• 동의생리병리학회지
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• 제22권2호
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• pp.390-396
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• 2008

Osteoarthritis(OA) diseases are characterized by joint pain, tenderness, limitation of movement, crepitus, occasional effusion, and variable degrees of inflammation without systemic effects. We investigated the effects of Achyrantis radixs cream treatment and low intensity ultrasound in monosodium iodoacetate(MIA) induced experimental osteoarthritis rat. Sprague-Dawley 40 rats of 7-8 weeks, weight $250\;{\pm}\;50$ g were divided into four groups including the control group and ostoarthritis group(30 rats). Histopathological examination, Mankin's score, and immunohistochemical were performed. Histological findings in control group that are similar to those observed in human osteoarthritis, such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure. Safranin O-fast green staining revealed that marked diffuse reduction of proteoglycans and chondrocyte treated with MIA. The Mankin's score were closely correlated to the grade of histological findings. The level of Bax and caspase-3 expression decreased experimental groups. This study shows that a Acyranthes Radix cream treatment and low intensity ultrasound exerts a beneficial influence on the severity of chondral lesion in osteoarthritis rats. This treatments could related to a reduced level of chondrocyte apoptosis through anti-apoptotoc capacities of MIA-induced apoptotic protein overexpression.

• 한국약용작물학회지
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• 제21권6호
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• pp.466-473
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• 2013

This study investigates the effect of supercritical fluid extract (CMPB803-C) of Lithospermum erythrorhizon, shikonin and acetylshikonin isolated from Lithospermum erythrorhizon on IL-$1{\beta}$-induced chondrocytes and monosodium iodoacetate (MIA)-induced osteoarthritis in rat. Shikonin ($50{\mu}m$) and acetylshikonin ($3{\mu}M$) treatment reduced significantly the mRNA expression and enzyme activity of matrix metalloproteinase (MMP)-1, -3 and -13 in IL-$1{\beta}$-induced SW1353 chondrosarcoma cells. The chondro-protective effects of CMPB803-C and acetylshikonin were than analyzed in a rat OA model using a single intra-articular injection of MIA (1mg) in the right knee joint. CMPB803-C (200mg/kg) or acetylshikonin (5mg/kg) was orally administered daily for two weeks starting after 1 week of MIA injection. In the histological observation, CMPB803-C and acetylshikonin clearly improved OA lesions being comparable to or better that control group. Our results demonstrated that CMPB803-C and acetylshikonin as active compound of Lithospermum erythrorhizon have a strong chondro-protective effect in OA rats, which likely attributes to its anti-inflammatory activity and inhibition of MMPs production.

• 분석과학
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• 제28권4호
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• pp.260-269
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• 2015

골관절염에 대한 참당귀 추출분말의 치료효과를 검토하고자 흰쥐의 monosodium iodoacetate(MIA)로 유발된 골관절염 부위에서 시료를 채취하여 염증관련 효소 및 염증성 cytokines의 발현에 대하여 참당귀 추출분말의 억제효능을 검토하였다. 고농도의 참당귀 추출분말 (50 μg/mL) 투여에서도 독성이 관찰되지 않았으며, 동일조건하에서 interleukin-1α (IL-1α)로 유발된 nitric oxide (NO)의 생성을 효과적으로 억제하였다. 특히, 관절연골 조직의 inducible nitric oxide synthase (iNOS) 및 cyclooxygenase-2(COX-2)의 발현을 농도 의존적으로 억제하였다. 따라서 참당귀 추출분말은 항염증 효능을 나타내는 농도에서 독성 없이 사용할 수 있으며, iNOS발현을 억제하여 방출되는 신호전달 물질인 NO의 생성을 억제하였다. 또한 참당귀 추출분말의 처리로 염증유발 부위에서 염증성 cytokines으로 알려진 tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) 및 interleukin-6 (IL-6)의 발현이 억제됨을 확인하였다. 참당귀 추출분말의 항 염증효과는 TNF-α, IL-1β 및 IL-6의 혈중농도를 낮추어 염증부위뿐만 아니라 전체적으로 항염증효과를 나타내었다. 본 실험결과, 참당귀 추출분말의 투여는 MIA 또는 IL-1α로 유발되는 골관절염 동물모델에서 염증인자, 관련 효소의 발현 및 관련 신호전달 물질의 생성을 효과적으로 억제하여, 슬관절의 활액 내 glycosaminoglycan (GAG) 및 관절연골의 proteoglycan (PG)의 분해를 방지하여 골관절염의 발생을 억제할 것으로 추정되었다. 한편, 참당귀 추출분말의 주성분인 decursin은 혈중에서 2시간이내에 decursinol로 전환되어 8시간이상 LC-MS/MS로 검출되었다, 따라서 참당귀 추출분말에 의한 염증성 사이토카인 TNF-α, IL-1β 및 IL-6의 억제활성은 항염증활성이 큰 decursinol에 의한 것으로 추정된다.

• 동의생리병리학회지
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• 제31권1호
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• pp.46-51
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• 2017

The aim of this study is to investigate anti-arthritis activity using a KV pharmacopuncture. KV pharmacopuncture was inserted at BL40 for 4 weeks to SD-Rat, where arthritis was induced by monosodium iodoacetate (MIA) at 60 mg/ml. MMP-9, CTX II, LTB4, calcitonin and glycosaminoglycan level in serum were measured by ELISA. The cartilage of patella volume was examined and 3-D high-resolution reconstructions of the cartilage of patella were obtained using a Micro-CT system. Also, The histopathological change of knee was observed by H&E and safranin-O staining. Production of MMP-9, CTX II and LTB4 level in serum was decreased, respectively, in comparison with control. The other way, production of calcitonin and glycosaminoglycan level in serum was increased, respectively, in comparison with control. The cartilage of patella volume increased significantly. In addition, the KV group showed a increase in the cartilage volume and proteoglycan. These results may be used a remedy for new korea medicine to ease the symptoms mentioned above.

• 대한본초학회지
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• 제32권6호
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• pp.63-69
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• 2017

Objectives : The purpose of this study is to investigate the preventive and therapeutic efficacy of osteoarthritis using a Yeonsan-Ogye egg. so, we researched at effects of Yeonsan-Ogye egg extract on MIA-induced Osteoarthritis animal models. Methods : Yeonsan-Ogye egg extract was administered 500 mg/kg/day, 1000 mg/kg/day and 2000 mg/kg/day to SD-Rat for 2 weeks. After that, osteoarthritis was induced with $60mg/m{\ell}$ of monosodium iodoacetate (MIA) and futher administration was continued for 4 weeks. 3D imaging of cartilage patella were obtained using a Micro-CT system and the pathology change of knee was observed by H&E and safranin-O staining. The weight bearing ratio was measured by incapacitance test meter. MMP-2, MMP-9, COMP, CTX II, calcitonin and glycosaminoglycan level in serum were measured using a ELISA. Results : Micro-CT and Histopathological analysis showed the volume of the patella cartilage and the proteoglycan contents were increased in all groups. also weight bearing ratio was decreased in all groups compared with control group. Calcitonin production was increased in and 2000 mg/kg/day group and glycosaminoglycan production was increased in all groups. In addition, MMP-2, MMP-9, COMP and CTX II production were decreased in 1000 and 2000 mg/kg/day groups respectively in comparison with control. Conclusions : The results for Yeonsan-Ogye egg showed prevention and treatment efficacy against arthritis at serum and the cartilage. These results may be used a remedy for new korea medicine to ease the symptoms mentioned above. also, suggest that Yeonsan-Ogye egg can be used preventive and therapeutic material for osteoarthritis.

• 대한한의학회지
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• 제34권3호
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• pp.69-85
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• 2013

Objectives: This study investigated the anti-osteoarthritic effects of Kyejiinsam-tang (hereinafter referred to KIT) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods: Anti-oxidative effects of KIT were measured by scavenging activities of DPPH, reactive oxygen species (ROS) and nitric oxide (NO). Scavenging activities of anti-oxidation in lipopolysaccharide (LPS)-treated RAW 264.7 cells were also measured for inhibitory effects against the production of inflammatory mediators (tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, interleukin-6). Osteoarthritis was induced in rats by injecting MIA in the knee joint. Rats were divided into a total of 4 groups (n=6). The normal group were not treated at all without inducing osteoarthritis whereas the control group were induced for osteoarthritis by MIA and oral medicated physiological saline per day. The positive comparison group was injected with MIA and after 7 days, 2 mg/kg of Indomethacin. The experimental group was injected with MIA and after 7 days was medicated with 34 mg/kg of KIT. Indomethacin and KIT were orally-medicated for each substance a total of 4 weeks, once per day. Weight-bearing on hind legs was measured every week after MIA injection. At the end of the experiment (5 weeks after MIA injection), micro CT (computed tomography)-arthrography and histopathological examinations on the articular structures of knee joint were performed. The effect on inflammatory cytokines and immunological cells in synovial fluid was measured. Volume of cartilage was measured by micro CT-arthrography. Injury to synovial tissue was measured by H & E (hematoxylin and eosin), Safranin-O immunofluorescence. Results: 1. Cytotoxicity against hFCs was insignificant. 2. KIT showed the potent full term for DPPH. 1. NO was significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and ROS was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 2. IL-6 and IL-$1{\beta}$ were significantly reduced by KIT (at 100, $200{\mu}g/m{\ell}$) and TNF-${\alpha}$ was also reduced, but not significantly, by KIT (at $200{\mu}g/m{\ell}$). 1. In hind legs weight-bearing measurement, level of weight increased. 2. Functions of liver and kidney were not affected. 3. IL-$1{\beta}$ was significantly reduced and TNF-${\alpha}$, IL-6 were also reduced but not significantly. 4. PGE2 (prostaglandin E2), LTB4 (leukotriene B4) were significantly reduced in the KIT group. 5. MMP-9 (matrix metalloproteinase-9), TIMP-1 (tissue inhibitor of metalloproteinases-1) and Osteocalcin were significantly reduced in the KIT group. 6. Destruction of cartilage on micro CT arthrography was reduced but had no significant differences. 7. Histopathologically, injury to synovial membrane of the KIT group was decreased and proteoglycan content of KIT group was increased. Conclusions: According to this study, Kyejiinsam-tang has inhibiting effect on the progression of arthritis in MIA-induced osteoarthritis rat. Kyejiinsam-tang has anti-oxidants and anti-inflammation effects, and is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• 한국식품영양과학회지
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• 제45권5호
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• pp.634-641
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• 2016

본 연구에서는 오디추출복합물(mulberry extract complex, MEC)의 퇴행성관절염 증상 완화 및 개선 효과 가능성을 탐색하기 위하여 monosodium iodoacetate(MIA)로 유도한 퇴행성관절염 in vivo 실험모델을 이용하였다. 연골의 주요 구성성분인 glycosaminoglycan(GAG) 및 collagen의 농도를 실험동물의 연골에서 측정한 결과 MIA로 인해 감소하였던 GAG 및 collagen의 농도가 MEC를 경구 투여한 실험군에서 농도 의존적으로 증가하였다. 또한 교원질 합성을 억제하고 분해를 촉진하는 matrix metalloproteinase-2, 9, 13의 농도를 측정한 결과는 MEC의 농도에 따라 감소하는 결과를 보여주었다. 연골 손상 지표인 cartilage oligomeric matrix protein과 C-terminal telopeptide 2의 측정결과에서는 대조군보다 유의성 있는 감소를 나타내어 MEC가 퇴행성관절염의 진행 억제에 도움을 줄 수 있을 것으로 생각된다. 관절염 지수 평가에서도 MEC는 모든 농도에서 대조군보다 유의성 있게 개선되는 결과를 나타내었다. 이상의 실험 결과를 통하여 MEC가 퇴행성관절염에서 나타나는 연골 구성성분의 분해를 억제하고, 여러 중요한 퇴행성관절염 진행 인자를 효과적으로 억제하여 결국 연골파괴 감소와 더불어 통증을 줄여줌으로써 퇴행성관절염에 대한 증상 완화 및 개선 효과가 있을 수 있는 건강기능식품의 원료로 활용될 수 있을 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권2호
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• pp.163-172
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• 2018

PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after $H_2O_2$ treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, $IL-1{\beta}$, $TNF-{\alpha}$, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, $IL-1{\beta}$, p-Erk1/2, $NF-{\kappa}B$, $TNF-{\alpha}$, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating $IL-1{\beta}$, $TNF-{\alpha}$, and subsequent signals, such as p-Erk1/2, $NF-{\kappa}B$, COX-2, PGE2, and MMPs.

• 대한한의학방제학회지
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• 제29권3호
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• pp.127-145
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• 2021

Objectives : The purpose of this study was to evaluate the effects of Daeganghwal-tang on knee cartilage in monosodium iodoacetate(MIA)-induced osteoarthritis rats. Methods : Forty SD rats were randomly divided into five groups(n=8/group): normal group was SD rats group injected with normal saline at left knee joint and administrated orally distilled water, control group was MIA-induced osteoarthritis SD rats group administrated orally distilled water, Indomethacin group was MIA-induced osteoarthritis SD rats group administrated orally indomethacin 2 mg/kg, DGHT(L) group was MIA-induced osteoarthritis SD rats group administrated orally 1280 mg/kg of Daeganghwal-tang, and DGHT(H) group was MIA-induced osteoarthritis SD rats group administrated orally 2560 mg/kg of Daeganghwal-tang. After orally administration of drugs for 4 weeks, gross appearance and histological analysis were used to evaluate the degree of knee cartilage damage. In addition, pro-inflammatory cytokines, bone degrade factor and bone defence factors were analyzed to investigate the anti-inflammatory and cartilage protection effects of Daeganghwal-tang. Also, hematological test, biochemical test, and liver and kidney tissue were analyzed to determine the safety of Daeganghwal-tang. Results : Daeganghwal-tang inhibited the damage of the knee cartilage, and significantly prevented the reduction in cartilage thickness. In addition, the pro-inflammatory cytokines and the bone degrade factor significantly decreased, and the bone defence factors significantly increased. In the safety assessment of Daeganghwal-tang, there were no significant differences among the experimental groups and no abnormal findings were observed. Conclusions : Daeganghwal-tang has anti-inflammatory effect, inhibits cartilage damage, and protects cartilage in MIA-induced osteoarthritis rats.

• 한방재활의학과학회지
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• 제33권3호
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• pp.17-32
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• 2023

Objectives The purpose of this study was to investigate the antioxidant, anti-inflammatory and cartilage regeneration effects of Euiiin-tang water extract (EIIT) in the treatment of monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Methods Animal models were divided into five groups. The normal group didn't do any treatments causing osteoarthritis. The control group was orally administerd distilled water instead of the drug, the positive control group used indomethacin 5 mg/kg, the EIIT 100 group used EIIT 100 mg/kg and the EIIT 200 group used EIIT 200 mg/kg, and seven rats were placed per group. We administered drug to rats for 2 weeks and analyzed oxidative stress-related proteins in joint tissue. Inflammation mediators and inflammatory cytokines induced by the activity of inflammation-related proteins were analyzed. In addition, the expression of anti-inflammatory cytokines and collagen-related factors were analyzed, and H&E staining and Safranin-O staining were performed to see the effect on histopathological changes. Results 1) Oxidative stress-related proteins were significantly reduced. 2) Inflammationrelated proteins, inflammatory mediators and inflammatory cytokines were significantly reduced. 3) Anti-inflammatory cytokines were significantly increased. 4) Collagen proteolysis factors significantly decreased, and collagen degradation inhibitory factor was significantly increased. 5) EIIT administration significantly reduced cartilage degeneration and deformation in H&E staining, and reduced proteoglycan destruction in Safranin-O staining. Conclusions From the above experimental results, it judges that Euiiin-tang has antioxidant, anti-inflammatory, and cartilage regeneration effects on osteoarthritis in rats induced by MIA.