• Korean Journal of Clinical Pharmacy
• /
• v.27 no.4
• /
• pp.250-257
• /
• 2017

Objective: The prevalence rate of osteoarthritis in Koreans aged 50 years or older is 14.3%, and the total amount of medical costs is more than KRW 1 trillion. Recently, the reimbursement guidelines for osteoarthritis treatment have changed. Methods: In this study, we sought to describe prescription patterns of nonsteroidal anti-inflammatory drugs (NSAIDs) and gastro-protective agent (GPA) and analyze the clinical and economic impacts of the new policy using the national health insurance claims data. The incidence of upper gastrointestinal adverse event by policy change was identified through the odds ratio, and changes in medicine and medical costs related to osteoarthritis through mean and median. Results: There were 204,552 patients before the reimbursement guidelines relaxation and 239,710 after it, a 17.2% rise. The prescription ratio was 3.3% for the patients prescribed with COX-2 selective NSAIDs alone and 1.3% for those with both COX-2 selective NSAIDs and GPA combination before the reimbursement guidelines relaxation. The reimbursement guidelines relaxation significantly increased their ratios to 6.9% and 2.8%, respectively. Gastrointestinal adverse events significantly reduced by 1.21%p after reimbursement guidelines relaxation. The average medicine cost per person increased significantly to KRW 140,291 from KRW 137,323 after the reimbursement guidelines relaxation, while the average medical cost per person slightly decreased from KRW 311,605 to KRW 310,755 after the relaxation, showing no meaningful difference. Conclusion: The reimbursement guidelines relaxation may influence on decreasing the upper gastrointestinal adverse event, increasing the medicine costs and maintaining the medical costs for osteoarthritis.

• Preventive Nutrition and Food Science
• /
• v.21 no.4
• /
• pp.310-316
• /
• 2016

In this study, the anti-osteoarthritis effects of Cynanchum wilfordii, Phlomis umbrosa, and Angelica gigas extract (CPAE), observed and confirmed in previously clinical studies were further investigated by in vitro and in vivo studies. Anabolic biomarkers related to healthy cartilage maintenance, such as aggrecan, type II collagen ${\alpha}$-1 (Col2a1), sex determining region Y-box-9 (Sox-9), and catabolic biomarkers related to osteoarthritis, such as cyclooxygenase-2 (Cox-2), matrix metalloproteinase-13 (Mmp13), and nuclear factor kappa-light-chain-enhancer of activated B cells ($Nf{\kappa}b$), were evaluated by quantitative reverse transcriptase polymerase chain reaction and reporter gene assay. In vitro study results showed significant changes in both anabolic and catabolic biomarkers. For anabolic factors, significant changes in the level of aggrecan (P<0.05), Col2a1 (P<0.05), and Sox-9 (P<0.01) activation were shown after treatment of cartilage cells with CPAE (50 ng/mL) with similar efficacy compared to insulin growth factor, the positive control (100 ng/mL). For catabolic factors, significant changes in the inhibition activity of Cox-2 (P<0.05), Mmp13 (P<0.01), and $Nf{\kappa}b$ (P<0.05) were shown for CPAE (50 ng/mL) with similar efficacy compared to Celecoxib, the positive control ($10{\mu}M$). In the in vivo carrageenan-induced paw edema model study results showed that CPAE-treated groups (100 mg/kg) and Celecoxib-treated groups (60 mg/kg) showed comparably significant efficacy of inhibition by 37.1% and 52.1%, respectively. Furthermore, CPAE (200 mg/kg) showed similar effect to Celecoxib (60 mg/kg) with an inhibition rate of 54.3%. This result confirms that CPAE effectively inhibited the inflammation-induced osteoarthritis symptoms.

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

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

• Korean Journal of Pharmacognosy
• /
• v.36 no.4 s.143
• /
• pp.338-343
• /
• 2005

Inflammatory mediators such as interleukin-1 (IL-1), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}),\;interferon-{\gamma}\;(IFN-{\gamma})$ and lipopolysaccharide (LPS) are thought to play major roles in joint diseases such as a rheumatoid arthritis (RA), and there is considerable evidence playing a role for these cytokines in osteoarthritis (OA). Therefore, we have studied the effects on anti-inflammation and analgesic by ethyl acetate fraction from 70% ethanol extract of Artemisia capillaries (EAC). As a positive control, apigenin, which is known as an anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect. EAC showed strong inhibitory efficacy against cytokine-induced proteoglycan degradation, $PGE_2$ production, nitric oxide (NO) production, and matrix-matalloproteinases (MMPs) expression in rabbit articular chondrocyte. In the writhing test induced by acetic acid, EAC $(200{\sim}400\;mg/kg)$ exhibited a dose-dependent inhibition of writhing. The results indicate that EAC have anti-inflammatory and analgesic activities, and could be a good herbal medicine candidate for curing of RA and/or OA.

• Korean Journal of Plant Resources
• /
• v.28 no.5
• /
• pp.591-599
• /
• 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 Korean Medicine Rehabilitation
• /
• v.25 no.2
• /
• pp.15-35
• /
• 2015

Objectives This study was performed to investigate the effects of Bujasasim-tang ethanol extract (BST) on oxidative stress, inflammation and osteoarthritic rat model. Methods To ensure safety of BST, heavy metal levels were measured and cytotoxicity test was done. In vitro, To evaluate antioxidative effects of BST, total phenolic contents, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) scavenging activity, reactive oxygen species (ROS) levels were measured. Also, to evaluate anti-inflammatory effects of BST treated group, total nitric oxide (NO) and pro-inflammatory cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$) levels were measured in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In vivo, We injected MIA $50{\mu}l$ (60 mg/ml) into knee joints of rats to induce osteoarthritis. Rats were divided into total 3 groups (normal, control, BST treated group, each n=7). Normal group was not treated at all without inducing osteoarthritis and taken normal diet. Control group was induced osteoarthritis by MIA and taken with 2 ml of distilled water once a day for 4 weeks. BST treated group was induced osteoarthritis by MIA and taken BST 2 ml (200 mg/kg/mouse) once a day for 4 weeks. We evaluated dynamic weight bearing with the Incapacitance Test Meter. At the end of experiment, the rats were sacrificed to observe the functions of liver and kidney, changes of WBC, neutrophil, lymphocyte, monocyte levels in blood, to evaluate the levels of pro-inflammatory cytokines, tissue inhibitor of metallopreteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), prostaglandin $E_2$ ($PGE_2$), leukotriene $B_4$ ($LTB_4$) within serum. We observed change of articular structures by Hematoxylin & Eosin (H&E), safranin-O staining method and measured amount of cartilage by micro CT-arthrography. Statistical analysis was done by unpaired student's t-test with significance level at p<0.05 in SPSS 11.0 for windows. Results 1. Safety of the BST was identified. 2. AST, ALT, BUN, creatinine levels of BST treated group were within normal limit. In vitro, 1. DPPH and ABTS free radical scavenging activities of BST showed dose-dependent increase. 2. ROS production were significantly decreased. 3. Total nitric oxide (NO) and IL-$1{\beta}$ production were decreased. 4. IL-6 and TNF-${\alpha}$ production were significantly decreased. In vivo, 1. Weight bearing ability was significantly increased. 2. WBC, neutrophil, lymphocyte, monocyte levels in blood were decreased. 3. IL-$1{\beta}$ and TNF-${\alpha}$ levels in serum were significantly decreased. and the IL-6 level was decreased. 4. TIMP-1, MMP-9, $LTB_4$, $PGE_2$ levels in serum were significantly decreased. 5. Cartilage volume of BST treated group was significantly increased. Also changes of cartilage, synovial membrane, fibrous tissue were suppressed. Conclusions The results obtained in this study Bujasasim-tang have effects of antioxidative, anti-inflammatory, relieve pain and protection of cartilage. Therefore we expect that Bujasasim-tang is effective treatment for osteoarthritis.

• Journal of Preventive Medicine and Public Health
• /
• v.37 no.2
• /
• pp.150-156
• /
• 2004

Objectives : To investigate the utilization patterns of non-steroidal anti-inflammatory drugs (NSAIDs) among the elderly with osteoarthritis (OA) undergoing primary ambulatory care in Busan metropolitan city, Korea. Methods : OA patients, aged 65 years and over, were identified from the Korean National Health Insurance Review Agency drug prescription database. The subjects had at least one episode of claim for OA (ICD-10-CM: M15-M19) between August 1, 2000 and February 28, 2002. Trends in the determinations of NSAIDs utilization were identified using chi-squared tests for trend. Results : There were 47,711 osteoarthritic patients. The total number of visits by these patients was 177,443, with a total frequency for NSAID prescriptions of 214,952. Seventy-nine percent of the OA patients were female. NSAIDs were prescribed on 133,284 visits (75.1%) and the proportion of prescriptions was significantly increased with age. Only the proportion of visit when NSAIDs were prescribed decreased, from 65.1 to 43.5%, during the study period (p<0.001). However, the proportion of combined treatments with anti-ulcer drugs was increased. The use of NSAIDs injections was decreased. Of the individual NSAIDs, diclofenac (28.7% of total frequency of NSAID prescriptions), piroxicam (15.0%) and talniflumate (8.7%), were the most frequently prescribed. Among the NSAIDs prescribed OA visits, 45.7% used two or more NSAIDs. Conclusion : The total proportion of NSAIDs prescribed to the osteoarthritic patients was higher than in other studies. The decline in the use of NSAIDs during the study period, and the frequent selection of safer medications, such as combination therapy with anti-ulcer drug, may reflect the risk awareness of the use of NSAIDs.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.04a
• /
• pp.8-8
• /
• 2018

Muscle atrophy, known as a sarcopenia, is defined as a loss of muscle mass resulting from a reduction in muscle fiber area or density due to a decrease in muscle protein synthesis and an increase in protein breakdown. Many conditions are associated with muscle atrophy, such as aging, denervation, disuse, starvation, severe injury and inflammation, prolonged bed rest, glucocorticoid treatment, sepsis, cancer, and other cachectic diseases. On the other hand, osteoarthritis (OA) is the most common form of joint disease and is wide spread in the elderly population and is characterized by erosion of articular cartilage, osteophyte formation, and subchondral bone sclerosis. The cytokine network plays an important role in the development and progression of OA with the inflammatory cytokine. Schisandrae Fructus (SF) derived from the ripe fruit of Schisandra chinensis (Turcz.) Baill. (Magnoliaceae) has been extensively used in traditional herbal medicines in Asia. It was originally used as a tonic and has been traditionally used for the treatment of many uncomfortable symptoms, such as cough, dyspnea, dysentery, insomnia, and amnesia for a long time. Previous reports have shown that SF and its related compounds possess various biological activities such as antioxidant, anti-inflammatory, anticancer, anti-microbial, antiseptic, anti-aging, hepatoprotective and immunostimulating effects. However, the therapeutic effects of SF on muscle atrophy and OA has not yet been evaluated. In the present study, we aimed to determine whether extracts of SF, the dried fruit of S. chinensis, mitigates the development of muscle atrophy and OA.

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