• Korean Journal of Acupuncture
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• v.33 no.4
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• pp.204-212
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• 2016

Objectives : The aim of the study is to investigate the effects of moxibustion on the pain behavior and expression of TRPM8 in the dorsal root ganglion(DRG) in the rat model of ambient cold(AC) exposed osteoarthritis(OA). Methods : OA was induced by the injection of $50{\mu}l$ of 2% monosodium iodoacetate(MIA) into the knee joint cavity. To examine the level of pain, weight bearing forces(WBFs) of affected limb was measured. For the AC exposure, the animals were housed in 6 h/day at $4^{\circ}C$ for 14 days after MIA injection. Moxibustion treatment was performed at EX-LE4 and EX-LE5 with 5 cons(1, 7 or 10 mg) per day for 13 days from 5 days after MIA injection. The expressions of TRPM8 in DRG were measured by western blotting analysis. Results : The WBFs of MIA-AC group were decreased significantly compared to MIA group at 2, 3, 6, 7, 8 and 9 days after arthritis induction. After the first 6 h-AC exposure, expressions of TRPM8 in MIA-AC group were increased significantly compared to those of naive group. After moxibustion treatment, only the WBFs of 7 mg treated group were restored significantly. Moreover, the over-expressions of TRPM8 were attenuated by the moxibustion treatment in AC exposed rats. Conclusions : The data suggest that AC can increase arthritic knee pain via up-regulated TRPM8 and moxibustion treatment improve the arthritic pain via modulation of TRPM8 expression in DRG in the rat model of AC exposed MIA induced arthritis.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.2
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• pp.51-64
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• 2015

Objectives This study was carried out to investigate the effects of Gyejigabuja-tang extracts on the Monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of MIA into knee joint cavity of rats. Rats are divided into 4 groups (normal, control, positive comparison group, GBT group, each n=5). Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and oral medicated with distilled water. Positive comparison group was injected with MIA and taken Joins tablet 25 mg/kg. GBT group was injected with MIA and taken Gyejigabuja-tang extracts 300 mg/kg. Positive comparison group and GBT group were oral medicated for each substance once a day for 4 weeks. ALT, AST and creatinine were evaluated for hepatotoxicity and nephrotoxicity. Hind paw weight bearing ability was examined and inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), $PGE_2$, $LTB_4$, osteocalcin and deoxypyridinoline (DPD) within serum were analysed. Knee joint structures were observed by Hematoxylin & Eosin (H&E), Safranin-O staining method. Results 1. Function of liver and kidney was not affected. 2. Hind paw weight bearing ability was significantly improved. 3. IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ in experimental group were significantly decreased compared with control group. 4. $PGE_2$, $LTB_4$, Osteocalcin and DPD in experimental group were decreased compared with control group. 5. In histopathologic observation, injury on synovial membrane and cartilage of experimental group was lesser than control group (H&E, Safranin-O staining). Conclusions Based on these results, it can be suggested that Gyejigabuja-tang has anti-inflammation effects on the MIA-induced osteoarthritis in rats.

• Korean Journal of Plant Resources
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• v.33 no.6
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• pp.638-644
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• 2020

Lilium lancifolium (LL) is widely cultivated in East Asia and used to attenuate airway diseases. Our current study aimed to investigate the therapeutic effect of LL on pain level and inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). We first examined the effect of LL on inflammatory cytokines and inflammatory mediators in IL-1β-treated HTB-94 cells. The LL extract was found to significantly inhibit the levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), and prostaglandin-E2 (PGE-2) in Interleukin-1 β (IL-1β)-stimulated HTB-94 cells in a dose-dependent manner. Moreover, chronic oral administration of LL effectively restored the weight-bearing distribution in the rat model of MIA-induced OA. In addition, administration of LL inhibited inflammatory cytokines and inflammatory mediators, such as C-reactive protein (CRP), IL-6, leukotriene B4 (LTB-4), PGE-2, and matrix metalloproteinase-9 (MMP-9). Our findings collectively suggested LL as one of the potential therapeutic agents for OA, owing to its properties of reducing pain and inflammatory responses.

• Journal of Korean Medicine Rehabilitation
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• v.26 no.3
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• pp.1-15
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• 2016

Objectives This study was designed to evaluate the anti-inflammatory effects of Seungseup-tang (SST) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injection of MIA ($50{\mu}l$ with 80 mg/ml) into knee joint cavity of rats. Rats were divided into 4 groups (normal group, control group, indomethacin treated group, SST treated group, each n=6). Normal group was not injected with MIA and taken normal diet. Control group was injected with MIA and taken with distilled water. Indomethacin treated group was injected with MIA and taken indomethacin 5 mg/kg by oral administration. SST treated group was injected with MIA and taken SST 200 mg/kg by oral administration. We examined the weight-bearing ability of hind paw, biomarkers related to oxidative stress in serum, inflammatory proteins and inflammatory mediators and cytokines. Moreover, histopathological examination of knee joint structure was also performed by Hematoxylin & Eosin (H&E), Safranin-O staining method. Results In the present study, SST treated group showed a similar inhibitory effects alike indomethacin treated group, in most of the studied parameters of inflammation. The increased oxidative stress biomarker such as reactive oxygen species (ROS) and peroxy nitrite ($ONOO^-$) in the serum were reduced with SST. Especially, the level of $ONOO^-$ compared with control group significantly suppressed. Also, the expression of inflammatory mediators and cytokines induced by nuclear factor-kappa B (NF-${\kappa}B$) activation was modulated through inhibition of IkBa phosphorlation. In addition, histological analysis revealed that cartilage damage by MIA repaired markedly in SST treated group. Conclusions According to the results, Seungseup-tang may be effective for preventing the progression of osteoarthritis.

• The Journal of Korean Medicine
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• v.40 no.3
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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.

• The Journal of Internal Korean Medicine
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• v.43 no.6
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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.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.830-838
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• 2020

The present study aimed to evaluate the effect of radiation mutant Perilla frutescens var. crispa on bone metabolism and the inflammatory response in a monosodium iodoacetateinduced rat model of osteoarthritis. radiation mutant Perilla frutescens var. crispa was administered orally at doses of 25, 50 or 100 mg/kg/day for 2 weeks before direct injection of monosodium iodoacetate (3 mg/50 μl of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral radiation mutant Perilla frutescens var. crispa for another 4 weeks. It was evaluated that the treatment effects based on serum biomarkers, and morphological and histopathological analysis of the knee joints. Compared with those in control rats, the radiation mutant Perilla frutescens var. crispa treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., COX-2, LTB4, MMP-3, and COMP), and the amount of fibrous tissue. Otherwise, it was significantly increased the concentration of TIMP-1 and calcitonin. In addition, the radiation mutant Perilla frutescens var. crispa treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that radiation mutant Perilla frutescens var. crispa prevented and alleviated osteoarthritis symptoms. Thus, radiation mutant Perilla frutescens var. crispa can be used in food and drug material for the management of osteoarthritis.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.361-361
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• 2018

• Analytical Science and Technology
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• v.28 no.6
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• pp.361-369
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• 2015

The precise mechanism underlying the therapeutic efficacy of an extraction powder of Angelica gigas (AGE) for the treatment of degenerative osteoarthritis was investigated in primary cultured rabbit chondrocytes and in a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. The treatment with AGE (50 μg/mL) effectively inhibited NF-B activation. The anti-inflammatory mechanism was clarified by gelatin zymography and western blotting measurements of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. The AGE (50 μg/mL) treatment significantly reduced MMP-9 activity. The constituents of AGE— decursinol, decursin, and decursinol angelate—were determined by LC-MS/MS after a 24 hr treatment of rabbit chondrocytes. The contents of the major products, decursin and decursinol angelate, were 3.62±0.47 and 2.14 ±0.36 μg/mg protein, respectively in AGE-treated (50 μg/mL) rabbit chondrocytes. An in vivo animal study on rats fed a diet containing 25, 50, and 100 mg/kg AGE for 3 weeks revealed a significant inhibition of the MMPs in the MIA-induced rat articular cartilage. The genetic expression of arthritic factors in the articular cartilage was examined by RT-PCR of collagen Type I, collagen Type II, aggrecan, and MMP (MMP3, MMP-9, MMP13). Specifically, AGE up-regulated the expression of collagen Type I, collagen Type II, and aggrecan and inhibited MMP levels at all tested concentrations. Collectively, AGE showed a strong specific site of action on MMP regulation and protected against the degeneration of articular cartilage via cellular regulation of MMP expression both in vitro and in vivo.

• 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.