• 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.

• The Korea Journal of Herbology
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• v.34 no.4
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• pp.27-35
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• 2019

Objectives : Osteoarthritis is characterized by degeneration of articular cartilage, which is characterized by chronic pain, stiffness and decrease range of motion. The present study was designed to compare the therapeutic effect of Dioscoreae Rhizoma water extract (DRW) and Dioscoreae Rhizoma 30% ethanol extract (DRE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : Osteoarthritis was induced by injection of MIA ($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. After adaptation period for seven days, rats were divided by 5 groups (n=10/group): normal group, control group, positive control (indomethacin 5 mg/kg), DRW 200 mg/kg treated group, DRE 200 mg/kg treated group (n=10/group). The hind paw weight distribution was measured with the changes of reactive oxygen species (ROS), peroxynitrite ($ONOO^-$) in articulation tissue. Also, the cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factoralpha ($TNF{\alpha}$), interleukin-6 (IL-6), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot analysis. Results : The administration of DRW and DRE significantly decreased the hind paw weight distribution. The ROS and $ONOO^-$ levels of cartilaginous tissue were significantly decreased in DRW and DRE compared to control group. The results showed that DRE decreased inflammatory cytokines such as iNOS and $TNF{\alpha}$. Also DRE decreased MMP-1 and increased TIMP-1. Conclusions : Based on the above results, Dioscoreae Rhizoma extract seems to have the therapeutic effect on osteoarthritis via suppression of inflammation.

• The Korea Journal of Herbology
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• v.35 no.1
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• pp.35-44
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• 2020

Objectives : The objective of this study was to investigate the therapeutic effect of Corni Fructus 30% ethanol extract (CFE) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The subjects were divided into 4 groups ; Normal group (N, n=10), MIA-induced osteoarthritis control group (Con, n=10), indomethacin 5 mg/kg treated group (INDO, n=10), CFE 200 mg/kg treated group (CFE, n=10). Blood and articulation tissues were collected after two weeks of drug administration. Oxidative stress was analyzed with reactive oxygen species (ROS), peroxynitrite (ONOO-). And the Nuclear factor erythroid-2 (Nrf2), heme oxygenase-1 (HO-1), superoxide dismutase (SOD), catalase, glutathione peroxidase-1/2 (GPx-1/2), Nuclear Factor Kappa B p65 (NF-κBp65), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), Interleukin 1β (IL-1β), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were investigated by western blot. Results : The administration of CFE showed a significant reduction of changes in relative hind paw weight distribution. Reactive oxygen species (ROS) and peroxy nitrite (ONOO-) levels of articulation tissues were significantly decreased in CFE compared to the control group. Western blot measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2 showed that the CFE group was increased compared to the Con group. And western blot measurements of NF-κBp65, COX-2, iNOS, TNFα, IL-6, IL-1β showed that the CFE group was reduced compared to the Con group. Also CFE group decreased MMP-1 and increased TIMP-1. Conclusion : Based on the above results, it can be seen that osteoarthritis is improved when Corni Fructus 30% ethanol extract treated.

• Korean Journal of Acupuncture
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• v.39 no.4
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• pp.152-171
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• 2022

Objectives : This study was designed to investigate the effects of Sunbanghwalmyung-eum gamibang on Monosodium iodoacetate-induced osteoarthritis rats. Methods : Forty Sprague-Dawley (SD) rats were divided into 5 groups of 8 rats each. Osteoarthritis (OA) was induced by injecting MIA (2 mg/50 µl) into the joint cavity of the left knee of SD rats belonging to the experimental group, and normal saline was injected into the joint cavity of the left knee instead of MIA in the normal group. To the normal group and the controlled group (OA group), 2 ml of distilled water was orally administered. To the positive control group (Indomethacin group), indomethacin 2 ml at a concentration of 2 mg/kg, to the low concentration group of SHG (Low group), 2 ml of SHG at a concentration of 2 mg/kg, and to the high concentration group of SHG (High group), 2 ml of SHG at a concentration of 4 mg/kg ml was orally administered. The drug was administered for a total of 4 weeks, and histological changes were analyzed by Hematoxylin-Eosin staining and Safranin-O staining. In addition, inflammatory cytokines such as TNF-α, IL-1β, and IL-6, and MMP-13, TIMP-1, and GAGs were immunohistochemically analyzed. Finally, hematological examination, blood biochemical examination, and liver and kidney biopsy were performed. Results : SHG groups (Low and High) inhibited the matrix destruction and damage of the knee joint cartilage in SD rat model, and significantly prevented the reduction in cartilage thickness. In SHG groups, the expressions of TNF-α, IL-1β, IL-6 and MMP-13 were significantly decreased, and the expressions of TIMP-1, GAGs were significantly increased compared with OA group. The safety indicators had no significant differences among five groups. Conclusions : These results show that SHG has cartilage protection capacity, anti-inflammatory effect.

• Journal of the Korean Applied Science and Technology
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• v.38 no.2
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• pp.368-377
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• 2021

The present study aimed to evaluate the effects of radiation mutant Perilla frutescens var. crispa and Atractylodes macrocephala Koidzumi complex extract(Perilla frutescens var. crispa complex extract) on the mediators related to degenerative arthritis in a monosodium iodoacetate-induced rat model of degenerative arthritis. Perilla frutescens var. crispa complex extract 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 Perilla frutescens var. crispa complex extract for another 4 weeks. It was evaluated that the treatment effects based on serum bio-markers, and morphological and histopathological analysis of the knee joints. Compared with those in negative control rats, the Perilla frutescens var. crispa complex extract treatments significantly reduced the serum levels of inflammation, bone metabolism markers (i.e., TNF-α, MMP-3, COX-2, PGE₂, COMP, and Aggrecan). Otherwise, it was significantly increased the production of CTX-2 in cartilage absorption mediators. In addition, the Perilla frutescens var. crispa complex extract treatments effectively preserved the knee cartilage and synovial membrane. As a result, it indicates that the Perilla frutescens var. crispa complex extract improved degenerative arthritis symptoms. Thus, the Perilla frutescens var. crispa complex can be used in food material for the management of degenerative arthritis.

• 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.

• 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.

• 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 the Korean Society of Food Science and Nutrition
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• v.43 no.1
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• pp.30-39
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• 2014

HanPoong Leading (HPL)-04 were prepared with different oriental medicines (balk of Kalopanax pictus balk, Chaenomelis Fructus, Angelica gigas root, Zingiber officinale, Raphanus sativus Linne and Saururus chinensis Baill.) to investigate the protective effects of HPL-04 on cartilage degradation in knee osteoarthritis (OA). Rat articular chondrocytes incubated with rhIL-$1{\alpha}$ markedly increased matrix metalloproteinase (MMP)-2 and 9 activities, decreased cell viability and reduced chondrogenic gene expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, MMP-2 and 9 activities and real time RT-PCR indicated that HPL-04 counteracted these harmful effects in dose-dependent manner. In addition, for experimental OA in vivo, monosodium iodoacetate (MIA, 0.5 mg/50 ${\mu}L$) was injected into knee joints of rats and administered HPL-04 to rats for 4 consecutive weeks after MIA treatment. The experimental data showed that treatment with HPL-04 significantly prevented of MMP-2 and 9 activities in articular cartilage. Histopathological and micro-CT evaluations of the knee joints also revealed that HPL-04 effectively ameliorated MIA-induced degenerative OA. In conclusion, HPL-04 has potential applicability for the prevention and treatment of degenerative OA.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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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.