• Biomolecules & Therapeutics
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• 제28권5호
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• pp.414-422
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• 2020

Fangchinoline (FAN) is a bisbenzylisoquinoline alkaloid that is widely known for its anti-tumor properties. The goal of this study is to examine the effects of FAN on arthritis and the possible pathways it acts on. Human fibroblast-like synovial cells (FLS), carrageenan/kaolin arthritis rat model (C/K), and collagen-induced arthritis (CIA) mice model were used to establish the efficiency of FAN in arthritis. Human FLS cells were treated with FAN (1, 2.5, 5, 10 µM) 1 h before IL-1β (10 ng/mL) stimulation. Cell viability, reactive oxygen species measurement, and western blot analysis of inflammatory mediators and the MAPK and NF-κB pathways were performed. In the animal models, after induction of arthritis, the rodents were given 10 and 30 mg/kg of FAN orally 1 h before conducting behavioral experiments such as weight distribution ratio, knee thickness measurement, squeaking score, body weight measurement, paw volume measurement, and arthritis index measurement. Rodent knee joints were also analyzed histologically through H&E staining and safranin staining. FAN decreased the production of inflammatory cytokines and ROS in human FLS cells as well as the phosphorylation of the MAPK pathway and NF-κB pathway in human FLS cells. The behavioral parameters in the C/K rat model and CIA mouse model and inflammatory signs in the histological analysis were found to be ameliorated in FAN-treated groups. Cartilage degradation in CIA mice knee joints were shown to have been suppressed by FAN. These findings suggest that fangchinoline has the potential to be a therapeutic source for the treatment of rheumatoid arthritis.

• 대한본초학회지
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• 제28권6호
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• pp.87-93
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• 2013

Objectives : Degenerative arthritis arises from several physiological factors. The purpose of this study is to investigate the beneficial effects of Phyto-extract Complex (CME) on degenerative arthritis. Methods : CME is composed of extracts of mulberry (Morus alba L.) fruit, mulberry leaves and black beans (Glycine max (L.) Merr.). To measure the toxicity of CME, we performed the single-dose toxicity study. For the evaluation of its effects on degenerative arthritis, we examined the inhibition of cyclooxygenase-2 (COX-2) activity, using in vitro enzyme activity assay, the reduction of protein expression of COX-2, 5-lipoxygenase (5-LO), and inducible nitric oxide synthase (iNOS) in RAW264.7 cells which were stimulated by lipopolysaccharide (LPS). We also examined the serum level of prostaglandins (PGs) and injury of the knee joint cartilage, using animal model of degenerative arthritis induced by mono-sodium iodoacetate (MIA). Results : CME did not have any toxicity in single-dose toxicity study. The CME inhibited the activity of COX-2 and could reduce the protein expression of COX-2, 5-LO and iNOS in RAW264.7 cells. The CME also reduced the serum level of PGs and prevented from the cartilage injury of knee joint in animal model of degenerative arthritis induced by MIA. Conclusions : Taken altogether, the CME could be useful for the improvement of degenerative arthritis through its various anti-inflammatory activities and prevention from the cartilage injury of knee joint.

• 생명과학회지
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• 제31권8호
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• pp.736-744
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• 2021

강화사자발쑥(Artemisia princeps Pampanini)은 항산화, 항염증 및 항균제와 같은 면역 기능 관련 질병에 널리 사용되는 약초이다. 이 연구에서 우리는 RAW 264.7 세포에서 AP 추출물의 항염증 효과를 조사하고 관련 메커니즘을 평가하였다. AP 추출물의 효과는 complete Freund's adjuvant (CFA) 유도 관절염 및 lipopolysaccharide(LPS) 유도 마우스 모델에서도 평가되었다. RAW 264.7 세포에서 AP 추출물은 LPS에 의해 유도 된 산화질소(NO) 생성과 inducible NO synthase 및 cyclooxygenase-2 단백질 발현을 현저하게 억제했다. RAW 264.7 세포에서 LPS로 유도된 mitogen-activated protein kinase 와 nuclear factor-κB의 인산화 또한 AP 추출물에 의해 유의하게 억제되었다. AP 추출물의 경구 투여는 CFA 처리 마우스 그룹에 비해 발의 부종 및 비장 지수 증가를 억제하였다. 조직학적으로 CFA 처리 마우스 군에서는 cartilage와 synovium에서 염증 세포의 침윤이 증가한 반면 AP 추출물 투여군에서는 억제되었다. 더욱이, AP 추출물은 염증성 사이토카인으로 알려진 tumor necrosis factor-α 수준을 CFA 및 LPS 처리 마우스 모델에서 현저하게 감소시켰다. 결론적으로, AP 추출물의 항염증 및 항 관절염 효과는 in vitro 및 in vivo 모델 모두에서 확인되었으며, 이는 Artemisia princeps Pampanini가 관절염 치료의 후보 물질이 될 수 있음을 시사한다.

• 동의생리병리학회지
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• 제22권3호
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• pp.542-547
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• 2008

In order to examine anti-inflammatory effect of Cinnamomi Ramulus (CR) alcohol extract on rheumatoid arthritis, the present study investigated the viability and TNF-${\alpha}$ production in Raw264.7 cells treated with CR and collagen induced arthritis in DBA/1J mice which were orally administered with CR prior to immunization. The results are as follows: CR extract at $20{\mu}g/ml$ inhibited the viability of Raw264.7 by 50%. CR at 15 and $20{\mu}g/ml$ showed a significant decrease in TNF-${\alpha}$ levels from Raw264.7 cells treated with LPS. CR administration decreased arthritic index in DBA/1J mice immunized with bovine collagen type II but it did not reach statistical significance. CR administration significantly decreased spleen weights obtained from mice in 6 weeks after immunization. CR administration significantly decreased serum anti-type II collagen antibody levels compared with control group. CR administration decreased serum IL-6 levels compared with control group but it did not reach statistical significance.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.453-462
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• 2020

Chronic joint pain due to loss of cartilage function, degradation of subchondral bone, and related conditions are common plights of an arthritis patient. Antioxidant compounds could solve the problems in arthritic condition. The objective of this study was to evaluate the anti-arthritic activity of D-carvone against complete Freund's adjuvant (CFA)-induced arthritis in rats. D-carvone was orally administered for 25 days at the doses of 30 and 60 mg/kg against CFA-induced arthritic rats. Changes in body weight, paw swelling, organ index, hematological parameters, oxidative stress markers, inflammatory cytokines, and histopathology were recorded. Oral treatment of D-carvone significantly improved the body weight, reduced the paw swelling, edema formation, and organ index in arthritic rats. The levels of white blood cells were reduced, red blood cells and hemoglobin levels were improved in D-carvone treated arthritic rats. Lipid peroxidation levels were lowered whereas enzymatic and non-enzymatic antioxidants were significantly elevated by D-carvone administration against arthritic rats. D-carvone significantly modulated inflammatory cytokine levels and improved the ankle joint pathology against CFA-induced arthritic inflammation. In conclusion, D-carvone proved significant anti-arthritic activity against CFA-induced arthritis in rats.

• 한방재활의학과학회지
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• 제15권1호
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• pp.127-141
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• 2005

Objectives : This study was performed to investigate the effects of Gamichangbaek-san(Jiaweichangbai-san) on anti-inflammatory, analgesic, anti-febrile and immune response on the arthritis of carrageenan-induced animals. Methods and Materials : Rats were classified into control and sample groups which are 7 individuals each for the experiments about anti-inflammatory and anti-febrile. Each of the 7 mice were classified into normal, control, sample groups for the analgesic experiments. Gamichangbai-san(Jiaweichangbai-san) was administered to sample group and normal saline was administered to normal and control groups. Arthritis was induced by injection of 1% carrageenan $0.1m{\ell}$ and Gamichangbaek-san(Jiaweichangbai-san) was administered after 30 minutes. The change of edema in Carrageenan-induced Arthritic Rats' Paws was measured after 1 hour and 5 hours from the injection of carraqeenan with Plethysmometer(7150, UGO BASILE, ltaly) by Winter' method. WBC, Lymphocyte and ESR were measured by heart puncture and CD4+ T cell, CD8+ T cell and CD4+/CD8+ T cell ratio were measured from the spleen tissue. Writhing syndrom was measured with Tail flick unit(UGO BASILE, Italy) in the experiments conducted to check the analgesic activity. The temperature of the paws of carrageenan-induced arthritic rats was measured by Laser thermometer. Rectal temperature was measured by Yeast's method in anti-febrile experiments. Immune response was measured by CD4+, CD8+ T cell ratio and CD4+/CD8+ T cell ratio. Results : 1. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased the increase rate of Paw Edema effectively with statistical significance. 2. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased WBC, Lymphocyte and ESR with statistically high significance. 3. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) did not show significant analgesic effect, but the Pressure pain threshold of the paws was increased with statistical significance. 4. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased rectal temperature effectively and had an anti-febrile effect about the febrile of a joint with statistical significance. 5. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) increased CD4+ T cell ratio with statistically high significance and increased CD+8 T cell ratio with statistical non significance but increased CD4+/CD8+ T cell ratio effectively with statistical significance, too. Conclusions : According to the above results, it can be concluded Gamichangbaek-san(Jiaweichangbai-san) showed the treatment effects on the artificial arthritis resulted from carageenan in rats and it is suggested that more interest and study in the security for the clinical use were needed.

• Journal of Periodontal and Implant Science
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• 제48권6호
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• pp.347-359
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• 2018

Purpose: Periodontitis and rheumatoid arthritis (RA) share a similar inflammatory pathogenesis. Porphyromonas gingivalis (Pg) can induce anticyclic-citrullinated peptide autoantibodies (anti-CCP antibodies), a key factor in the development of RA. This study aimed at evaluating the relationships between the 2 diseases and identifying the clinical implications thereof, with a focus on periodontal pathogens in Korean adults. Methods: A total of 260 RA patients and 86 age- and sex-matched control patients without arthritis were enrolled in this prospective cross-sectional study. Periodontal indices and the prevalence and amount of periodontal pathogens were compared between the groups. Correlations between periodontal and RA indices were examined, as were correlations between 9 periodontal pathogens and RA indices. Results: The RA group had significantly higher values than the control group for all investigated periodontal indices (P<0.05) except the number of teeth. The gingival index (GI) was correlated with the disease activity score 28 (DAS28) (r=0.125, P=0.049), RA disease duration (r=0.253, P<0.001), erythrocyte sedimentation rate (ESR) (r=0.162, P=0.010), and anti-CCP antibody titer (r=0.205, P=0.004). Probing pocket depth (PPD) was correlated with ESR (r=0.139, P=0.027) and anti-Pg antibody titer (r=0.203, P=0.001). Bleeding on probing (BOP) was correlated with DAS28 (r=0.137, P=0.030), RA disease duration (r=0.202, P=0.001), ESR (r=0.136, P=0.030), anti-Pg antibody titer (r=0.177, P=0.005), and anti-CCP antibody titer (r=0.188, P=0.007). Clinical attachment level (CAL) and periodontitis severity were correlated with anti-Pg antibody titer (the former r=0.201, P=0.002; the latter r=0.175, P=0.006). The quantity of Pg was positively correlated with the serum anti-Pg antibody titer (r=0.148, P=0.020). Conclusions: The GI, BOP, and PPD showed positive relationships with several RA indices. The anti-Pg antibody titer had positive relationships with PPD, BOP, CAL, and periodontitis severity. Thus, increasing values of periodontal indices could be used as a risk indicator of disease development in RA patients, and an increasing anti-Pg antibody titer could be considered as a warning sign in RA patients suffering with periodontitis.

• 한국약용작물학회지
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• 제17권6호
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• pp.470-474
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• 2009

Achyrantes japonica (AJ) has been used to treat edema and arthritis in the traditional Korean medicine. To elucidate the anti-inflammatory and anti-nociceptive effects of ethanol extract of AJ, the carrageenan-induced paw edema using a plethysmometer and thermal hypersensitivity using the plantar test were measured. Ibuprofen was used as a control drug. Treatment with AJ (200mg/kg p.o.) significantly reduced paw edema, compared to the carrageenan - treated rats. In the plantar test, the thermal withdrawal latency in AJ - treated group was significantly increased than the carrageenan - treated group. The results indicate that AJ could have be the anti-inflammatory and anti-nociceptive properties.

• 디지털융복합연구
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• 제14권1호
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• pp.353-361
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• 2016

본 연구는 독활의 기능을 부가시키고자 발효과정을 통해 융합-발효 추물물을 얻어 항염증효과를 확인 하고자 한다. 독활을 이용하는데 한계가 있어 유산균주들을 활용한 발효과정을 통해 이용 가능한 균주를 선별하고, 독활의 열수 추출물과 비교하여 총 폴리페놀, 아미노산 총량, 주요 생리활성 미네랄 성분 분석 결과 발효과정을 통해 증가함을 확인하였다. 독활의 발효추출물의 항염증 효과를 확인하고자 관절염 염증반응과 관련된 사이토카인들을 측정하였고, 관절염시 주로 동반되는 연골조직 파괴를 억제 효능을 평가하기 위해 MMP-9 활성도를 확인하였다. 이러한 결과들은 유산균을 이용한 발효과정을 통해 독활의 주요 생리활성이 증가하고 염증반응 억제 효과도 증가하는 것으로 보여진다. 이 연구는 독활의 관절염 예방적 효과를 연구하는데 있어 기초 연구가 될 것으로 기대된다.

• Journal of Acupuncture Research
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• 제25권3호
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• pp.95-106
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• 2008

Objectives : This study is to evaluate Effect of Hong Hua Za acupuncture anti-inflammatory on rheumatoid arthritis that caused by Lipopolysaccharide in mouse. Methods : Hong Hua Za(Carthami Tinctorii Fructus) acupuncture(HA) was prepared and tested for therapeutic potential of rheumatoid arthritis, by measuring the inhibition of inducible nitric oxide synthase (iNOS) expression, nitric oxide(NO) production in vitro experiment, by measuring Tumpr Necrosis Factor-$\alpha$(TNF-$\alpha$) & Nuclear Factor kappa B(NF-$\kappa$B) p65 activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice. Results : HA showed therapeutic effects on Lipopolysaccharide(LPS)-induced rheumatoid arthritis. HA inhibited iNOS mRNA and NO in RAW264.7cell of LPS-induced rheumatoid arthritis in a dose dependent manner. HA also showed significant inhibition of TNF-$\alpha$ & NF-$\kappa$B p65, activation, synovial hyperplasia, angiogenesis and fibrosis in synovial membrane of knee joint of mice. Conclusions : These results suggest that HA has an therapeutic effects on LPS induced-rheumatoid arthritis by inhibiting TNF-$\alpha$ activation.