment of rat CIA will be more than $20{\mu}g/100\;g$, which is two-firth of human therapeutic dose. From the results, it was concluded that the effect of UDHA is dependent of dosage.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.195-200
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• 2015

We tested the hypothesis that micro-computed tomography (micro-CT) analysis provides a better quantitative readout of the therapeutic potential of methotrexate (MTX) for treating collagen-induced arthritis (CIA) in rats and compared to conventional histopathological examination. Rats were divided into three groups: Group 1 (G1) was treated with 0.9% saline, whereas groups 2 (G2) and 3 (G3) were boosted with type II collagen at days 0 and 7. Following the first collagen immunization, rats in G1 and G2 were treated with 0.9% saline and those in G3 were treated with 1.5 mg/kg MTX from day 14 to 28. All rats were sacrificed on day 28, at which point and all hind knee joints were analyzed by micro-CT and histopathological examination. Micro-CT analyses showed that bone volume and trabecular number were significantly decreased in G2 and G3 compared to G1 (p<0.01), as was percent bone volume (p<0.05 and p<0.01, respectively). However, bone surface/bone volume was significantly increased in G2 and G3 compared to G1 (p<0.05 and p<0.01, respectively). Trabecular separation was significantly increased in G3 compared to G1 (p<0.05). Histopathological examination showed that knee joints of rats in G2 and G3 showed severe joint destruction with inflammatory cell infiltration. However, cartilage destruction was slightly reduced in G3 compared to G2. Taken together, these results suggest that MTX treatment reduced cartilage destruction in rats with CIA, and micro-CT analyses made it possible to quantify arthritic bony lesion.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.97-114
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• 2011

Objectives : The object of this study is to observe the favorable anti arthritic effects of Sowhalrack-dan($Xi\check{a}ohu\acute{o}lu\grave{o}-d\bar{a}n$)(SWRD), which has been traditionally used in Korean medicine to treat rheumatoid arthritis on Freund's complete adjuvant(FCA) induced arthritic Wistar rats. Methods : Rheumatoid arthritis was induced by intradermal injection of FCA(10 mg in 1 ml paraffin oil 0.1 ml/rats). Each of 8 rats showing regular ankle circumferences per group were selected in 14 days after FCA treatment to confirm the induction of rheumatoid arthritis. 300, 150 or 75 mg/kg of SWRD was orally administered once a day for 14 days from 14 days after FCA treatments. Dexamethasone was intraperitoneally administered 15 mg/kg, once a day for 14 days from 14 days after FCA treatments. Rats were sacrificed after 14 days of continuous oral treatment of SWRD or intraperitoneal administration of dexamethasone, and changes were observed; the body weight, knee circumferences, gross arthritis score, inflammatory tissue $prostaglandin(PG)E_2$ levels and cartilage collagen, glucosaminoglycans compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatical decreases on the body weights, cartilage collagen contents and bone glucosaminoglycans - chondroitin sulphate, heparin sulphate and hyaluronic acid contents. Also, it increases the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels. However, these changes from FCA induced rheumatoid arthritis were clearly reduced due to the dexamethasone and both two different dosages of SWRD, 300 and 150 mg/kg in the present study. Although FCA induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg compared to SWRD 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats. Conclusions : The results obtained in this study suggest that over 150 mg/kg of SWRD showed favorable anti-arthritic effects on the FCA induced arthritis mediated by suppression of $PGE_2$. However, detailed mechanism studies are needed with the screening of the biological active compounds in SWRD. Although FCA induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg compared to SWRD 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats, in the present study.

• The Journal of Korean Physical Therapy
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• v.14 no.2
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• pp.65-73
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• 2002

OBJECTIVE: This study was Far infrared(FIR) irradiating to a rat collagen-induced autoimmune arthritis and observed nitric oxide level of spine. METHODS: Type II collagen(CII) in adjuvant was injected into rats on day 0. The results showed that rats injected with CII plus adjuvant had signs of autoimmune arthritis on day 14. Thereafter, Far infrared(FIR) irradiation was begun on day 15. The rats were irradiated FIR twice per day for 20 min each time. RESULTS: Seven days later(Day 22), the level of NO at FIR irradiated group(FRG; Arth+FIR) was decreased more than FIR-non irradiated group(FNRG; Arth). Twenty-one days later(Day 36), the level of NO at FRG was more closed to the control group's NO level than the FNRG. CONCLUSION: These results indicated that Far infrared irradiating appears to reduce the nitric oxide level at a rat model of autoimmune arthritis induced.

• The Journal of Korea CHUNA Manual Medicine
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• v.4 no.1
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• pp.75-88
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• 2003

Objectives : The purpose of this study is to find out the effects of Catalpa Ovata on the collagen-induced arthritis in the lewis rats. and we infere the effects of Catalpa Ovata on the rheumatoid arthritis in the human body. Methods : We investigated the effect of Catalpa Ovata on the Collagen-induced arthritis in Lewis rats via morphology, histology and serology as an experimental group, a control group, and a normal group. We feed Catalpa Ovata. only to an experimental group. Results : According to this research, the abnormal finding In Moire topography was 53.7% (1,018 students), and students needed X-ray re-examination were 11.2% (213 students). Students diagnosed scoliosis by X-ray re-examination were 1.8%. According to statistical analysis, interval between vertical base line of pelvis and vertical base line of neck, gap between left distance and right distance to the vertical base line of pelvis and difference of contour lines have strong correlations with deformity degree of the body surface examined by Moire. Conclusions : 1. The weight of an experimental group were lower than control group with statistically significant at 15 days later. 2, The paw edema volume of an experimental group were lower than control group at 10 days, 15 days later. but couldn't be found meaning. 3. The size of the tarsal joint of an experimental group were lower than control group at 5 days, 10 days, 15 days later, but couldn't be found meaning. 4. The volume of tumor necrosis factor-a at an experimental group were lower than control group with statistically significant. 5. The volume of interleukin-$1{\beta}$ at an experimental group were lower than control group with statistically significant. 6. An experimental group and a control group were showed ankylosing osteoarthritis, but an experimental group compared with a control group, alleviated In the fibrous ankylosis, destruction of articular cartilage and destruction of subchondral bony tissue. According to the above results, it might be considered that Catalpa Ovata has the suppression of the advance of the Collagen-induced arthritis and that result were presumed to bo connected with suppression of volume of the tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in the blood.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.83-88
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• 2015

CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) have been shown to play a regulatory or suppressive role in the immune response and are possibly relevant to the pathogenesis of autoimmune diseases. In the present study, we attempted to investigate the frequency of CD4+CD25+ Tregs in peripheral blood (PB) of collagen-induced arthritis (CIA) rats during the development of arthritis, to determine whether their frequency is involved in the immunoregulation of this disease. The results showed that normal rats had similar frequencies of CD4+CD25+ Tregs in PB during the experiment time, expressed as a percentage of CD4+CD25+Foxp3+ T cells among the CD4+ T lymphocyte population. In contrast, the frequency of CD4+CD25+Foxp3+ T cells in CIA rats was found to change during the development of arthritis. In CIA rats, there is a significant negative correlation between the frequency of CD4+CD25+Foxp3+ T cells and paw swelling (r=-0.786, p< 0.01). The relationship between the frequency of CD4+CD25+Foxp3+ T and immune activation was not found in normal rats. During the time course, the frequency of CD4+CD25+Foxp3+ T was lower in CIA rats than in normal ones. The data suggest that the frequency of PB CD4+CD25+ Tregs may be a promising marker for arthritis activity.

• Journal of Acupuncture Research
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• v.21 no.6
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• pp.51-62
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• 2004

Objective: To investigate the analgesic effect and its serotonergic mechanism, especially related with 5-HTI and 5-HT2 receptor, of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine type II (C II) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of spiroxatrine (5-HT1 receptor antagonist, 1mg/kg, intraperitoneal) and spiperone (5-HT2 receptor antagonist, 1 mg/kg, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited by pretreatment of spiroxatrine and spiperone in CIA. Conclusions : Jogsamni($ST_{36}$) EA showed analgesic effects in CIA The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by spiroxatrine and spiperone pretreatment. These observations suggest that 5-HT1 and 5-HT2 serotonergic receptor, which involve the release of serotonin neurotransmitter, play an important roles in analgesic mechanism of EA stimulation.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.2
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• pp.49-61
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• 2013

Objectives : This study was conducted to determine whether or not Kangwhaldoche-tang(Qianghuodaozhi-tang) (KDT) aqueous extracts can protect articular cartilage losses on the Freund's complete adjuvant(FCA)-induced rat rheumatoid arthritis. Methods : 520, 260 or 130 mg/kg of KDT were orally administered once a day for 14 days from 14 days after FCA treatments, and 15 mg/kg of dexamethasone was intraperitoneally administered as reference drug in this experiment. Changes on the body weight, knee circumferences, gross arthritis score, inflammatory tissue prostaglandin(PG) $E_2$ levels were monitored with cartilage collagen components and glucosaminoglycans(GAGs) compositions - chondroitin sulphate, heparin sulphate and hyaluronic acid in the present study. Results : As results of FCA treatment, classic rheumatoid arthritis featuring dramatic decreases of the body weights, cartilage collagen and GAGs contents with increases of the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels, were demonstrated in the present study. However, these changes from FCA - induced rheumatoid arthritis were clearly inhibited by treatment of dexamethasone and all three different dosages of KDT. Although overall anti-inflammatory effects of KDT 520 mg/kg were lowered than those of dexamethasone 15 mg/kg treated rats, KDT 520 mg/kg showed more favorable preserve effects on the cartilage GAGs and KDT 260 mg/kg treated rats showed similar preserve effects as compared with dexamethasone 15 mg/kg in this experiment. Conclusions : The present results supported that over 75 mg/kg of KDT showed favorable anti-arthritic effects on the FCA-induced arthritis mediated by suppression of $PGE_2$, representative inflammatory mediator, and may help improve rheumatoid arthritis.

• The Korea Journal of Herbology
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• v.26 no.3
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• pp.1-6
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• 2011

Objectives : The present study was undertaken to determine whether an ethanol extract of Citri Pericarpium (CP-E), which is the pericarp of Citrus unshiu Markovich is efficacious against collagen-induced arthritis (CIA) in mice. Methods : CIA was induced in male DBA/1J mice by intradermal injection of bovine collagen-II in Freund's incomplete adjuvant (IFA). The mice in the onset of arthritis were treated daily with oral administration of CP-E ethanol extract at different doses (50 and 100 mg/kg/bw) for 28 days. Arthritis index, histopathologic changes and the levels of TNF-${\alpha}$ as well as anti-CII IgG in blood were evaluated to confirm the anti-arthritic effect of CP-E on CIA in rats. Results : The results showed that comparing with untreated CIA mice, treated with CP-E extract significantly decreased the arthritic scores and the pathological changes of knee joint tissues, and also reduced the serum levels of TNF-${\alpha}$ and anti-CII IgG in CIA-mice. These results indicate that CP-E extract may effectively alleviate inflammatory response on CIA, and its anti-inflammation can be attributed, at least partially, to the inhibition of proinflamamtory cytokine, TNF-${\alpha}$ in CIA. Conclusions : This study suggest that CP-E has a therapeutic potential in inflammatory joint diseases such as rheumatoid arthritis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.1000-1007
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• 2011

This study was conducted to determine the analgesic effect of onion and acanthopanax senticosus mixture extract using the rheumatoid arthritis rat model. Rheumatoid arthritis model was made by the intradermal injection of type II collagen emulsified. Rats were divided into four groups: (1) Sham group(n=5), (2) Control group(administered DW 3 $m{\ell}$/1 day after RA induced, n=7), (3) Experimental group I(administered Onion extractor 600 mg/3 $m{\ell}$/1 day after RA induced, n=7). (4) Experimental group III(administered Onion and Acanthopanax senticosus mixture extractor 600 mg/3 $m{\ell}$/1 day after RA induced, n=7). After that, we examined the arthritic index, paw edema, pain threshold at 1st, 14th, 28th days. And also we examined histopathologic study(safranin-O green), immunohistochamical stain(COX-2) of knee joint at 28th days. Arthritic index, paw edema and pain threshold test were decrease in experimental group I, II than control group. Especially group II was most significantly inhibit effect than the other groups at 28th days. On the histopathologic view, all experimental groups were relieved and reproduced the erosion of arthritic site compared with control group. All experimental groups were COX-2 positive cells in the immunohistological stain of the knee joint were significantly decreased compared with control group. Especially group II was most significantly decreased than the other groups at 28th days. Onion and Acanthopanax senticosus mixture extractor can be used for curing rheumatoid arthritis. Anti-inflammatory effects may be somewhat better in combination of Onion and Acanthopanax senticosus.