• Journal of Nutrition and Health
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• v.56 no.3
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• pp.231-246
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• 2023

Purpose: The aim of this study was to investigate the anti-osteoarthritic effect of the ethanol extract of Boswellia serrata gum resin (FJH-UBS) enriched with keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid compared to the conventional Boswellia serrata extract by adding the process of removing oil with hexane, in the monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods: Sprague-Dawley (SD) rats were orally administered 0, 40, or 80 mg of FJH-UBS/kg body weight (BW)/day for 5 weeks and injected with MIA intra-articularly into right knee joints on day 15 to induce osteoarthritis. Changes in the knee joint microarchitecture, cartilage degradation, the expression of inflammatory mediators, cytokines, and matrix metalloproteinases (MMPs) in serum and synovia were observed. Results: Oral administration of FJH-UBS (80 mg/kg BW/day) reduced MIA-induced knee swelling and cartilage degradation and increased the expression of type II collagen and aggrecan in articular cartilage. Furthermore, FJH-UBS administration reduced MIA-induced increases in the serum levels of prostaglandin E2, leukotriene B4, interleukin (IL)-1β, IL-6, and MMP-13, and MIA-induced increases in the mRNA expressions of inducible nitric oxide synthase, cyclooxygenase-2, 5-lipoxygenase, IL-1β, IL-6, TNF-α, MMP-2, MMP-9, and MMP-13 in the synovia of knee joints. Conclusion: These results indicate that FJH-UBS exerts its anti-osteoarthritic effects by suppressing the expressions of inflammatory cytokines and MMPs and, thus, cartilage degradation. Furthermore, they suggest that FJH-UBS has potential use as a functional food that improves joint and cartilage health.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1154-1162
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• 2007

This study was to investigate the effects of Bee-venom Treatment on the monosodium iodoacetate(MIA)- induced osteoarthritis in rats. Arthritis was induced by injection of MIA(0.5 mg) into knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was injected with normal saline once a day for 20 days, while treated group was injected with Bee-venom extract once a day for same duration. Body weights were measured at 0, 5, 10, 15, 20 days after injection. At the end of experiment, gross and histopathological examination on the articular cartilages of the knee joints were performed. Proteoglycan contents of articular cartilages were analysed by safranine O staining method. The contents of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 in synovial fluids were analysed by ELISA method. And also, COX-2 and iNOS immunohistochemical examination on the knee joints were performed. Body weights of the treated group were increased compared with control group at 20 days after injection. Grossly, the severity of osteoarthritis in the treated group were alleviated compared with control group. PG contents in articular cartilages of the treated group were significantly increased compared with control group. Histopathologically, degenerative and necrotic lesion of articular cartilages in the treated group were alleviated compared with those of the control group. $TNF-{\alpha}$ contents in synovial fluids of the treated group were decreased compared with control group. Positive reactions of COX-2 in chondrocytes and synovial membranes of the treated group were decreased compared with the control group. On the basis of these results, we concluded that Bee-venom treatment has anti-arthritic effects on the monosodium iodoacetate-induced osteoarthritis in rats. And it's effects were related with reduced secretion of $TNF-{\alpha}$ and COX-2 from osteoarthritic chondrocytes and synovial membranes.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.2
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• pp.15-29
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• 2014

Objectives We have studied to know effects of Bangkeehwangkee-tang on the monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of monosodium iodoacetate into knee joint cavity of rats. Rats are devided into 4 groups; Sham, control, Bangkeehwangkee-tang, Shinbaro. Sham group was injected by normal saline into knee joint cavity only. Control group was taken no treatment and Experimental groups were taken extracts of Bangkeehwangkee-tang and Shinbaro by orally once a day for 4 weeks. The content of TNF-$\alpha$, IL- $1{\beta}$ and IL-6 in synovial fluids were analysed. COX-2 in chondrocytes and blood PGE2 concentration were analysed. Histopathological examination was performed by Safranin-O fast green staining and Mankins score checking. Results The content of TNF-$\alpha$, IL-$1{\beta}$ in experimental groups were decreased compared with control group. COX-2 in chondrocytes and blood PGE2 concentration in experimental groups were decreased compared with control group. Histopathologically, osteoarthritic scores of experimental groups were decreased compared with control group. But the content of IL-6 in synovial fluids was not significantly compared with control group. Conclusions According to these results, it can be suggested that Bangkeehwangkee-tang has anti-arthritic effects on the MIA induced osteoarthritis in rats.

• Korean Journal of Pharmacognosy
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• v.49 no.3
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• pp.262-269
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• 2018

Sparassis crispa (Wulf.) is an edible/medicinal mushroom and has been reported to biological activities such as antitumor, anti-angiogenesis, antioxidant and wound healing. However, there have not been many researches on osteoarthritis of S. crispa. The aim of this study was to investigate the effects of S. crispa extract on rats with osteoarthritis induced by MIA. Osteoarthritis is a gradually developmental disease that early stage, causes joint stiffness and complains of joint pain. In addition, it gives rise to edema and hypo-function. The results of this study, S. crispa extract effectively inhibited ROS production, increased the production of antioxidant protein SOD and catalase in knee joint cartilage tissue. In addition, S. crispa extract inhibited the expression of pro-inflammatory cytokines and enzymes such as NOX4 and $P47^{phox}$, which are involved in the expression of COX-2, iNOS and the production of ROS. Also, S. crispa extract inhibited the destruction of synovial tissue, cartilage tissue and proteoglycans in articular cartilage in rats.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.2
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• pp.101-113
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• 2019

Objectives Bogol-tang has clinically been used to protect joint cartilage and to treat osteoarthritis. Our objective was to study the protective effect of Bogol-tang extract (BGT) in functional impairment, behavioral disorders, cartilage loss and pathological changes in a monoiodoacetate (MIA)-induced murine osteoarthritis (OA) model and interleukin (IL)-$1{\beta}$ -treated primary rat chondrocytes. Methods Mouse knee joints were injected with MIA, a chemical that inhibits glycolysis and causes joint inflammation and matrix loss. MIA-OA induced mice orally administered BGT or acetaminophen (AAP) for 18 days by daily. Primary rat chondrocytes were pretreated with BGT or dexamethasone (DEX) and followed by co-incubation with IL-$1{\beta}$ (10 ng/mL). Results In MIA-OA mice model, BGT led to delayed response on hot plate analysis, and suppressed the cartilage loss and damages in joint tissues. BGT suppressed the elevated levels of inflammatory mediators, nitrite and $PGE_2$, the gene expression of matrix degrading enzymes, and extracellular-signal-regulated kinases 1/2 and c-JunN-terminal kinase phosphorylation in IL-$1{\beta}$-treated primary rat chondrocytes. Conclusions Our results suggest that BGT improve the knee joint function and delay the cartilage damages by anti-nociceptive, anti-inflammatory and ant-catabolic effects, which indicate BGT could be a potential candidate for osteoarthritis treatment.

• Journal of the Korean Society of Physical Medicine
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• v.9 no.2
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• pp.151-159
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• 2014

PURPOSE: The purpose of this study was to evaluate whether light-emitting diodes (LED) irradiation could be effective in a noninvasive, therapeutic device for the treatment of osteoarthritis(OA). METHODS: Twenty-four male Sprague-Dawley rats were divided into four groups: Vehicle control (saline); monosodium iodoacetate-injection (MIA); LED irradiation after MIA injection (MIA-LED); indomethacin-treatment after MIA injection (MIA-IMT). OA was induced by intra-articular injection of 3 mg MIA through the patellar ligament of the right knee. Vehicle control rats were injected with an equivalent volume of saline. The LED was irradiated for 15 min/day for a week after 7 days of MIA treatment. To compare with the effect of LED irradiation, the indomethacin was administrated 20 mg/kg twice a week orally after 7 days of MIA treatment. Knee joints were removed and fixed overnight in 10% neutral buffered formalin and decalcified by EDTA for 2 week before being embedded in paraffin. The assessment of OA induction were monitored by knee movement and radiographic finding. Histologic analysis were performed following staining with hematoxylin and eosin, safranin O-fast green, or toluidine blue, picrosirius red, and histologic changes were scored according to a modified Mankin system. Apoptotic cell in tissue sections was detected using TUNEL method. RESULTS: Radiographic examination could not show the differences between the MIA-treated and the MIA-LED-treated rats. In the histologic analysis, however, LED irradiation prevented cartilage damage and subchondral bone destruction, and significantly reduced mononuclear inflammatory cell infiltration and pannus formation. LED irradiation also reduced apoptosis of cartilage cells, but it prevented apoptosis of infiltrated inflammatory cells in synovium. In addition, LED irradiation showed an increase of collagen production in the meniscus. CONCLUSION: These results suggest that the 840 nm LED irradiation would be a suitable non-thermal phototherapy for the treatment of OA, as a cartilage protection and anti-inflammatory modality.

• 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 Korea Journal of Herbology
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• v.33 no.5
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• pp.53-66
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• 2018

Objectives : This study was designed to compare the effects of acanthopanax stem bark (ASB) and acanthopanax root bark (ARB) on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods : The antioxidant activities were evaluated through radical scavenging assays using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Also, we examined total poly phenol and flavonoids contents. Osteoarthritis was caused by injection MIA($50{\mu}{\ell}$ with $80mg/m{\ell}$) into the knee joint cavity of rats. Rats were divided by 4 groups (normal group, control group, ASB treated group, ARB treated group, each n=6). The changes in the levels of reactive oxygen species (ROS), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were analyzed after experiment. Also, the anti-oxidant, inflammatory protein levels were investigated western blot analysis. Knee joint tissue, histopathological observation hematoxylin & eosin staining and safranin-O staining were measured. Results : In the present study, ARB treated group showed superior inhibitory effects on the inflammatory parameters than the ASB treated group. ARB aqueous extract was effective in antioxidant measurements. The administration of ARB showed a significant reduction of changes in relative hind paw weight distribution. Morever, it decreased ROS, ALT and AST levels in serum, compared with those of the control rats. The ARB administration inhibited the biomarkers of inflammatory in tissues. Conclusions : ASB aqueous extract and ARB aqueous extract have a great effect on osteoarthritis, and ARB aqueous extract has excellent effect on osteoarthritis through antioxidant and anti-inflammation.

• 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.

• 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.