• The Korea Journal of Herbology
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• v.27 no.1
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• pp.1-10
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• 2012

Objective : To investigate effects of herbal preparations formulated(Gihyeolgwanjeolbang-A, CWS-A) on complete Freund's adjuvant (CFA)-induced arthritis in rats. Method : Arthritis was induced by injecting CFA subcutaneously into the left knee joint and paw, and the herbal preparations formulated(CWS-A I, 82.3 mg/kg ; CWS-A II, 164.6 mg/kg) was administered orally (i.g.) for 10 consecutive days beginning on day 10 after the injection. External shape, paw edema, inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), and histological observation were assessed. Result : In swelling of the paw, CWS-A I and CWS-A II group in 15 days and 20 days were significantly reduced compared to controls. In serum ALT, CWS-A I and CWS-A II group were significantly reduced compared to controls. In TNF-${\alpha}$, CWS-A I and CWS-A II group were a tendency reduced compared to controls. In HGB, HCT, MCHC of erythrocytes, CWS-A II group was increased compared to controls. In histological observations, CWS-A II group was observed synoviocytes more than control group and was observed proteoglycans in the deep layers. Conclusion : The data suggest that CWS-A significant anti-arthritic effects that may be mediated by suppressing inflammatory parameters.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.11-23
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• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.155-162
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• 1999

This study was performed to assess that clinco-therapeutic effect of natural Italian honeybee (Apis mellifera) venom in adjuvant-induced arthritic rat. Ninety Sprague- Dawley rats of male were injected with complete Freund's adjuvant (CFA). Adjuvant arthritis was produced by a single subcutaneous injection of 1 mg Mycobacterium butyricum suspended in 0.1 ml paraffin oil into the right hindpaw. Righting reflex was uniformly lost and considered to be the point of arthritis development on day 14 after CFA injection. Experimental groups were divided into three groups. When arthritis was developed in the rat hind-paw, tested groups were administrated with prednisolone (10 mg/kg, p.o) and honeybee venom (one bee, s.c) at an interval of two days. Control group was subcutaneously injected with 0.1 ml of physiological saline solution in the rat at an interval of two days. Clinical findings, hematological values and histopathological findings were observed during or after the drugs administration. In tested groups, the development of inflammatory edema and polyarthritis on day 14 after treatment was suppressed. No significant differences of hindpaw edema volume and lameness score between prednisolone and honeybee venom groups were observed during or after therapeutic drugs treatment. WBC counts of prednisolone and honeybee venom treatment groups as compared with the control group were getting remarkably decreased during or after the therapeutic drugs administration(p＜0.01). Erosions of articular cartilage and inflammatory cell infiltrations during or after the therapeutic drugs treatment was effectively suppressed in natural honey venom.

• Journal of Korean Medicine Rehabilitation
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• v.21 no.1
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• pp.79-95
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• 2011

Objectives : This study was to investigate the antiarthritic effect of Hwallak-dan(Huoluo-dan) on the complete freund's adjuvant(CFA)-induced arthritis in Lewis rats. Methods : Arthritis was induced by intradermal injection of CFA into base of tail. Experimental groups divided into normal(n=10), control(n=10) and treated(n=10) group. Animals of control group received normal saline for twenty days, treated group received extracts Hwallak-dan(Huoluo-dan) for same duration, light mineral oil only injected non-arthritic rats were served as normal group. The incidence of arthritis and arthritic index were observed after treatment. Body weight, paw edema volume and thickness of ankle joint were measured at 0, 11, 14, 17, 20 days after treatment. White blood cell(WBC) counts in blood were analysed at 20 days after treatment and tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta}$), IL-6 contents in paw exudate were analysed by ELISA at 20 days after treatment. Histopathology on the ankle joint were performed at 20 days after treatment. Results : 1. Incidence of arthritis of treated group was 60% and control group was 100% at 20 days after treatment. 2. Arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. 3. Paw edema volume and thickness of ankle joint of treated group was significantly decreased compared with control group at 20 days after treatment. 4. Total WBC of treated group was significantly decreased compared with control group at 20 days after treatment. 5. Neutrophils of treated group was significantly decreased compared with control group at 20 days after treatment. 6. $TNF-{\alpha}$ content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 7. $IL-1{\beta}$ content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 8. IL-6 content content in paw exudate of treated group was significantly decreased compared with control group at 20 days after treatment. 9. Histopathological arthritic index of treated group was significantly decreased compared with control group at 20 days after treatment. Conclusions : These results indicate that Hwallak-dan(Huoluo-dan) has inhibitory effect on the development and progression of CFA-induced arthritis in rats.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.2
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• pp.138-151
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• 2003

Although the use of acupuncture for pain has increased in recent years, the mechanisms of acupuncture analgesia (AA) remains obscure. The lack of suitable experimental animal models for persistent pain, which show clear AA, has been the major stumbling block in the investigation of the physiological mechanisms of AA. In the present study, we test AA in two knee arthritis model induced by injection of CFA or carrageenan as a chronic pain model. After induction of arthritis, the rat subsequently showed a reduced stepping force of the affected limb for the next several days. Electroacupuncture (EA) was applied to an acupuncture point each on the contralateral forelimb for 30 minutes under enflurane anesthesia. After the termination of EA, behavioral tests measuring stepping force were periodically conducted during the next several hours. EA produced a significant improvement of stepping force of the foot lasting for at least 2 hours when applied to LR2 In CFA model, and applied to ST36 in carrageenan model, but both points did not produce any significant effects in each other model. These data suggest that EA produce analgesic effect in knee arthritic pain and the analgesic effect is specific to the acupuncture point.

• Journal of Pharmacopuncture
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• v.26 no.3
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• pp.257-264
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• 2023

Objectives: The study was designed to evaluate anti-arthritic activity of Ajmodadi Churna (AC) and its effect on Complete freund's adjuvant (CFA)-induced arthritis in Wistar rats. Methods: Arthritis was induced by injecting 0.2 mL CFA into sub plantar surface of left hind paw. Test sample AC-1 and AC-2, 200 and 400 mg/kg, respectively was given to the animals for 21 consecutive days. The increase in swelling was observed after induction of arthritis. The paw edema was measured on 0, 3, 7, 14 and 21 day using Vernier caliper after the induction of arthritis. The collected blood samples further used for the estimation of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb), using hematology analyzer. Serum concentration of IL-6 and TNF-α were also measured using rat ELISA kits. Results: Results showed that a significant reduction in paw edema was observed in AC-2 treated rats. The paw edema was restored on day 21 was 4.48 mm for AC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.83 for AC-2 and 1.50 for AC-1. A decrease in levels of RBC and hemoglobin were observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug. Conclusion: It can be concluded from the study that AC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.124-132
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• 2002

Daebangpung-tang(DBPT) is one of the prescriptions used for the treatment of rheumatoid arthritis(RA) in oriental medicine. The present study aimed to examine the analgesic effect of DBPT on a rat model of CFA-induced arthritis, which is not identical to human auto-immune arthritis although it does have many features in common with RA, and the relation between DBPT-induced analgesia and steroid hormones. CFA-induced arthritis rat model used to test the effect of DBPT was chronic pain model. After the induction of arthritis, rats subsequently showed a reduced stepping force of the affected limb for at least the next 18 days. The reduced stepping force of the limb was presumably due to a painful knee, since oral injection of indomethacin produced temporary improvement of weight bearing. DBPT dissolved in water was orally administrated. After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 4 hours. DBPT produce significant improvement of stepping force of the hindlimb affected by the arthritis lasting at least 3 hours. The magnitude of this improvement was equivalent to that obtained after an oral injection of 3mg/kg of indomethacin and this improvement of stepping force was interpreted as an analgesic effect. The reduced stepping force was divided into three stages(10-30g, 30-50g, and 50-70g). All experiments was performed at 50-70g of stepping force, since both DBPT and indomethacin showed the most excellent analgesic effect at 50-70g of stepping force. DBPT produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner and showed analgesic effect on neuropathic pain as well. DBPT-induced analgesic effect could not be blocked by systemic injection of steroid antagonist mifepristone. The present study suggest 1) that DBPT produces a potent analgesic effect on the chronic knee arthritis pain model in the rat and 2) that steroids system does not mediate DBPT-induced analgesia.

• Journal of Acupuncture Research
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• v.20 no.2
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• pp.85-97
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• 2003

Introduction : In this study, the analgesic effect and its mechanism of bee venom aqua-acupuncture on complete Freund's adjuvant-induced arthritis in rats was investigated. It has been reported from a neurochemical standpoint that bee venom exerts antinociceptive effects on inflammation and that the opioid system and adrenergic system play important roles in acupuncture analgesia. however, it is not known whether central opioid and ${\alpha}2$-adrenergic components of the intrinsic descending analgesic system are activated after bee venom aqua-acupuncture. Methods : Bee venom(1mg/kg) was subcutaneously aqua-acupunctured into Joksamni($ST_{36}$) of rats with complete Freund's adjuvant(CFA)- induced arthritis and was checked of increase in TFL. Opioid and ${\alpha}_2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist, and yohimbine as ${\alpha}_2$-adrenoceptor antagonist prior to bee venom aqua-acupuncture. Results : The following results have been obtained. 1. The tail flick latency in the rat model with adjuvant-induced arthritis was significantly decreased in 2 weeks. 2. The tail flick latency in the rat model with adjuvant-induced arthritis was increased in bee venom aqua-acupuncture group compared to the normal saline aqua-acupuncture group. 3. Analgesic effect of bee venom was antagonized by yohimbine not by naloxone pretreatment in the rat model adjuvant-induced arthritis. Conclusions : Bee venom aqua-acupuncture has an analgesic effect on the rat model of adjuvant-induced of adjuvant-induced arthritis and has antinociception mediated by ${\alpha}_2$-adrenergic system.

• Reproductive and Developmental Biology
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• v.35 no.2
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• pp.151-157
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• 2011

Clinical arthritis is typically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Arthritis-induced muscle weakness is a major problem in aged people, leading to a disturbance of balance during the gait cycle and frequent falls. The purposes of the present study were to confirm fiber type-dependent expression of muscle atrophy markers induced by arthritis and to identify the relationship between clinical signs and expression of muscle atrophy markers. Mice were divided into four experimental groups as follows: (1) negative control (normal), (2) positive control (CFA+acetic acid), (3) RA group (CFA+acetic acid+type II collagen), and (4) aging-induced OA group. DBQA/1J mice (8 weeks of age) were injected with collagen (50 ${\mu}g/kg$), and physiological (body weight) and pathological (arthritis score and paw thickness) parameters were measured once per week. The gastrocnemius muscle from animals in each group was removed, and the expression of muscle atrophy markers (MAFbx and MuRF1) and myosin heavy chain isoforms were analyzed by reverse transcription-polymerase chain reaction. No significant change in body weight occurred between control groups and collagen-induced RA mice at week 10. However, bovine type II collagen induced a dramatic increase in clinical score or paw thickness at week 10 (p<0.01). Concomitantly, the expression of the muscle atrophy marker MAFbx was upregulated in the RA and OA groups (p<0.01). A dramatic reduction in myosin heavy chain (MHC)-$I{\beta}$ was seen in the gastrocnemius muscles from RA and OA mice, while only a slight decrease in MHC-IIb was seen. These results suggest that muscle atrophy gene expression occurred in a fiber type-specific manner in both RA- and OA-induced mice. The present study suggests evidence regarding why different therapeutic interventions are required between RA and OA.

• Korean Journal of Oriental Medicine
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• v.12 no.3 s.18
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• pp.49-58
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• 2006

Although the usage of acupuncture for pain has increased in recent years, the mechanisms of acupuncture analgesia (AA) remain unclear. The lack of suitable experimental animal models for persistent pain, which show clear AA, has been the major stumbling block in the investigation of the physiological mechanisms of AA. In the present study, we test AA in two knee arthritis models induced by injection of CFA or carrageenan as persistent pain models. After induction of arthritis, the rat subsequently showed a reduced stepping force of the affected limb for the next several days. Electroacupuncture (EA) was applied to an acupuncture point each on the contralateral forelimb for 30 minutes under gaseous anesthesia. After the termination of EA, behavioral tests measuring stepping force were periodically conducted during the next several hours. EA produced a significant improvement of stepping force of the foot lasting for at least 2 hours when applied to LR2 in CFA model, and applied to ST36 in carrageenan model, but both points did not produce any significant effects in each other model. Further experiments showed that intraperitoneal pretreatment of naltrexone, a non-selective opioid antagonist, did not reduced the EA-induced improvement of stepping force in both of two models. These data suggest that EA produce analgesic effect in knee arthritic pain and the analgesic effect is specific to the acupuncture point depending on painful conditions.