• Journal of Korean Medicine Rehabilitation
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• v.21 no.4
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• pp.49-65
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• 2011

Objectives: This study was performed to investigate the effects of Gagamsosokmyeong-tang(Jiajianxiaoxuming-tang) on the monosodium iodoacetate(MIA) induced early state osteoarthritis in rats. Methods: Osteoarthritis was induced by injection of MIA(0.25 mg) into knee joints of rats. Osteoarthritis rats were divided into control(n=8) and treated=8 group respectively, Control group was taken distilled water and treated group was taken extracts of Gagamsosokmyeong-tang(Jiajianxiaoxuming-tang) by orally for 20 days. Body weight was measured at 0, 5, 10, 15, 20 days after MIA injection. At the end of experiment, gross and histopathological examination on the articular cartilages of the knee joints were performed. Proteoglycan(PG) content of articular cartilages were analysed by safranine O staining method. The content of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$ in synovial fluids were analysed by enzyme-inked inmunosorbent assay(ELISA) method. And also cycloxygenase-2(COX-2), matrix metalloproteinase 3(MMP-3), inducible nitric oxide synthase(iNOS), calpain immunochistochemical examination on the knee joints were performed. Results: PG content in articular cartilages of the treated group was significantly increased compared with control group. Histopathological osteoarthritic score of the treated group was significantly decreased compared with control group. $TNF-{\alpha}$ content in synovial fluids, expression of iNOS and calpain in synovial membrane of the treated group were significantly decreased compared with control group. But body weight, $1L-1{\beta}$ content in synovial fluids, expression of iNOS and MMP-3 of the treated group were not significantly changed compared with control group. Conclusions: On the basis of these results, we conclude that Gagamsosokmyeong-tang(Jiajianxiaoxuming-tang) has anti-arthritic effects on the MIA induced early stage osteoarthritis in rats.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.37-50
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• 2015

Objectives The purpose of this study was to know the effects of Danggwisayeok-tang (Dangguisinitang) extract (DGSYT) on monosodium iodoacetate (MIA)-induced rat osteoarthritis. Methods For this purpose, rats were divided into 5 groups. Normal group was not injected with MIA and orally administered any medication. Control group was injected with MIA and not orally administered any medication. DGSYT100 group was injected with MIA and orally administered 100 mg/kg of DGSYT. DGSYT300 group was injected with MIA and orally administered 300 mg/kg of DGSYT. JoinsT group was injected with MIA and orally administered 20 mg/kg of Joins tablet. DGSYT100 and DGSYT300 groups were orally administered DGSYT during a week before and 3 weeks after based on the day MIA injected. The changes of hepatotoxicity, nephrotoxicity, relative hind paw weight distribution, cytokine in serum, cytokine messenger ribonucleic acid (mRNA) in joint tissue and histopathological observation (Hematoxylin & Eosin and Safranin-O staining) were measured. Results Alanine aminotransferase (ALT) levels of DGSYT100, DGSYT300 and JoinsT groups were increased significantly, but these results were within normal range. Aspartate aminotransferase (AST) and creatinine levels of all groups were not changed significantly. In the change of relative hind paw weight distribution, DGSYT300 and JoinsT groups were decreased significantly 14 and 21 days after MIA injected. Interleukin-$1{\beta}$ (IL-$1{\beta}$) and Interleukin-6 (IL-6), Leukotriene $B_4$ and Osteocalcin levels of DGSYT300 and JoinsT groups were decreased significantly. In measurement of IL-$1{\beta}$ and nitric oxide synthase-II mRNA relative quantitative of control, DGSYT100, DGSYT300 and JoinsT groups were decreased significantly. In measurement of TNF-${\alpha}$, IL-6 and Cyclooxygenase-2 mRNA relative quantitative of control, DGSYT300 and JoinsT groups was decreased significantly. In histopathological observation of knee, synovial tissue, cartilage and proteoglycan of DGSYT100, DGSYT300 and JoinsT were well preserved compared with control group. Conclusions According to the results, DGSYT has anti-inflammation and pain relief effects. So it should be suppressed progression of arthritis in MIA-induced osteoarthritis rat.

• Journal of Korean Medicine Rehabilitation
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• v.23 no.4
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• pp.23-37
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• 2013

Objectives This study was performed to investigate the effects of Saengkanggamchotang (SKT) on the monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of MIA (50 ul, 60 mg/ml) into knee joints of rats. Rats are divided into a total of 4 groups (normal, control, positive comparison group, SKT treated group, each n=6). Normal group are not treated at all without inducing osteoarthritis whereas control group were induced for osteoarthritis by MIA and oral medicated with 20 ml of distilled water per day. Positive comparison group was injected with MIA and after 7 days, that was taken indomethacin (30 mg/kg/mouse). SKT treated group was injected with MIA and after 7 days that was taken SKT (30 mg/kg/mouse). Positive comparison group and SKT treated group were oral medicated for each substance a total of 4 weeks with one time per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the functions of liver and kidney, Prostaglandin E2, inflammatory cytokine (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), osteocalcin, TIMP-1, MMP-9 within serum. Knee joint structures were observed by H&E, safranin-O staining method, and amount of cartilage were measured by ${\mu}CT$-arthrography. Results 1) Hind paw weight bearing ability was significantly improved. 2) Functions of liver and kidney were not affected. 3) Prostaglandin E2, osteocalcin, TIMP-1, MMP-9 in serum were significantly decreased. 4) Inflammatory cytokine IL-$1{\beta}$ was significantly decreased, and IL-6, TNF-${\alpha}$ were decreased but had not significant. 5) In terms of histopathology, significantly reduced subsidence of cartilage and bone in H&E staining. And in Safranin O staining, proteoglycan content in synovial membrane was significantly increased compared with control group. 6) Destruction of cartilage on ${\mu}CT$-arthrography was significantly reduced. Conclusions Based on all results mentioned above, Saengkanggamchotang (SKT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments.

• Journal of Korean Medicine Rehabilitation
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• v.28 no.1
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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.

• Journal of Korean Medicine Rehabilitation
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• v.20 no.1
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• pp.61-77
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• 2010

Objectives : The purpose of this study was to investigate the effects of Bee Venom (BV) and Cervi Cornu Parvum pharmacoacupuncture (CC) in monosodium iodide induced arthritis rats. Methods : The subjects were divided into 5 groups ; Normal, Control (no treatment after MIA), BV (Bee Venom pharmacoacupuncture $100{\mu}{\ell}$ daily at Dokbi (ST35) after inducing MIA), CC (Cervi Cornu Parvum pharmacoacupuncture $100{\mu}{\ell}$ dailyat Dokbi (ST35) after inducing MIA) and BV+CC (Bee Venom pharmacoacupuncture and Cervi Cornu Parvum pharmacoacupuncture $100{\mu}{\ell}$daily at Dokbi (ST35) after inducing MIA). After each operation, the present author observed the motor behavior recovery, hematological (Prostaglandin E2, AST, ALT), histological and immunological changes. Rats were tested at the 7th, 14th and 21st day. Results : Results are as follows. 1. All the experimental groups were improved compared with control group in plantar test. 2. All the experimental groups were improved compared with control group in touch test for sensory evaluator. 3. All the experimental groups were significantly decreased compared with control group in prostaglandin E2. 4. In histological observations, knee joint in all the experimental groups were improved compared with control group. 5. In immunological observations, all the experimental groups were significantly decreased compared with control group in COX-1, 2. Conclusions : It can be suggested that Bee venom and Cervi Cornu Parvum pharmacoacupuncture may improve motor behavior, hematological, histological and immunological findings in MIA-induced osetoarthritis rats. Especially, combination of these two treatments will be somewhat better in osteoarthritis recovery and motor function improvement.

• IMMUNE NETWORK
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• v.14 no.1
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• pp.45-53
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• 2014

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-$1{\beta}$, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-$1{\beta}$-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

• The Korea Journal of Herbology
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• v.33 no.3
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• pp.45-53
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• 2018

Objectives : In cases of osteoarthritis, the hypofunction of the cartilage and joint leads to a limited range of joint motion, swelling, and pain, which is generally treated using pharmaceutical drugs (e.g., anti-inflammatory agents, cartilage protectants, and nonsteroidal anti-inflammatory drugs) or replacement arthroplasty. However, long-term drug treatment is associated with adverse effects on the gastrointestinal systems. The present study aimed to evaluate the ability of Giheolsotong-hwan to treat of osteoarthritis symptoms in the MIA-induced rat model based on histological analysis, and factors that are associated with inflammation and bone mineral metabolism. Methods : Giheolsotong-hwan was administered orally at doses of 200 mg/kg/day or 400 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}{\ell}$ of 0.9% saline) into the intra-articular space of the rats' right knee. The rats subsequently received the same doses of oral Giheolsotong-hwan for another 4 weeks. We evaluated the treatment effects based on serum biomarkers and histopathological analysis of the knee joints. Results : Compared to those in control rats, the Giheolsotong-hwan treatments significantly decreased the serum concentration of inflammation factors (i.e., $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $PGE_2$, and $LTB_4$), and bone degrade factors (i.e., MMP-9, CTX-II, and COMP). In addition, the Giheolsotong-hwan treatments significantly increased the concentration of glycosaminoglycans of bone defence factors, but no chage the TIMP-1. Furthermore, the Giheolsotong-hwan treatments effectively preserved the knee cartilage and proteoglycan. Conclusion : The results indicate that Giheolsotong-hwan treated osteoarthritis symptoms. Thus, Giheolsotong-hwan may be a novel oriental therapeutic option for the management of osteoarthritis.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.2
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• pp.65-81
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• 2014

Objectives This study was carried out to find out the anti-osteoarthritic effects of Mahwangbujaseshin- tang (Mahuangfuzixixintang ) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injecting MIA ($50{\mu}l$) into the knee joint of rats. Rats were divided into a 3 groups (n=7). The injection did not fit the normal group. A week later, after the injection of MIA, while control group took normal saline 2 ml, the extract of Mahwangbujaseshin-tang (Mahuangfuzixixintang ) (MBST) (200 mg/kg) was injected to treated group. After that, we examined hind paw weight bearing ability, functions of liver and kidney, serum TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, TIMP-1, MMP-9 and hematology. Volume of cartilage was measured by micro CT arthrography. Injury of synovial tissue was measured by H & E, Safranin-O immunofluorescence. Results 1) DPPH and ABTS free radical scavenging activity of MBST was increased according to concentration of MBST and total phenolic contents were in high level. 2) In RAW 264.7 cells, ROS production was significantly decreased in MBST (at 10, $100{\mu}g/ml$) and NO was also decreased but meaningless in MBST (at $100{\mu}g/ml$). 3) In RAW 264.7 cells, IL-6 production was significantly decreased in MBST (at $100{\mu}g/ml$) and TNF-$\alpha$ and IL-$1{\beta}$ production were also decreased but meaningless in MBST (at $100{\mu}g/ml$). 4) In hind legs weight-bearing measurement, level of weight-bearing was increased. 5) Functions of liver and kidney were not affected. 6) TNF-$\alpha$, IL-$1{\beta}$, IL-6, $PGE_2$, $LTB_4$, MMP-9 and TIMP-1 production were significantly decreased. 7) In hematology, the levels of neutrophils, monocytes were significantly decreased and the levels of white blood cells, lymphocytes were also decreased but meaningless. 8) In micro CT-arthrography, cartilage volume was significantly increased. 9) Histopathologically, injury on cartilage and synovial membrane of MBST group was decreased. Conclusions Based on all results mentioned above, Mahwangbujaseshin-tang (Mahuangfuzixixintang) is believed to be meaningful for suppressing the progress of osteoarthritis. And it is related to inhibiting the activity of inflammatory cytokine and injury of volume in cartilage.

• Journal of Korean Medicine Rehabilitation
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• v.30 no.2
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• pp.1-18
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• 2020

Objectives This study intended to evaluate antioxidative, anti-inflammatory effects of Jibaekjihwang-tang on monosodium iodoacetate (MIA)-induced osteoarthritic rat model and investigate the potential mechanism. Methods Jibaekjihwang-tang (100 or 200 mg/kg body weight) was orally administered once daily for 2 weeks days from day 7 after intra-articular MIA injection. And blood analysis, the histologic examinations were performed. Moreover, protein expressions related to anti-oxidant and cartilage degradation and anti-inflammatory cytokines were measured by western blot analysis in cartilaginous tissue. Results Jibaekjihwang-tang reduced serum inflammatory cytokines such as tumor necosis factors-α and interleukin-6. Furthermore, the increase of anti-oxidant enzymes reversed the oxidative stress caused by MIA. Meanwhile, Jibaekjihwang-tang suppressed MIA-induced inflammation and cartilage degradation in cartilaginous tissue. Conclusions Jibaekjihwang-tang alleviated MIA-induced inflammation. Jibaekjihwang-tang was associated with a protective effect on cartilage and by reducing inflammation and cartilage degradation. These findings provide new approaches for understanding osteoarthritis therapy.

• Korean Journal of Pharmacognosy
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• v.51 no.2
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• pp.122-130
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• 2020

To investigate the anti-inflammatory effect on Degenerative Osteoarthritis, Male sprague-Dawley rats were randomized and classified into three different concentration groups. We measured weekly weight change, dietary intake, drinking water intake, blood analysis like TNF-α (tumor necrosis factor-α), IL-6 (interleukin 6), TIMP-1 (tissue inhibitor of metalloprotease-1), MMP-2 (matrix metalloprotease-2), MMP-9 (matrix metalloprotease-9) and micro CT analysis. The results suggest that the treatment with herbal complex HP-04 improved the Monosodium iodoacetate (MIA) induced degenerative osteoarthritis and it could be applicable for the improvement of arthritic symptoms as a new therapeutic agent.