• The Korean Journal of Pain
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• v.12 no.2
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• pp.171-176
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• 1999

Background: Effect of nitric oxide on the hyperalgesia induced by inflammation is controversial. From our previous experiment, NOS inhibitor, L-NAME given during the induction period decrease mechanical hyperalgesia occured by Freund's complete adjuvant induced inflammation. In addition, we attempted to analyze the effects of L-NAME on mechanical hyperalgesia after the development of inflammation by Freund's complete adjuvant in rat paw. Methods: Male Sprague Dawley rats were divided into four groups; control (normal saline), and three different doses of L-NAME (0.1 mg, 1 mg, 10 mg). Inflammation was induced in rats by injecting 0.15 ml of Freund's complete adjuvant (FCA) intraplantarly. Rats showed typical hyperalgesia within twelve hours after injection and maintained this for about one week. Tests were done 2 days after injection of FCA. After the baseline test either L-NAME or saline was injected under light halothane anesthesia. Effect of L-NAME on hyperalgesia was assessed by measuring mechanical hyperalgesia at 15, 30, 60, 90, 120 minutes. Same experients were repeated on normal rats. Results: When injected at the site of inflammation, L-NAME caused dose dependent decrease in mechanical hyperalgesia. However, normal rats also showed increased mechanical threshold after L- NAME injection. Conclusions: Although L-NAME reduces FCA induced mechanical hyperalgesia, this result may solely be due to inhibition of nitric oxide production and need to be further determined.

• Food Science and Biotechnology
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• v.14 no.2
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• pp.228-232
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• 2005

The effect of a potato ethanol extract was investigated on Freund's complete adjuvant (FCA)-induced arthritis. The oral administration of the potato extract, at doses of 100 and 200 mg/kg once a day for 21 days, significantly reduced hindpaw swelling and the production of inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6). Treatment with the potato extract also decreased the plasma levels of creatinine, triglyceride and LDL-cholesterol, and the activities of AST and ALT compared with those of a control group. These results suggest that the potato extract might be beneficial in the treatment of chronic inflammatory disorders.

• The Korean Journal of Pain
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• v.11 no.2
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• pp.194-200
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• 1998

Background: Effect of nitric oxide on the hyperalgesia induced by inflammation is controversial. We attempted to find out the peripheral effects of nitric oxide (NO) on hyperalgesia induced by Freund's complete adjuvant (FCA) induced inflammation. Methods: Male Sprague Dawley rats were divided into three groups; control, low dose NG-nitro-L-arginine methyl ester (L-NAME, 500 ug), high dose L-NAME (5 mg). Inflammation was induced by injecting 0.1 ml of FCA intraplantarly, which shows typical hyperalgesia within twelve hours after injection and maintained for about one week. Drugs were injected 2 hours before, just before, and 3, 6, 9, 12 hours after the injection of FCA. Effect of L-NAME on hyperalgesia was assessed by measuring mechanical hyperalgesia and spontaneous pain for 3 days. Results: When injected at the site of inflammation, L-NAME caused dose dependent reduction of spontaneous hyperalgesia. Mechanical hyperalgesia was also reduced by high dose L-NAME (p<0.05). After systemic injection of high dose L-NAME in the back, no significant difference was noticed. Conclusions: This suggest that L-NAME reduces FCA induced hyperalgesia via peripheral action.

• 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.

• Herbal Formula Science
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• v.16 no.2
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• pp.115-131
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• 2008

실험목적 : 빈소산은 11가지 생약으로 구성된 복합 한약 처방으로 관절염을 포함한 다양한 염증성 질환의 치료제로 사용되어 왔으나, 관절염에 대한 직접적인 효력평가는 찾아 보기 힘들다. 따라서 본 실험에서는 빈소산 추출물이 Freund's complete adjuvant (FCA)로 유발된 rat 류마티스성 관절염에 미치는 치료 효과를 dexamethasone (15mg/kg, 복강 투여) 의 효과와 비교 평가하였다. 실험방법 : 류마티스성 관절염은 FCA (10mg in 1ml paraffin oil 0.1ml/rats)를 좌측 후지에 피내 투여하여 유발하였다. 실험동물은 Wistar 랫트를 사용하였고, FCA 투여 14일 후 유사한 무릎관절 둘레를 나타내는 류마티스성 관절염 유발 rat와 정상 rat 및 실험군을 그룹당 9마리씩 나누었다. 실험동물은 100 또는 200mg/kg의 빈소산 추출물을 FCA 투여 14일 후부터 14일간 경구 투여하였으며, dexamethasone은 15mg/kg 농도로 복강 투여한 다음, 희생하여, 체중, 연골내 collagen 함량 및 chondroitin sulphate, heparin sulphate 및 hyaluronic acid와 같은 뼈내 glycosaminoglycan 함량의 변화를 각각 관찰하였다. 실험결과는 항염 효과가 이미 입증되어 있는 dexamethasone 15mg/kg 복강 투여군과 비교하였다. 결과 : FCA 투여는 현저한 체중, 연골내 collagen 함량 및 chondroitin sulphate, heparin sulphate 및 hyaluronic acid와 같은 뼈내 glycosaminoglycan 함량의 감소와 함께 유발 관절 둘레 및 조직내 prostaglandin $E_2$의 증가와 같은 전형적인 류마티스성 염증을 초래하였으나, 이러한 류마티스성 관절염 소견은 dexamethasone 및 모든 용량의 빈소산 추출물 투여에 의해 현저히 억제되었으며, 특히 빈소산 투여군에서는 투여 용량 의존적인 감소가 인정되었다. 결론 : 이상에서 빈소산 추출물은 투여 용량 의존적인 prostaglandin $E_2$ 억제를 매개하여 FCA 유발 류마티스성 관절염에 대한 치료 효과를 나타내는 것으로 관찰되었다. 따라서 새로운 관절염에 대한 치료제로서 개발 가능성이 있을 것으로 판단된다. 한편 빈소산 추출물은 주로 prostaglandin $E_2$ 억제작용에 의해 항염 효과를 나타내는 것으로 관찰되었으나, 금후 다른 작용기전에 대한 연구와 빈소산의 구성성분 중 유효 성분 규명을 위한 실험이 수행되어야 할 것으로 판단된다.

• Journal of fish pathology
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• v.5 no.1
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• pp.19-27
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• 1992

A formalized bacterin(FKC) of Edwardsiella tarda, conjugated with/without Freund's complete adjuvant(FCA), Freund's incomplete adjuvant(FIA) and potassium aluminium sulfate(PAS), was administered by intraperitoneal injection to tilapia respectively. The tilapia were reared under indoor recirculating filter system. There were agglutinin titer increment in the tilapia which were administered not only FKC bacterin but also adjuvanted vaccines. But the producing time of the highest level of antibody in the immunized tilapia was different among vaccine preparation, i. e. FKC+FCA group and PAS+FKC group are between the 2nd and the 4th week, and FKC alone group is the 2nd week. In the challenge experiment with $2.5{\times}10^7\;CFU/ml$ or $2.5{\times}10^8\;CFU/ml$ of E. tarda T1123 to the tilapia immunized with vaccines, RPS above sixty was recorded both challenge dose in the tilapia which were 3 weeks after immunization with FKC+FCA, PAS+FKC and FKC alone, and the former dose 8 weeks after immunization with FCA+FKC and PAS+FKC. There were some resistance enhancement against E. tarda in the tilapia which were injected with adjuvant alone than that of control. As the results, the FCA or PAS adjuvanted vaccine is effective to sustain the defensible period against edwardsiellosis.

• Journal of Acupuncture Research
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• v.18 no.2
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• pp.27-36
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• 2001

Objectives : In order to study the effects of Harpagophyti Radix Aqua -acupuncture in rats with arthritis induced by Freund's complete adjuvant, performed several experimental items : that is edema rate, number of WBC, hemazocrit, platelet, total protein and albumin. Methods : In this study rats were divided into five groups : Normal group (non treated group), Control group (non-injected group in rats with arthritis induced by FCA), ST group (0.2cc normal Saline-injected group at right Chok-Samni(Zusanli,$ST_{36}$) once in every two days during the two weeks in rats with arthritis induced by FCA), HRS group (0.2cc Harpagophyti Radix-subcutaneous injected group once in every two days during the two weeks in rats with arthritis induced by FCA), HRST group (0.2cc Harpagophyti Radix-injected group at Chok-Samni($ST_{36}$) once in every two days during the two weeks in rats with arthritis induced by FCA). Results : 1. In the right plantar edema, HRS group showed a decrease with statistical significance on the 2 weeks and HRST group showed a decrease with statistical significance on the 1 weeks as compared with control group. 2. In the WBC, HRST group showed a meaningful decrease with statistical significance and also HRS group showed a decrease with statistical significanae as compared with control group. 3. In the platelet, HRST group showed a decrease with statistical significance as compared with control group. 4. In the hematocrit, HRS group showed a increase with statistical significance as compared with control group. 5. In the serum total protein and albumin, HRS group showed a increase with statistical significance as compared with control group. Conclusions : According to the above result, it is concluded that Harpagophyti Radix Aqua-acupuncture showed the therapeutic effect of antiinflammation in adjuvant arthritis and it is suggested that further studies and researchs for clinical use be needed.

• 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.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.3
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• pp.1-14
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• 2013

Objectives The object of this study was to observe the favorable anti-arthritic effects of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) on Freund's complete adjuvant (FCA)-induced arthritic Wistar rats. Methods Rheumatoid arthritis was induced by intradermal injection of FCA, and 300, 150 or 750 mg/kg of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 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. All rats were sacrificed at 14 days after continuous oral treatment of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) or intraperitoneal administration of dexamethasone, and 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 compositions - chondroitin sulphate, heparan 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, heparan sulphate and hyaluronic acid contents, with increases on the knee circumferences, gross arthritis scores and inflammatory tissue $PGE_2$ levels. However, these changes from FCA-induced rheumatoid arthritis were clearly reduced by treatment of dexamethasone and both two different dosages of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 and 150 mg/kg in the present study. Although FCA-induced arthritis were more favorably inhibited by treatment of dexamethasone 15 mg/kg as compared with Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg, marked decreases of body weights were detected in dexamethasone 15 mg/kg treated rats, and Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg showed similar preserve effects on the cartilage glucosaminoglycan compositions in this study. Conclusions The results obtained in this study suggest that over 300 and 150 mg/kg of Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) showed favorable anti-arthritic effects on the FCA-induced arthritis mediated by suppression of $PGE_2$, a inflammatory mediator. However, detail mechanism studies should be conduced in future with the screening of the biological active compounds in this herb. Although overall anti-inflammatory effects Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg were lowered than those of dexamethasone 15 mg/kg treated rats, Samki-eum ($s\bar{a}nq\grave{i}-y\check{i}n$) 300 mg/kg treated rats showed similar preserve effects on the cartilage glucosaminoglycan compositions in this experiment.

• Journal of Pharmacopuncture
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• v.14 no.4
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• pp.23-32
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• 2011

Objectives: This study was performed to examine the antigenic potential of pure melittin (Sweet Bee Venom - SBV) extracted from the bee venom by utilizing protein isolation method of gel filtration. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea), authorized a non-clinical studies institution, under the regulations of Good Laboratory Practice (GLP). Antigenic potential of SBV was examined by active systemic anaphylaxis (ASA) and passive cutaneous anaphylaxis (PCA) in guinea pigs. SBV was subcutaneously administered at 0.07 and 0.28mg/kg and also as a suspension with adjuvant (Freund's complete adjuvant: FCA). Ovalbumin (OVA) as a suspension with adjuvant was used to induce positive control response ($5mg/m{\ell}$-FCA). Results: 1. In the ASA test, experimental groups showed some symptoms of anaphylaxis like piloerection, hyperpnea and staggering gait. 2. In the PCA test, low dosage group did not show any antibody responses, whereas high dosage group showed positive responses. 3. In the weight measurement and clinical observation, experimental groups didn't show any significant changes compared with control group. 4. In the autopsy of body, the abnormalities of lung were detected in the corpse. This means that the cause of death may induced anaphylactic shock. Conclusions: Above findings suggested that SBV had antigenic potential in guinea pig. Further studies on the subject should be conducted to yield more concrete evidences.