• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.163-172
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• 2018

PRF001 is a fragmented DNA polymer extracted from the testes of salmon. The purpose of this study was to assess the anti-inflammatory effect of PRF001 in vitro as well as the protective effect of PRF001 intake against arthritis in a rat model. In vitro, cell survival and inflammatory markers after $H_2O_2$ treatment to induce cell damage were investigated in CHON-001 cells treated with different concentrations of PRF001. In vivo, osteoarthritis was induced by intra-articular injection of monosodium iodoacetate (MIA) into the knee joints of rats. After consumption of PRF001 (10, 50, or 100 mg/kg) for 4 weeks, inflammatory mediators and cytokines in articular cartilage were investigated. In vitro, the levels of inflammatory markers, $IL-1{\beta}$, $TNF-{\alpha}$, COX-2, iNOS, and PGE2, were significantly suppressed by PRF001 treatment. In vivo, the inflammatory mediators and cytokines, $IL-1{\beta}$, p-Erk1/2, $NF-{\kappa}B$, $TNF-{\alpha}$, COX-2, and PGE2, as well as MMP3 and MMP7, which have catabolic activity in chondrocytes, were decreased in the MIA-induced osteoarthritic rats following intake of PRF001. Histological analysis revealed that PRF001 had a protective effect on the articular cartilage. Altogether, these results demonstrated that the anti-inflammatory property of PRF001 contributes to its protective effects in osteoarthritis through deregulating $IL-1{\beta}$, $TNF-{\alpha}$, and subsequent signals, such as p-Erk1/2, $NF-{\kappa}B$, COX-2, PGE2, and MMPs.

• 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.

• 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.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.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.

• Korean Journal of Plant Resources
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• v.28 no.5
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• pp.591-599
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• 2015

Osteoarthritis (OA) is a degenerative disease characterized by the progressive degradation of joint cartilage and is accompanied by secondary inflammation of synovial membranes. The purpose of this study describes a preliminary evaluation of the anti-inflammatory activity on test material of Litsea japonica. fruit (LJTM) Also, this study was to evaluate the effects of LJTM on the joint cartilage of rat with OA induced by monosodium iodoacetate (MIA). To study for anti-inflammatory agents effectively, we first examined the inhibitory effect of the LJTM on the production of pro-inflammatory factors and cytokines stimulated with lipopolysaccharide. We identified anti-nociceptive effects of the LJTM by using in vivo peripheral and central nervous pain models. In addition, the aim of this study was to evaluate the effects on mRNA expression of MMP-2, -3, -7, -9, -13, TIMP-1 and –2 in cartilage of OA. In the LJTM inhibited production of pro-inflammatory mediators (NO and PGE₂) and pro-inflammatory cytokines (TNF-α and IL-6). In cartilage, Expression of MMPs and TIMPs mRNA was suppressed in LJTM treatment group than in the control group. This study suggests that LJTM are potential candidates as anti-inflammation and anti-osteoarthritis agents (painkillers) for the treatment of OA.

• 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.

• 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.

• 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.