• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.51-64
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• 2015

Objectives This study was carried out to investigate the effects of Gyejigabuja-tang extracts on the Monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of MIA into knee joint cavity of rats. Rats are divided into 4 groups (normal, control, positive comparison group, GBT group, each n=5). Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and oral medicated with distilled water. Positive comparison group was injected with MIA and taken Joins tablet 25 mg/kg. GBT group was injected with MIA and taken Gyejigabuja-tang extracts 300 mg/kg. Positive comparison group and GBT group were oral medicated for each substance once a day for 4 weeks. ALT, AST and creatinine were evaluated for hepatotoxicity and nephrotoxicity. Hind paw weight bearing ability was examined and inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), $PGE_2$, $LTB_4$, osteocalcin and deoxypyridinoline (DPD) within serum were analysed. Knee joint structures were observed by Hematoxylin & Eosin (H&E), Safranin-O staining method. Results 1. Function of liver and kidney was not affected. 2. Hind paw weight bearing ability was significantly improved. 3. IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ in experimental group were significantly decreased compared with control group. 4. $PGE_2$, $LTB_4$, Osteocalcin and DPD in experimental group were decreased compared with control group. 5. In histopathologic observation, injury on synovial membrane and cartilage of experimental group was lesser than control group (H&E, Safranin-O staining). Conclusions Based on these results, it can be suggested that Gyejigabuja-tang has anti-inflammation effects on the MIA-induced osteoarthritis in rats.

• The Korea Journal of Herbology
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• v.32 no.2
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• pp.41-47
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• 2017

Objective : The aim of this study is to investigate anti-arthritis activity using a korea's natural monument No. 265 designate 'Yeonsan-Ogye'. In this study, research by using extracts from different concentration of the Yeonsan-Ogye through an MIA-induced arthritis animal model was being conducted in vivo and scientifically verifying the efficacy of medicinal food. Methods : Yeonsan-Ogye was administered 500 mg/kg/day, 1000 mg/kg/day, 2000 mg/kg/day to SD-Rat, where arthritis was induced by monosodium iodoacetate (MIA) at $60mg/m{\ell}$. MMP-9, COMP, CTXII, calcitonin and glycosaminoglycan level in serum were measured by ELISA. The changes of relative hind paw weight bearing ratio by Incapacitance Test Meter and The cartilage of meniscus volume was examined and 3-D high-resolution reconstructions of the cartilage of meniscus were obtained using a Micro-CT system. Also, the histopathological analysis of knee was observed by H&E and safranin-O staining. Results : Production of MMP-9, COMP (all groups) and CTXII (500, 1000 mg/kg/day) level in serum was decreased, respectively, in comparison with control. The other way, production of calcitonin (500, 1000 mg/kg/day) and glycosaminoglycan (all groups) level in serum, Hind paw weight bearing ratio (all groups) was increased, espectively, in comparison with control. The cartilage of patella volume in micro-CT increased significantly. In addition, all groups showed a increase in the cartilage volume and proteoglycan. Conclusion : The results for Yeonsan-Ogye showed significant antiarthritis activity in serum and the cartilage. Therefore, it is thought to be that Yeonsan Ogye can be utilized as a variety of new korea medicie and health foods against arthritis diseases.

• Korean Journal of Acupuncture
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• v.22 no.2
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• pp.75-87
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• 2005

Objective : The purpose of this study is to observe the effect of Herbal-cupuncture with Acanthopanacis cortex Herbal-Acupuncture Solution (AC-HAS) on rheumatoid arthritis. Methods : The author performed several experimental items : it is paw thickness, weight of spleen, expression of $CD4^+,\;CD8^+,\;B220^+$ in the spleen, production of IL-6, $TNF-{\alpha}$, and examination of histology. Results : The obstain results are summarized s follows. 1. Treatment group were significantly inhibited the incidence of arthritis, hind paw edema and index of arthritis of CIA mice. 2. Treatment group were significantly decreased splenetic weight 3. The number of $CD4^+,\;CD8^+,\;B220^+$ activated cells were significantly inhibited in treatment group. 4. Treatment group were significantly decreased the amout of IL-4, $TNF-{\alpha}$ of CIA mice.. 5. Treatment group were expressed form of new bone, synoviumin and new margine in histology imperison to control group. Conclusions : Taking all these observations into account, AC-HAS injection is considered to be effective in treating rheumatoid arthritis and put to practical use in future rheumatoid arthritis clinic.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.4
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• pp.1001-1006
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• 2004

In order to examine the anti-arthritic properties of ShinEumHur(SEH)-herbal acupuncture, an adjuvant-induced arthritic rat was generated by the intra-articular injection of dried cells of Mycobacterium tuberculosis emulsified in squalene into the right knee joint. Fifty microliter of SEH extract was injected into Zusanli(ST36) acupoint on the ipsilateral hind paw every other day for 2 weeks. The body weight, knee circumference, squeak threshold, and weight distribution ratio were analyzed as the assessment methods addressing arthritic symptoms such as arthritic pain, edema, and tenderness. The weight distribution ratio was measured by a digital-type analgesia instrument using the dual channel scale that separately measures the weight the arthritic rat distributes to each hind paw, and thus quantifies both of swelling and pain severities at once. The therapeutic effects of SEH-herbal acupuncture, assessed by squeaking threshold and weight distribution ratio, were observed on 8th day after the arthritis induction as compared to saline group and control group. On 10th day, SEH-herbal acupuncture therapy significantly started to alleviate the growing pattern of knee circumference of an arthritic rat in the range of 0.2㎝. However, the loss of body weight was not significantly recovered. Taken together, the SEH-herbal acupuncture exhibited the significant therapeutic efficiency to treat adjuvant-induced monoarthritis in rat.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.3
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• pp.55-68
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• 2013

Objectives This study was to investigate the effects of Yuhyangjeongtong-san on the carrageenin-induced acute inflammation and adjuvant-induced arthritis in rats. Methods Acute inflammation was induced by injection of 2% carrageenin 0.15 ml into right hind foot of rats. Control group was carrageenin injected and taken distilled water, treated group was carrageenin injected and taken Yuhyangjeongtong-san by orally once. 2 hours after injection, plantar temperature and paw volume were measured. 3 hours after, counts of white blood cell (WBC) were performed. Arthritis was induced by injection of complete freund's adjuvant (CFA) into base of tail. Control group was CFA injected and taken distilled water, treated group was CFA injected and taken Yuhyangjeongtong-san by orally for 10 days. 0,5,10 day, body weight, thickness of ankle joint and paw edema were measured. 10 day, counts of WBC, $interleukin-1{\beta}$ ($IL-1{\beta}$) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) level were analysed. Histochemical study of NADPH-d and immunohistochemical study of c-fos were performed. Results In the carrageenin-induced acute inflammation, neutrophils of treated group were significantly decreased compared with control group. In the adjuvant-induced arthritis, paw edema, total counts of WBC and TNF-${\alpha}$ level in paw exudates were significantly decreased compared with control group, and the number of c-fos positive neurons of treated group was significantly decreased compared with control group. Conclusions On the basis of these results, we concluded that Yuhyangjeongtong-san have anti-arthritic and anti-inflammatory effects.

• The Korean Journal of Pain
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• v.34 no.2
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• pp.165-175
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• 2021

Background: Management of pain from open wounds is a growing unmet healthcare need. However, the models available to study pain from wounds or to develop analgesics for the patients suffering from them have primarily relied on incisional models. Here, we present the first characterized and validated model of open wound pain. Methods: Unilateral full-skin excisional punch biopsy wounds on rat hind paws were evaluated for evoked pain using withdrawal responses to mechanical and thermal stimulation, and spontaneous pain was measured using hind paw weight distribution and guarding behavior. Evaluations were done before wounding (baseline) and 2-96 hours post-wounding. The model was validated by testing the effects of buprenorphine and carprofen. Results: Pain responses to all tests increased within 2 hours post-wounding and were sustained for at least 4 days. Buprenorphine caused a reversal of all four pain responses at 1 and 4 hours post-treatment compared to 0.9% saline (P < 0.001). Carprofen decreased the pain response to thermal stimulation at 1 (P ≤ 0.049) and 4 hours (P < 0.011) post-treatment compared to 0.9% saline, but not to mechanical stimulation. Conclusions: This is the first well-characterized and validated model of pain from open wounds and will allow study of the pathophysiology of pain in open wounds and the development of wound-specific analgesics.

• Korean Journal of Pharmacognosy
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• v.25 no.3
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• pp.258-263
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• 1994

Ohjuksan has been used for the treatment of cold and pantalgia in traditional medicine. The anti-inflammatory activity of the aqueous extract from Ohjuksan (OJSE) was investigated utilizing acetic acid-induced edema and adjuvant arthritis in rats. The effects of this agent on acute toxicity and acetic acid-induced writhing syndrome in mice were also examined. OJSE did not showed acute toxicity at 2400mg/kg (p.o.) and 1200mg/kg(i.p.) body weight. It was also showed to have significant analgesic action on the writhing syndrome in mice induced by 0.7% acetic acid at 300,600mg/kg body weight. It showed anti-inflammatory activity in 5% acetic acid-induced edema and adjuvant arthritis with oral administration in rats and exhibited significant preventive effect on edema at 300 and 600mg/kg(p<0.01). In the method of adjuvant arthritis, orally administered for 19 days, it inhibited the hind paw edema in rats with 300 and 600 mg/kg body weight from 5 th day to 19th day. These results suggest that OJSE had analgesic and anti-inflammatory action.

• Physical Therapy Korea
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• v.10 no.2
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• pp.45-59
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• 2003

The purpose of this study was to assess the effects of ultrasound on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced in 26 female Sprauge-Dawley rats by the subcutaneous injection of a single dose of .1 mL of Complete Freund's Adjuvant (CFA) (1 mg of Mycobacterium Butyricum suspended in .1 $m{\ell}$ paraffin oil) into the right hind paw. After confirming inflammatory edema and arthritis in the paw 2 weeks later, the arthritic rats were divided into 3 groups, i.e., a control group, a pulsed ultrasound group (Group A), and a continuous ultrasound group (Group B) with 8 rats placed in each group. The rats in Group A were treated with pulsed ultrasound at 1 MHz frequency with .5 $W/cm^2$ intensity in 1 : 4 mode for 3 minutes. The rats in Group B were treated with continuous ultrasound at 1 MHz frequency with 2 $W/cm^2$ intensity in the continuous mode for 3 minutes. The ultrasound treatment was done in the left and right ankles for 2 weeks. Clinical, radiographic and histopathologic findings were then evaluated before and after treatment and yielded the following results. 1. No significant difference was present in body weight between the control group and the treated groups. 2. A statistically significant decrease in the edema of the paw was seen in the rats in Group A that was treated with pulsed ultrasound by 26~29 days after the treatment started (p<.05). 3. According to radiological examination, Group A showed the lowest score in arthritis scale which means it showed a tendency to suppress arthritic inflammation of the left and right hind paws. However, no statistically significant difference was present in the score between the control group, Group A and Group B. 4. According to histopathologic findings, the degree of infiltration by inflammatory cells and hypertrophy of the synovium were less in Group A compared with the control group and Group B. The results of the study show that rats that were treated with the pulsed ultrasound effectively suppressed adjuvant arthritis. However, more effort is needed to objectively prove the effectiveness of ultrasound by developing more sensitive testing methods that could quantitatively evaluate the treatment effects of acute rheumatoid arthritis and by trying out different ultrasound treatment methods.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.27-44
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• 2015

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund's adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases.

• 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.