• Journal of Acupuncture Research
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• v.24 no.2
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• pp.211-220
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• 2007

Objectives : This study was to investigate the effect of high frequency electroacupuncture at $ST_{36}$ acupuncture point on the Complete Freund's Adjuvant (CFA) induced rat arthritis pain model. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups were divided into 4 groups; Normal, Control and Jok-Samri ($ST_{36}$) and Non-Acupuncture point (NA). Normal group, non-arthritic group, was injected with normal saline，and the others groups were injected CFA. $ST_{36}$ group was treated by 120 Hz electroacupuncture at $ST_{36}$ acupuncture point, and NA group was treated by 120 Hz electroacupuncture at non-acupuncture point. Each groups were evaluated by the change of c-fos positive neurons in periaqueductal gray (PAG) and hippocampus by using an image analyzer and a microscope. Results: - In the PAG region, the number of fos-positive cells in the $ST_{36}$ group ($42.37{\pm}5.08$) were significantly (p<0.05) decreased compared with the control group ($64.56{\pm}6.35$). - In the PAG region, the number of fos-positive cells in the NA group were meaninglessly decreased compared with the control group - In the Cornu Ammonis(CA)l region of hippocampus, the number of fos-positive cells in the $ST_{36}$ group ($7.00{\pm}1.08$) and NA group ($5.56{\pm}2.01$) were significantly (p<0.05) decreased compared with the control group ($13.81{\pm}1.24$). - In the dentate gyrus region of hippocampus, the number of fos- positive cells in the $ST_{36}$ group ($10.75{\pm}0.98$) and NA group ($6.56{\pm}0.78$) were significantly (p$26.45{\pm}1.82$). Conclusions : It is expected that high frequency electroacupuncture can be used a treatment of arthritic pain.

• Toxicological Research
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• v.29 no.3
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.92-104
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• 2002

Objective : Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory disease such as rheumatoid arthritis (RA). Autoimmunity to type II collagen (CII) may involve in the pathogenesis of RA. This study was performed to evaluate the effect of BV on type II collagen induced arthritis (CIA) with the naked eye, a immunohistochemical method and the examination of histology. Method : Male mice were immunized by subcutaneously injection of an $200{\mu}g$ emulsion mixed with bovine CII and complete Freund's adjuvant (CFA) twice for two weeks. In the control group, normal saline was injected, and in the experimental group, BV was applied. Result : The incidence of arthritis, the mean arthritis index and the number of the arthritic limbs of the BV group were all significantly lower than those of the control group. Among the pro-inflammatory cytokines, the production of $TNF-{\alpha}$ in the BV group was also suppressed compared with the control group, but $IL-1{\beta}$ was not. The examination on the histopathology of joints of CIA mice showed the effect of Bee Venom Herbal Acupuncture on the arthritis. Conculusion : Treatment with BV resulted in inhibition of development of arthritis and immune responses to CII.

• 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.

• Reproductive and Developmental Biology
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• v.35 no.2
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• pp.143-149
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• 2011

Arthritis is a common disease in aged people, and is clinically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Although common symptoms such as pain are present, the underlying pathological mechanisms are slightly different. Therefore, the objectives of the present study were to compare joint damage induced by RA and OA by analyzing the major morphological and molecular differences, and to propose a suitable therapeutic intervention based on the pathophysiological conditions of bones and joints. For the RA animal model, 8-week-old DBA1/J mice were immunized with bovine type II collagen emulsified in complete Freund's adjuvant (CFA). Normal C57BL/6 mice (over 2 years of age) were used for OA. The clinical arthritis score was calculated using a subjective scoring system, and paw thicknesses were measured using calipers. The serum TNF ${\alpha}$ level was analyzed using an ELISA kit. Micro-CT was used to identify pathological characteristics and morphological changes. In collagen-induced RA mice, there were increased ankle joint volumes and clinical scores (p<0.01). The concentration of TNF ${\alpha}$ was significantly increased from 3 to 7 weeks after immunization. Micro-CT images showed trabecular bone destruction, pannus formation, and subchondral region destruction in RA mice. OA among aged mice showed narrowed joint spaces and breakdown of articular cartilage. This study suggests that a careful therapeutic intervention between RA and OA is required, and it should be based on morphological alteration of bone and joint.

• Journal of Korean Medicine Rehabilitation
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• v.27 no.4
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• pp.33-53
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• 2017

Objectives This study was designed to review animal studies about the efficacy of herbal medicine for Rheumatoid arthritis animal model which was published in Korea after 2008. We also systematically investigated the reporting quality of the animal studies. Methods We systematically searched original articles in 8 databases since 2008. And manual searching was conducted through 10 Korean medicine journals from 2008. Studies were included if they used animal experimental model(s) with orally administered herbal medicine. Data were extracted regarding animal model, rheumatoid arthritis indicator and detail of intervention. Reporting quality of each study was also assessed by the STARA and ARRIVE guidelines. Results Nine hundred two articles were screened. Finally, 35 articles were included. 35 studies all showed that the herbal medicine used in the studies has significant effect on alleviating the macroscopic indicators, hematological indicators, histological indicators, genetic indicators, osteological indicator of Rheumatoid Arthritis and others. Species of animals was reported in 100% while ventilation and noise were reported in 0% in STRASA guidelines. Ethical statement was reported in 42.9%, experimental animals and sample size were reported in 24%, 29% and there was no study reporting funding. Conclusions These results suggest that herbal medicine might be effective treatment for Rheumatoid Arthritis. It should be improved by clinical studies. And there is a need for studying about efficacy and safety of each specific herbal medicine. And we should improve the Reporting quality of the animal studies published in Korea.

• 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.

• Physical Therapy Korea
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• v.13 no.3
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• pp.33-40
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• 2006

The purpose of this study was to assess the effects of High-Voltage Pulsed Current (HVPC) and ultrasound on adjuvant-induced arthritis in rats. Adjuvant arthritis was induced in female Sprauge-Dawley rats by the subcutaneous injection of a single dose of $.1m{\ell}$ of Complete Freund's Adjuvant (CFA) (1 mg of Mycobacterium Butyricum suspended in $.1m{\ell}$ paraffin oil) into the right hind paw. A randomized, parallel-groups design of 24 subjects was used. All rats were randomly assigned to control (n=8), ultrasound (n=8), and HVPC (n=8) were compared with those of injured rats. The rats in the pulsed ultrasound group were treated at 1 MHz frequency with $.5W/cm^2$ intensity in 1:4 mode for 5 minutes per day. The rats in the HVPC group were treated at 120 pulses per second and $50{\mu}s$ phase duration, 20 mA intensity for 30 min per day. Treatment was done in the left and right hind limb for 2 weeks. We evaluated clinical, radiographic, hematologic and histopathologic findings before and after treatment and obtained the following results. 1. Edema of the right hind paw was more significantly reduced in the ultrasound and HVPC groups than the control group on days 9, 12, and 14 (p<.05). Edema of the left hind paw was more significantly reduced in ultrasound and HVPC groups than the control group on days 12, 14 (p<.05). 2. WBC counts of the ultrasound and HVPC groups as compared with the control group were becoming remarkably decreased after the treatment. 3. In radiologic findings, arthritis formation was seen according to the score of arthritis, which was the highest in the control group, upon the observation of radiographs of the left and right hind paws. However, no statistically significant difference was present in the score within three groups. 4. In the histopathologic findings, ultrasound and HVPC groups had effectively suppressed erosions of articular cartilage and inflammatory cell infiltrations. Therefore, the results of the study show that rats that were treated with the ultrasound and HVPC effectively suppressed adjuvant arthritis. However, no statistically significant difference was present between the ultrasound group and the HVPC group.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.272-278
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• 2002

To investigate the anti-inflammatory and analgesic effects of Herba Chelidoniie, the extracts of Herba Chelidoniie treated in arthritic rat model. Complete Freund,s Adjuvant(CFA) were injected in the subcutaneous tissue of left foot paw of rats to induce arthritis. Herba Chelidonii extracts(HC) was administered immediately into the peritoneal cavity after CFA injection for 12 days. The immunohistochemical stainings for calcitonin gene-related peptide(CGRP) and substance P in the L4, L5 and L6 spinal dorsal horn and ganglia were done, and the paw swelling was measured with a micrometer and the blood leukocytes were counted. The results were as follows : The paw swelling of HC treated group was significantly decreased in 12th day after CFA injection compare to control group. The change of differential leukocytes counts of HC treated group increased the ratio of lymphocytes, and decreased the ratio of neutrophils compare to control group. The extent of CGRP immunoreactive nerve fiber of dorsal horn of HC treated group was weakly stained compare to control group. The number of CGRP immunoreactive neurons of L6 spinal cord of HC treated group was significantly decreased compare to control group. The extent of substance P immunoreactive nerve fiber of dorsal horn of He treated group was weakly stained compare to control group. The number of substance P immunoreactive neurons of L4, L5 and L6 spinal cord of HC treated group was significantly decreased compare to control group. These experimental results suggest that Herba Chelidonii extracts reduce the number of CGRP and substance P immunoreactive neurons and nerve fibers of spinal dorsal horns and ganglia, and decrease paw swelling in arthritic rat model, which may be closely related to analgesic and antiinflammatory effects of Herba Chelidonii.

• Journal of Acupuncture Research
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• v.29 no.1
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• pp.75-87
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• 2012

Objectives : The purpose of this study is to inquire into the effect of different concentrations of bee venom pharmacopuncture to inhibit genesis of pro-inflammatory cytokines and to inhibit nuclear factor (NF)-${\kappa}B$ activation on type II collagen induced arthritis. Methods : The experiment was divided into category of the normal group (NOR)-no treated group, control group (CON)-CIA (collagen induced arthritis) induced group, and 4,000 : 1 bee venom group (BV-L)- 4000:1 bee venom pharmacopuncture treated group after CIA, and 2000:1 bee venom group (BV-H)- 2,000 : 1 Bee venom pharmacopuncture treated group after CIA. RA was induced in the mice via injecting $50{\mu}{\ell}$ C II mixed CFA. The bee venom pharmacopuncture was applied on $ST_{35}$ for 19 days from the 3rd day of RA inducement. To research the effect on the expression of IKK ($I{\kappa}B$ kinase), iNOS (inducible nitric oxide synthase) & COX-2 (cyclooxygenase-2) mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. Results : The PMA-induced $I{\kappa}B$ kinase (IKK), inducible nitric oxide synthase (iNOS) and cyclooxygenase -2 (COX-2) mRNA expression were dose-dependantly decreased in bee venom treated with synoviocytes. In mice treated with bee venom pharmacopuncture, foot thickness and the damage of synovial membranes of the joint was lessened, and the activation of RA-related pro-inflammatory cytokines such as MIF, TNF-${\alpha}$ and MMP-9 was significantly decreased. The activation of iNOS and COX-2 was suppressed by the inhibition of NF-${\kappa}B$. In addition, each data was shown that 2,000 : 1 bee venom pharmacopuncture was more effective than 4,000 : 1 bee venom pharmacopuncture. Conclusions : It is speculated that bee venom pharmacopuncture has the therapeutic effect of palliating the damage of the synovial membrane and inflammation on RA by suppressing of NF-${\kappa}B$ activation.