• The Journal of Internal Korean Medicine
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• v.41 no.1
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• pp.1-13
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• 2020

Objectives: Osteoarthritis (OA) is a chronic and degenerative joint disease characterized by progressive degeneration of articular cartilage. Inflammation is a recognized and important factor of OA progression. The present study was designed to investigate the protective effect of Corni Fructus water extract (CFW) on a monosodium iodoacetate (MIA)-induced rat model of OA. Methods: Osteoarthritis was induced by injection of MIA (50 µL; 80 mg/mL) into the knee joint cavity of rats. After an adaptation period for seven days, the rats were divided into 4 groups (n=8/group): normal, control, indomethacin-treated (5 mg/kg), and CFW-treated (200 mg/kg) groups. The rats were treated orally for 14 days. Pain was evaluated by determining hind paw weight distribution. For biochemical analyses, we measured the changes in reactive oxygen species (ROS) and peroxynitrite (ONOO^-) in the knee joint. The presence of anti-oxidant proteins and inflammatory proteins was determined by western blotting. Results: The administration of CFW significantly improved the hind paw weight distribution. The ROS and ONOO^- levels of knee joint were significantly decreased in the CFW group. CFW inhibited the production of inflammatory mediators, such as COX-2, and inflammatory cytokines, including IL-6 and IL-1β, via the NF-κB signaling pathway. The expression of anti-oxidant enzymes, such as catalase and GPx-1/2 also increased significantly. Conclusions: The findings indicate that CFW has a therapeutic and protective effect on OA by suppression of inflammation. Therefore, CFW could represent a potential and effective candidate for OA treatment.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.4
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• pp.1-14
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• 2023

Objectives The anti-inflammatory and anti-arthritic effects of Youngseonjeatonguem (靈仙除痛飮, YSJTU) was evaluated in a cellular model using RAW264.7 macrophages, which are involved in osteoarthritis (OA), and an animal model using Sprague-Dawley (SD) rats, and a possible mechanism of anti-arthritic actions of YSJTU was presented. Methods RAW264.7 macrophages were activated by lipopolysaccharide (LPS). The production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-𝛼, interleukin [IL]-1𝛽, and IL-6) and inflammatory mediators (nitric oxide [NO] and prostaglandin E2 [PGE2]) was determined by ELISA and Griess assay, respectively. Western blot was performed to determine inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. OA was induced by intra-articular injection of monosodium iodoacetate (MIA) into the right knee joint of SD rats. Results In RAW264.7 macrophages, YSJTU reduced LPS-induced production of TNF-𝛼, IL-1𝛽, and IL-6. In addition, YSJTU inhibited LPS-induced production of NO and PGE2 by suppressing iNOS and COX-2 expression. In SD rats, YSJTU improved MIA-induced OA by reducing swelling, skin heat, and cartilage degradation. In addition, YSJTU reduced serum levels of TNF-𝛼, IL-1𝛽, and IL-6, along with its significant decrease in serum levels of NO and PGE2. Conclusions These results suggest that YSJTU may exert anti-arthritic effect, at least in part, by inhibiting macrophage-mediated joint inflammation.

• 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.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.3
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• pp.39-50
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• 2014

Objectives The objective of this study is to investigate the protective effects of Banggi-eum (FangchiYin) on the articular cartilage injuries in rat model of osteoarthritis. Methods Articular cartilage injury was induced by injection of monosodium iodoacetate (MIA) (0.25 mg) into both knee joint cavities of rats. Rats were divided into control group (n=8) and Banggi-eum (FangchiYin) group (n=8), which was taken extracts of Banggi-eum (FangchiYin) by orally for 20 days. At the end of the experiment (20 days after MIA injection), gross and histopathological examinations on the articular structures of knee joints were performed. Proteoglycan (PG) content in articular cartilages was analyzed by safranin O staining method. And also, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL-$1{\beta}$) contents in synovial fluid were measured by ELISA method. Results 1. Grossly, the degree of articular cartilage injury in the Banggi-eum (FangchiYin) group was alleviated compared with the control group. 2. PG content in articular cartilage of the Banggi-eum (FangchiYin) group was increased significantly compared with the control group. 3. Histopathologically, osteoarthritic score of the Banggi-eum (FangchiYin) group was decreased significantly compared with the control group. 4. TNF-${\alpha}$ and IL-$1{\beta}$ content in synovial fluid of the Banggi-eum (FangchiYin) group was increased compared with the control group. But there was no significance. Conclusions On the basis of these results, we suggest that Banggi-eum (FangchiYin) have inhibiting effects on the progression of articular cartilage injury in MIA-induced osteoarthritis model.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.129-136
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• 2016

This study was performed to investigate whether an intra-articular injection of transient receptor potential vanilloid 1 (TRPV1) receptor agonist, resiniferatoxin (RTX) would alleviate behavioral signs of arthritic pain in a rat model of osteoarthritis (OA). We also sought to determine the effect of RTX treatment on calcitonin gene-related peptide (CGRP) expression in the spinal cord. Knee joint inflammation was induced by intra-articular injection of monosodium iodoacetate (MIA, $8mg/50{\mu}l$) and weight bearing percentage on right and left hindpaws during walking, paw withdrawal threshold to mechanical stimulation, and paw withdrawal latency to heat were measured to evaluate pain behavior. Intra-articular administration of RTX (0.03, 0.003 and 0.0003%) at 2 weeks after the induction of knee joint inflammation significantly improved reduction of weight bearing on the ipsilateral hindlimb and increased paw withdrawal sensitivity to mechanical and heat stimuli. The reduction of pain behavior persisted for 3~10 days according to each behavioral test. The MIA-induced increase in CGRP immunoreactivity in the spinal cord was decreased by RTX treatment in a dose-dependent manner. The present study demonstrated that a single intra-articular administration of RTX reduced pain behaviors for a relatively long time in an experimental model of OA and could normalize OA-associated changes in peptide expression in the spinal cord.

• The Korea Journal of Herbology
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• v.32 no.2
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• pp.41-47
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• 2017

Objective : The aim of this study is to investigate anti-arthritis activity using a korea's natural monument No. 265 designate 'Yeonsan-Ogye'. In this study, research by using extracts from different concentration of the Yeonsan-Ogye through an MIA-induced arthritis animal model was being conducted in vivo and scientifically verifying the efficacy of medicinal food. Methods : Yeonsan-Ogye was administered 500 mg/kg/day, 1000 mg/kg/day, 2000 mg/kg/day to SD-Rat, where arthritis was induced by monosodium iodoacetate (MIA) at $60mg/m{\ell}$. MMP-9, COMP, CTXII, calcitonin and glycosaminoglycan level in serum were measured by ELISA. The changes of relative hind paw weight bearing ratio by Incapacitance Test Meter and The cartilage of meniscus volume was examined and 3-D high-resolution reconstructions of the cartilage of meniscus were obtained using a Micro-CT system. Also, the histopathological analysis of knee was observed by H&E and safranin-O staining. Results : Production of MMP-9, COMP (all groups) and CTXII (500, 1000 mg/kg/day) level in serum was decreased, respectively, in comparison with control. The other way, production of calcitonin (500, 1000 mg/kg/day) and glycosaminoglycan (all groups) level in serum, Hind paw weight bearing ratio (all groups) was increased, espectively, in comparison with control. The cartilage of patella volume in micro-CT increased significantly. In addition, all groups showed a increase in the cartilage volume and proteoglycan. Conclusion : The results for Yeonsan-Ogye showed significant antiarthritis activity in serum and the cartilage. Therefore, it is thought to be that Yeonsan Ogye can be utilized as a variety of new korea medicie and health foods against arthritis diseases.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.265-273
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• 2016

BACKGROUND/OBJECTIVES: The inhibitory effect of Hijikia fusiforme (HF) extracts on degenerative osteoarthritis was examined in primary cultured rat cartilage cells and a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. MATERIALS/METHODS: In vitro, cell survival and the expression of matrix metalloproteinases (MMPs), collagen type I, collagen type II, aggrecan, and tissue inhibitor of metalloproteinases (TIMPs) was measured after $H_2O_2$ ($800{\mu}M$, 2 hr) treatment in primary chondrocytes. In vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats, and then RH500, HFE250 and HFE500 were administered orally once a day for 28 days. To determine the anti-inflammatory effects of HFE, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) expression were measured. In addition, real-time PCR was performed to measure the genetic expression of MMPs, collagen type I, collagen type II, aggrecan, and TIMPs. RESULTS: In the in vitro assay, cell survival after $H_2O_2$ treatment was increased by HFE extract (20% EtOH). In addition, anabolic factors (genetic expression of collagen type I, II, and aggrecan) were increased by HFE extract (20% EtOH). However, the genetic expression of MMP-3 and 7, known as catabolic factors were significantly inhibited by treatment with HFE extract (20% EtOH). In the in vivo assay, anabolic factors (genetic expression of collagen type I, II, aggrecan, and TIMPs) were increased by oral administration of HFE extract. However, the genetic expression of MMP-3 and 7, known as catabolic factors, and production of NO and $PGE_2$ were significantly inhibited by treatment with oral administration of HFE extract. CONCLUSION: HFE extract inhibited articular cartilage degeneration through preventing extracellular matrix degradation and chondrocyte injury.

• 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.

• 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 Acupuncture Research
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• v.32 no.1
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• pp.53-66
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• 2015

Objectives : This study was designed to investigate effects of Curculiginis Rhizoma pharmaco-acupuncture at $ST_{36}$ on monosodium iodoacetate-induced osteoarthritic rats. Methods : Twenty rats were divided into four groups consisting of 5 rats: rats receiving no injection(normal), rats injected with monosodium Iodoacetate(MIA, control), rats injected with MIA and normal saline(N-S), and rats injected with MIA and Curculiginis Rhizoma (CRPA). N-S and CRPA were administered once a day at $ST_{36}$ during 21 days. After that we examined the weight-bearing ability of hind paws, liver and kidney function, immunocell, cytokines, proteins, and gene expression of cytokines. Injury of synovial tissue was measured by H & E, Safranin O immunofluorescence. Results : The weight-bearing ability of the hind paws, Serum TNF-${\alpha}$, IL-$1{\beta}$, IL-6, PGE2, LTB4, DPD, Osteocalcin, Protein COX-2 of CRPA decreased significantly. Protein Arachidonate 5 lipoxygenase of CRPA was decreased, but not significantly. Expression of gene COX-2, TNF-${\alpha}$, IL-$1{\beta}$, IL-6, NOS2 of CRPA decreased. In histological observations, CRPA was improved, compared with other control groups. Conclusions : It can be suggested that Curculiginis Rhizoma pharmaco-acupuncture at $ST_{36}$ has anti-inflammatory and pain relief effects on monosodium iodoacetate-induced osteoarthritic rats.