• Title/Summary/Keyword: Monoiodoacetate

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Ginsenoside Rb1 inhibits monoiodoacetate-induced osteoarthritis in postmenopausal rats through prevention of cartilage degradation

  • Aravinthan, Adithan;Hossain, Mohammad Amjad;Kim, Bumseok;Kang, Chang-Won;Kim, Nam Soo;Hwang, Ki-Chul;Kim, Jong-Hoon
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.287-294
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    • 2021
  • Background: Ginsenoside Rb1 (G-Rb1), one of the major active compounds in Panax ginseng, has already been shown to reduce inflammation in various diseases. Osteoarthritis (OA) has traditionally been considered a degenerative disease with degradation of joint articular cartilage. However, recent studies have shown the association of inflammation with OA. In the present study, we investigated whether Rb1 had an antiinflammatory effect on monoiodoacetate (MIA)-induced OA in ovariectomized rats as a model of postmenopausal arthritis. Methods: G-Rb1 at a dosage of 3 and 10 ㎍/kg body weight was administered every 3 days intraarticularly for a period of 4 weeks to observe antiarthritic effects. Diclofenac (10 mg/kg) served as a positive control. Results: The administration of Rb1 significantly ameliorated OA inflammatory symptoms and reduced serum levels of inflammatory cytokines. Furthermore, G-Rb1 administration considerably enhanced the expression of bone morphogenetic protein-2 and collagen 2A and reduced the levels of matrix metalloproteinase-13 genes, indicating a chondroprotective effect of G-Rb1. G-Rb1 also significantly reduced the expression of several inflammatory cytokines/chemokines (interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1)/CCL-2, interleukin [IL]-1β, and IL-6). Histological analysis demonstrated that G-Rb1 significantly attenuated the pathological changes in MIA-induced OA in ovariectomized rats. Safranin O and toluidine blue staining further demonstrated that G-Rb1 effectively prevented the degradation of cartilage and glycosaminoglycans, respectively. Conclusion: Overall, our results suggest that G-Rb1 exerts cartilage protective effect on MIA-induced ovariectomized OA rats, by inhibiting inflammatory mediators such as IL-6, IL-1β, MCP-1/CCL-2, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2). These results shed a light on possible therapeutic application of G-Rb1 in OA.

Enzymatic Properties of Extracellular Cytosine Deaminase (세포외 Cytosine Deaminase의 효소학적 성질)

  • 유대식;김대현;박정문;송형익;정기택
    • Korean Journal of Microbiology
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    • v.26 no.4
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    • pp.368-374
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    • 1988
  • Enzymological proprties of an extracellular cytosine deaminase from Bacellus polymyxa YL 38-3 were investigated. The extracellular enzyme was very stable, and optimum pH and temperature for the enzyme activity were found to be near pH 6.0 in 0.2M potassium phosphate buffer and at $30^{\circ}C$, respectively. 5-Fluorocytosine was converyed to 5-fluorouracil by the enzyme, but 5-methylcytosine was not to thymine by it. The enzyme activity was completely inhibited by some heavy metal ion such as 1mM of $Cd^{2-}$ and $Hg^{2+}$, and by 1mM of p-chloromercuribenzoate, respectively. The enzyme activity was inactivated about 75% by 1mM of o-phenanthroline and monoiodoacetate. But the enzyme activity was stimulated up to 200% by 1mM of 2-mercaptoethanol.

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Comparison of Piroxicam Pharmacokinetics and Anti-Inflammatory Effect in Rats after Intra-Articular and Intramuscular Administration

  • Park, Chan Woong;Ma, Kyung Wan;Jang, Sun Woo;Son, Miwon;Kang, Myung Joo
    • Biomolecules & Therapeutics
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    • v.22 no.3
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    • pp.260-266
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    • 2014
  • This study evaluated the pharmacokinetic profile and therapeutic efficacy of piroxicam (PX), a long acting non-steroidal anti-inflammatory drug for the treatment of arthritis, following intra-articular (IA) injection in comparison to the pharmacokinetic profile and therapeutic efficacy of PX after intramuscular (IM) injection. In the pharmacokinetic study in rats, systemic exposure and pharmacokinetic parameters of PX after a single IA dose were compared with systemic exposure and pharmacokinetic parameters of PX after administration of the same dose IM (0.6 mg/kg). The anti-inflammatory and analgesic effects of IA PX were evaluated simultaneously in a monoiodoacetate-induced osteoarthritis rat model. The plasma PX concentration rapidly rose following IA injection, and it was comparable to the plasma PX concentration following IM injection, suggesting the rapid efflux of the drug molecule from the joint cavity. However, in the efficacy study, the IA PX administration significantly reduced the knee swelling by reducing the level of prostaglandin $E_2$ in the joint, compared to that following administration of IA vehicle and after administration of the IM PX dose. In addition, we found that the anti-inflammatory and anti-nociceptive efficacies of IA PX were synergistically increased upon co-treatment with hyaluronic acid (HA), a potent agent for the treatment of osteoarthritis, at the weight ratio of 1:1 or 1:2, and these effects were more pronounced than those following administration of HA or PX alone. In conclusion, this study demonstrated the efficacy of the IA use of PX alone and/or in combination with HA in osteoarthritis.

Protective Effects of Bogol-tang on Monosodium Iodoacetate-induced Osteoarthritis and Interleukin-1β-treated Primary Chondrocytes (보골탕이 Monosodium Iodoacetate 유도 골관절염과 Interleukin-1β 유도 연골세포에 미치는 보호 효과)

  • Sung, Jin Wook;Lee, Hai Woong;Kang, Kyung Hwa;Kim, Kyoung Min;Cho, Sung Woo
    • 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.

Effect of Mixed Extract of Panax Notoginseng, Rehmanniae Radix and Acanthopanacis Cortex (AIF) on Experimentally Induced Osteoarthritis

  • Park, Shin-Ae;Kim, Jae-Hoon;Ahn, Jeong-Taek;Kim, Won-Tae;Park, Chull-Gyu;Jeong, Man-Bok;Yi, Sun-Shin;Yoon, Yeo-Sung;Yoon, Jung-Hee;Kim, Hyung-Gun;Seo, Kang-Moon
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.426-432
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    • 2010
  • The objective of the present study was to evaluate the effect of a mixed extract of three herbs, Panax Notoginseng, Rehmanniae Radix and Acanthopanacis cortex (AIF), for the treatment of horses with experimentally induced osteoarthritis. Twelve healthy male horses were included in this study. Horses were assigned to one of two groups: the AIF group (n=6) or the control group (n=6). Osteoarthritis was induced in all horses by intraarticular injection of sodium monoiodoacetate (0.12 mg/kg). Horses in the AIF group received 3 g of AIF with food daily, and those in the control group received food only. Treatment began on the day of intraarticular injection. Clinical and radiographic evaluations were performed every 2 weeks. At week 12, horses were euthanatized, and postmortem gross pathologic and histologic examinations of the middle carpal joint were performed. There were no significant differences in clinical values between the two groups. Radiographic evaluation revealed that the percentages of narrowness of joint space width in the control group were significantly higher than those in the AIF group (p<0.02). On gross pathologic examination, the mean total dimensions of articular cartilage erosions and fibrillations in the control group ($101.5{\pm}41.5mm^2$) were significantly wider than those in the AIF group ($29.3{\pm}39.7mm^2$; p<0.01). On histopathologic evaluation, significantly higher grades of staining intensity and lower empty lacunae (EL) ratios were found in the AIF group (p<0.03). The present study revealed that AIF had significant disease modifying effects in horses with experimentally induced osteoarthritis.

Effect of Growth Regulators on th Growth and Vitamin C Biosynthesis During Germingation of Soybean (콩나물 생장과 비타민C의 생합성에 대한 생장조절제의 영향)

  • Kim, Sang-Ock
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.17 no.2
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    • pp.115-124
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    • 1988
  • This study was carried out to realize the effect of gibberllic acid$(GA_3)$, 1-naphthaleneacetic acid(NAA) and indole-3-acetic acid(IAA) on the biosynthesis of vitamin C. The relation between carbohydrate metabolism and vitamin C production in soybean sprouts was also investigated. Growth, vitamin C content, protein, galactonolactone dehydrogenase(GLD), ribulose diphosphate carboxylase(RuDpCO) and RNA level in the plastid and cytoplasm were determined. The effects of protein and respiratory inhibitors on the growth and vitamin C production were also examined. The most favourable growth of soybean sprouts was observed at the level of NAA $10^{-8}M,\;IAA10^{-6}M\;and\;GA_3\;10^{-5}M$ in the single treatment, respectively, and also favourable at levels of $GA_3\;10^{-5}M+NAA\;10^{-9}M\;and\;GA_3\;10^{-5}M+IAA\;10^{-9}M$ in the case of mixed treatment. The excellent growth was observed at the level IAA $10^{-6}M$ among all the single and mixed treatments. When the soybean sprouts were treated with NAA $10^{-8}M,\;IAA\;10^{-6}M\;GA_3\;10^{-5}M,\;GA_3\;10^{-8}M+IAA\;10^{-6}M,\;and\;GA_3\;10^{-5}M+IAA\;10^{-9}M$, the maximum growth rate was observed at the level of IAA $10^{-6}M$ and the conten of vitamin C was 24.26mg% which was 1.6 times higher than that of the control. RuDpCO was inhibited by the chloramphenicol at the concentration that did not inhibit the growth but the activities of NADP-GDH, GLD and vitamin C content were not affected. These results showed that the biosynthesis of viamin C had nothing to do with the activity of chloroplastic RNA but with cytoplasm. The highest vitamin C content was found at the the level of IAA $10^{-6}M$, where the GLD activity increased up 1.8 times of the control. The concentration of IAA $10^{-6}M$ promoted the biosynthesis of RNa and protein both in chloroplast and cytoplasm, especially in the cytoplasm. Thus it suggeted that IAA affected vitamin C biosynthesis by regulating RNA level in the cytoplasm. 2,4-Dinitrophenol as an uncoupler of oxidative phosphorylation did not inhibit the vitamin C biosynthesis, however, all of the respiratory inhibitors severely inhibited the growth and vitamin C biosynthesis.

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