• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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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.

• Korean Journal of Medicinal Crop Science
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• v.21 no.6
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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.

• Analytical Science and Technology
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• v.28 no.4
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• pp.260-269
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• 2015

The protective effects of extract powder of Angelica gigas on the degeneration of the articular cartilage in rats was investigated with monosodium iodoacetate (MIA)-induced osteoarthritis, The treatment of high concentration (50 μg/mL) of Angelica gigas effectively inhibited nitric oxide (NO) production induced by interleukin-1α (IL-1α) without any cytotoxicity. Specifically, mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were dose dependently reduced by extract powder of Angelica gigas. Importantly, mRNA expression in articular cartilage of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were clearly reduced. The inflammatory cytokines in blood were also reduced as well. These results suggested that the protective effects on the degeneration of the articular cartilage was derived from the inhibitory effects of mRNA and protein expression of tested inflammatory cytokines which is linked to prevent the degradation of proteoglycan (PG), the main matrix content in articular cartilage. Meanwhile, the 2 hrs incubation of decursin, a major compound of extract powder in rat whole blood rapidely converted decursin into decursinol which shows string anti-inflammatory activity. The coverted decursinol was detected after 8 hrs in whole blood by LC-MS/MS. Conclusively, the inhibitory effects of inflammatory cytokines production in osteoarthritis may be derived from the production of decursinol, which performs against inflammatroy cytokines like TNF-α, IL-1β, and IL-6.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.1
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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.

• The Korea Journal of Herbology
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• v.32 no.6
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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.

• The Journal of Korean Medicine
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• v.34 no.3
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.634-641
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• 2016

The objective of this research was to investigate the in vivo effects of treatment with mulberry extract complex (MEC) on cartilage degeneration and pain severity in an experimental model of rat degenerative arthritis. Monosodium iodoacetate ($2mg/50{\mu}L$) was injected into right knee joints of rats, followed by administration of MEC for 8 weeks at 400 mg/kg or 800 mg/kg of body weight. The experimental data show that treatment with MEC inhibited degradation of glycosaminoglycan and collagen in cartilage. On the other hand, concentrations of cartilage oligomeric matrix protein, C-terminal telopeptide-2, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 in serum decreased in comparison with the control. The MEC at all dose levels could inhibit formation of xylene-induced ear edema. In this study, MEC demonstrated significant anti-arthritis activity, which is required for improvement of degenerative arthritis. Based on these results, MEC may be employed for the development of new health foods to ease symptoms of degenerative arthritis.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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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.

• Herbal Formula Science
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• v.29 no.3
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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.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.3
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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.