• 대한한의학회지
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• 제40권3호
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• pp.35-58
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• 2019

Objectives: The aim of this study was to investigate the anti-inflammatory effects of Curcuma longa rhizoma extract in an experimental rat model of osteoarthritis. Methods: Osteoarthritis was induced in rats by injecting monosodium iodoacetate (MIA) into the knee joint cavity of rats. The rats were divided into 5 groups (Normal, Control, positive comparison, low (CL) and high (CH) concentration groups). Rats in the low concentration (CL) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 50mg/kg body weight. Rats in the high concentration (CH) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 100mg/kg body weight. Hind paw weight distribution and ROS levels were measured. At the end of all treatments, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were analyzed. In addition, inflammatory protein levels were evaluated by western blot analysis. Results: In this study, hind paw weight distribution significantly improved in the CL and CH groups, while. Reactive oxygen species (ROS) production significantly decreased in both. The levels of ALT, AST, BUN, and creatinine did not significantly change in either group. The production of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), $p47^{phox}$, and Ras-related C3 botulinum toxin substrate 1 (RAC1) decreased in both. Catalase, heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) significantly increased in the CL and CH groups, respectively. Nuclear factor erythroid 2 (Nrf2) increased, but there were no significant differences between the experimental and control groups. Inflammatory cytokines, including nuclear factor-kappa Bp65 (NF-${\kappa}Bp65$), interleukin-1beta (IL-$1{\beta}$), and tumor necrosis factor-alpha (TNF-${\alpha}$), decreased significantly in both the CL and CH groups. Conclusions: Our results showed that Curcuma longa rhizoma extract has anti-inflammatory effects. Anti-inflammatory activity is regulated by the inhibition of inflammatory cytokines and mediators, such as NF-${\kappa}B$, therefore, it suppresses cartilage damage as well.

• 한국식품영양학회지
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• 제32권6호
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• pp.678-686
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• 2019

The purpose of this study was to examine the physiochemical characteristics of hot water extract of Caragana sinica roots and verified its protective effect on MIA-induced osteoarthritis in rats. The contents of total polyphenol and total flavonoid used in this experiment were 0.40 mg/g and 0.22 mg/g respectively. We found that the weight of all experiment groups which ingested Caragana sinica extract for three weeks evenly increased in rats with MIA-induced osteoarthritis without toxicity in the liver or kidney. In the histopathological test through the Mankin score, the extent of damage of knee joint tissue in the experiment groups to which Caragana sinica extract was administered in 5 mL/kg or 10 mL/kg was significantly lower than that of the negative control groups statistically(p<0.05). As for the grade of osteoarthritis, the extent of tissue damage of the experiment groups to which Caragana sinica extract was administered in 5 mL/kg or 10 mL/kg was lower than that of the negative control groups as well.

• 한방재활의학과학회지
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• 제28권1호
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• pp.19-31
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• 2018

Objectives The object of this study was to investigate the antioxidative and antiinflammatory effects of Jinmu-tang extract (JMT) on the Monosodium iodoacetate (MIA)-induced rat osteoarthritis. Methods To investigate the antioxidant capacities of JMT, we measured the total polyphenol and flavonoid, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-Azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. To evaluate the antioxidative and antiinflammatory effects of JMT, the rats were divided into 5 groups (n=8). Normal group was not induced by MIA and treated at all (N), control group was induced by MIA and not treated at all (Con), positive control group was induced by MIA and orally administered indomethacin 5 mg/kg (Indo) and experimental groups were induced by MIA and orally administered JMT 100 mg/kg (JMT100) and JMT 200 mg/kg (JMT200) for 4 weeks. The changes of anti-type II collagen antibody in serum, heme oxygenase-1 (HO-1), phosphorylated inhibitor of ${\kappa}B{\alpha}$ ($p-I{\kappa}B{\alpha}$), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha ($TNF-{\alpha}$) in knee joint tissue and histopathological observation (Hematoxylin & Eosin and Safranin-O stain) were measured. Results Total polyphenol and flavonoid levels of JMT were $26.90{\pm}0.33mg/g$ and $6.02{\pm}0.34mg/g$. $IC_{50}$ of L-ascorbic acid and JMT of DPPH radical scavenging activity were $1.35{\pm}0.07{\mu}g/ml$ and $52.95{\pm}0.97{\mu}g/ml$. $IC_{50}$ of L-ascorbic acid and JMT of ABTS radical scavenging activity were $3.18{\pm}0.02{\mu}g/ml$ and $91.49{\pm}1.74{\mu}g/ml$. In serum, the anti-type II collagen antibody levels of JMT100 and JMT200 groups were decreased significantly. In knee joint tissue, the HO-1 level of JMT200 was increased significantly. The $p-I{\kappa}B{\alpha}$ and $TNF-{\alpha}$ levels of JMT200 were decreased significantly. The COX-2 and iNOS levels of JMT groups were decreased significantly. In histopathological observation, in comparison with Con, synovial tissue, cartilage and proteoglycan of JMT100 and JMT200 were well preserved. Conclusions According to the results, It is considered that JMT has antioxidant and antiinflammatory effects for MIA-induced rat osteoarthritis, so it could be applied to osteoarthritis treatment.

• 동의생리병리학회지
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• 제21권5호
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• pp.1194-1199
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• 2007

Osteoarthritis(OA) is a degenerative joint disease characterized by fibrillation and erosion in cartilage tissue, chondrocyte proliferation and osteophyte formation at the joint margins, and sclerotis of subchondral bone. We investigated the effects of Acyranthes Radix administration and Cervi Cornu Parvum aqua-acupuncture in monosodium iodoacetate(MIA) induced experimental osteoarthritis model. Sprague-Dawley 60 rats of 7-8 weeks, weight $240{\pm}10\;g$ were divided into two groups including the sham operation group(15 rats) and ostoarthritis group(45 rats). Histopathological examination, Mankin's score, and the measurement of inflammation factor were performed. Histological findings that are similar to those observed in human osteoarthritis, such as disorganization of chondrocytes, erosion and fibrillation of cartilage surface, and subchondral bone exposure were observed in a MIA-induced osteoarthritis model. Saflanin-O fast green staining revealed that marked diffuse reduction of proteoglycans treated with MIA. The Mankin's score were closely correlated to the grade of histological findings. The level of prostaglandin E2 and C-reactive protein were decreased experimental groups. We conclude that Acyranthes Radix administration and Cervi Cornu Parvum aqua-acupuncture, and combination treatment exerts a beneficial influence on the cartilage lesion in osteoarthritis rat.

• 대한한방내과학회지
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• 제43권6호
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• pp.1089-1104
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• 2022

Objective: The aim of this study was to identify the efficacy and underlying mechanism of cloves as an osteoarthritis (OA) treatment in a monosodium iodoacetate (MIA)-induced rat OA model. Osteoarthritis (OA) is nowadays one of the most prevalent degenerative joint diseases. Methods: Sprague-Dawley rats treated with MIA (50 μL; 80 mg/mL) were used as in vivo OA models. Cloves (100 and 200 mg/kg b.w.) were administered orally once daily for 2 weeks from 7 days after MIA injection. Changes in hindpaw weight distribution (HWD) were measured as a joint discomfort index. Activation markers related to inflammatory responses and cartilage degeneration in the right knee joints were evaluated by serum analysis and western blotting. Results: HWD decreased in the MIA control group but showed a dose-dependent elevation after clove treatment. Clove treatment inhibited inflammatory factors by PI3K/Akt/NF-κB signaling pathways, while also activating antioxidant factors through Sirt1/AMPK signaling pathways. Clove treatment also suppressed matrix metalloproteinase (MMP) overexpression and significantly increased the levels of tissue inhibitors of metalloproteinases (TIMPs). Conclusions: Treatment with cloves effectively reversed MIA-induced effects. Therefore, clove treatment could have the potential to protect against or treat OA.

• 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.

• 대한본초학회지
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• 제33권5호
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• pp.53-66
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• 2018

Objectives : This study was designed to compare the effects of acanthopanax stem bark (ASB) and acanthopanax root bark (ARB) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The antioxidant activities were evaluated through radical scavenging assays using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Also, we examined total poly phenol and flavonoids contents. Osteoarthritis was caused by injection MIA($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. Rats were divided by 4 groups (normal group, control group, ASB treated group, ARB treated group, each n=6). The changes in the levels of reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, the anti-oxidant, inflammatory protein levels were investigated western blot analysis. Knee joint tissue, histopathological observation hematoxylin & eosin staining and safranin-O staining were measured. Results : In the present study, ARB treated group showed superior inhibitory effects on the inflammatory parameters than the ASB treated group. ARB aqueous extract was effective in antioxidant measurements. The administration of ARB showed a significant reduction of changes in relative hind paw weight distribution. Morever, it decreased ROS, ALT and AST levels in serum, compared with those of the control rats. The ARB administration inhibited the biomarkers of inflammatory in tissues. Conclusions : ASB aqueous extract and ARB aqueous extract have a great effect on osteoarthritis, and ARB aqueous extract has excellent effect on osteoarthritis through antioxidant and anti-inflammation.

• 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.

• 동의생리병리학회지
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• 제25권1호
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• pp.84-91
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• 2011

This study was to investigate the effects of Gyeonbi-Tang Treatment on the monosodium iodoacetate(MIA)-induced mild osteoarthritis in rats. Arthritis was induced by injection of MIA(0.25 mg) into knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water and treated group was taken extracts of Gyeonbi-Tang by orally for 20days. Body weights were measured at 0, 5, 10, 15, 20 days after MIA injection. At the end of experiment(20day after MIA injection), gross and histopathological examination on the articular structures of knee joints were performed. Proteoglycan(PG) contents in articular cartilages were analysed. And also, tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) and interleukin-1${\beta}$(IL-1${\beta}$) contents in synovial fluids were measured by ELISA method. Body weights of the treated group were significantly increased compared with control group at 15, 20 days after injection. Grossly, the severity of osteoarthritis in the treated group were alleviated compared with control group. PG contents in articular cartilages of the treated group were increased compared with control group. Histopathologically, osteoarthritic scores of the treated group was decreased compared with the control group. TNF-${\alpha}$ contents in synovial fluids of the treated group were significantly decreased compared with control group. On the basis of these results, we concluded that Gyeonbi-Tang Treatment has anti-arthritic effects on the monosodium iodoacetate-induced mild osteoarthritis in rats. And it's effects were related with reduced secretion of TNF-${\alpha}$ from synovial membranes.

• 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.