• Title/Summary/Keyword: nNOS

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A Formulated Korean Red Ginseng Extract Inhibited Nitric Oxide Production through Akt- and Mitogen Activated Protein Kinase-dependent Heme Oxygenase-1 Upregulation in Lipoteichoic Acid-stimulated Microglial Cells (홍삼추출액은 lipoteichoic acid로 자극된 소교세포에서 Akt 및 MAPK 의존적으로 heme oxygenase-1 발현을 유도함으로써 NO 생성을 억제함)

  • Shin, Ji Eun;Lee, Kyungmin;Kim, Ji-Hee;Madhi, Iskander;Kim, YoungHee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.402-409
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    • 2019
  • Korean red ginseng made from steaming and drying fresh ginseng has long been used as a traditional herbal medicine due to its effects on the immune, endocrine, and central nerve systems and its anti-inflammatory activity. In this study, we investigated the molecular mechanism responsible for the anti-inflammatory effects of a formulated Korean red ginseng extract (RGE) in response to lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria. RGE inhibited LTA-induced nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells, without affecting cell viability. RGE also inhibited nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) p65 and degradation of $I{\kappa}B-{\alpha}$. In addition, RGE increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and the inhibitory effect of RGE on iNOS expression was abrogated by small interfering RNA-mediated knockdown of HO-1. Moreover, RGE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Furthermore, the phosphoinositide-3-kinase (PI-3K) inhibitor and mitogen-activated protein kinase (MAPK) inhibitors suppressed RGE-mediated expression of HO-1, and RGE enhanced the phosphorylation of Akt, extracellular signal-regulated kinases (ERKs), p38, and c-JUN N-terminal kinases (JNKs). These results suggested that RGE suppressed the production of NO, a proinflammatory mediator, by inducing HO-1 expression via PI-3K/Akt- and MAPK-dependent signaling in LTA-stimulated microglia. The findings indicate that RGE could be used for the treatment of neuroinflammation induced by grampositive bacteria and that it may have therapeutic potential for various neuroinflammation-associated disorders.

Effects of GCP Treatment on the Monosodium Iodoacetate-induced Osteoarthritis in Rats (진교(秦艽)·위령선(威靈仙)·위고초(夏枯草) 복합방이 Monosodium Iodoacetate로 유발된 흰쥐의 골관절염에 미치는 영향)

  • Lee, Seung-Heon;Jeong, Su-Hyeon;Kim, Soon-Joong;Seo, Il-Bok
    • Journal of Korean Medicine Rehabilitation
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    • v.18 no.1
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    • pp.75-94
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    • 2008
  • Objectives : This study was to investigate the effects of GCP treatment on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of Monosodium lodoacetate(0.5mg) into knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of GCP by oraly for same duration. Normal group(n=8) was injected with normal saline and was taken distilled water for 20 days. Body weight was measured at 0, 5, 10, 15, 20 days after injection. Macroscopic examination and histopathological study on articular cartilage of knee joint were operated at 20 days after injection. Proteoglycan(PG) content of articular cartilages of knee joint was represented by safranine O staining, was measured at 20 days injection. Tumor necrosis $factor-{\alpha}$, $Interleukin-1{\beta}$, Interleukin-6 in synovial fluid were measured with ELISA kit at 20 days after injection. Immunohistochemical staining of COX-2, iNOS in knee joints were observed at 20 days after injection. Results : 1. Body weight of the treated group increased compare with control group at 20 days after injection. 2. Macroscopically, degree of osteoarthritis in the treated group were evaluated compared with the control group. 3. PG content in articular cartilage of the treated group was significantly increased compared with the control group. 4. Histopathologically, osteoarthritic scores of the treated group was significantly decreased compared with the control group. 5. $TNF-{\alpha}$ content in synovial fluid of the treated group was decreased compared with the control group. 6. $IL-1{\beta}$ content in synovial fluid of the treated group was significantly decreased compared with the control group. 7. Positive reaction of COX-2 in chondrocytes and synovial membrane of the treated group was faint compared with the control group. Conclusions : On the basis of these results, we concluded that GCP has inhibiting effects on the $IL-1{\beta}$ and COX-2 secretion of chondrocytes and synovial membrane in Monosodium lodoacetate-Induced osteoarthritis model of rats.

Antioxidant and Anti-Inflammatory Activities of Crude Extract and Solvent Fractions of Allium hookeri (삼채의 조추출물과 유기용매 분획물에 대한 항산화 및 항염증 효과)

  • Lee, Yong-Bum;Ham, Young-Min;Yoon, Seon-A;Oh, Dae-Ju;Song, Sang-Mok;Hong, In-Choel;Lee, Si Taek;Hyun, Ho Bong;Kim, Chang-Suk;Yoon, Weon-Jong
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.1
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    • pp.18-25
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    • 2017
  • This study describes the preliminary evaluation of antioxidant and anti-inflammatory activities of Allium hookeri. A. hookeri was extracted using crude extract and then fractionated sequentially with n-hexane, $CH_2Cl_2$, EtOAc, and n-BuOH. To screen for antioxidant and anti-inflammatory agents effectively, we first examined the inhibitory effect of A. hookeri extracts on production of oxidant stresses (2,2-diphenyl-1-picrylhydrazyl, xanthine oxidase, and superoxide). In addition, we examined the inhibitory effects of A. hookeri on production of pro-inflammatory factors (nitric oxide, prostaglandin $E_2$, inducible nitric oxide synthase, and cyclooxygenase-2) in murine macrophage RAW 264.7 cells stimulated with lipopolysaccharide. Of the sequential solvent fractions of A. hookeri, EtOAc fractions showed decreased production of oxidant stresses, and $CH_2Cl_2$ and EtOAc fractions of A. hookeri inhibited production of pro-inflammatory factors. EtOAc fraction inhibited production of pro-inflammatory cytokines (interleukin-6 and -$1{\beta}$). These results suggest that A. hookeri has significant effects on oxidant stresses and pro-inflammatory factors and is a possible antioxidant and anti-inflammatory therapeutic and preventive material.

Suppression Effects of Sopunghwalhyeol-tang(Shufenghuoxie-tang) on the Monosodium Iodoacetate-induced Osteoarthritis in Rats (소풍활혈탕(疎風活血湯)이 Monosodium Iodoacetate로 유발한 흰쥐의 골관절염 억제에 미치는 영향)

  • Kim, Dae-Hyoung;Jeong, Su-Hyeon;Seo, Il-Bok;Kim, Soon-Joong
    • Journal of Korean Medicine Rehabilitation
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    • v.21 no.1
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    • pp.57-77
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    • 2011
  • Objectives : This study was to investigate the suppression effects of Sopunghwalhyeol-tang(Shufenghuoxie-tang) on the monosodium iodoacetate-induced osteoarthritis in rats. Methods : Arthritis was induced by injection of monosodium iodoacetate(0.5 mg) into the both knee joints of rats. Arthritic rats were divided into control(n=8) and treated(n=8) group. Control group was taken distilled water for 20 days. Treated group was taken extracts of Sopunghwalhyeol-tang(Shufenghuoxie-tang) by oraly for same duration. Normal group(n=8) was injected with normal saline and was taken distilled water for 20 days. Macroscopic examination and histopathological study on articular cartilage of knee joint were operated at 20 days after injection. Proteoglycan(PG) content of articular cartilages of knee joint was represented by safranine O staining, was measured at 20 days after injection. Tumor necrosis $factor-{\alpha}(TNF-{\alpha})$, $interleukin-1{\beta}(IL-1{\beta})$, in synovial fluid were measured with enzyme-linked immuno sorbent assay(ELISA) kit at 20 days after injection. Immunohistochemical staining of cyclo-oxygenase-2(COX-2), inducible nitric oxide synthase(iNOS) in knee joints were observed at 20 days after injection. Results : 1. Lymphocytes in peripheral blood the treated group was significantly decreased compared with the control group. 2. PG content in articular cartilage of the treated group was significantly increased compared with the control group. 3. Histopathologically, osteoarthritic scores of the treated group was significantly decreased compared with the control group. 4. $TNF-{\alpha}$ content in synovial fluid of the treated group was significantly decreased compared with the control group. 5. COX-2 revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. 6. Matrix metalloproteinase-3(MMP-3) revelation index in chondrocytes and synovial membrane of the treated group was significantly decreased compared with the control group. Conclusions : On the basis of these results, we concluded that Sopunghwalhyeol-tang(Shufenghuoxie-tang) has inhibiting effects on the $TNF-{\alpha}$, COX-2 and MMP-3 secretion of chondrocytes and synovial membrane in Monosodium Iodoacetate-induced osteoarthritis model of rats.

Anti-inflammatory effect of soil blue-green algae Nostoc commune isolated from Daejeon National Cemetery (국립대전현충원에서 분리한 남조류 구슬말(Nostoc commune)의 항염증 효과)

  • Hong, Hyehyun;Bae, Eun Hee;Park, Tae-Jin;Kang, Min-Sung;Kang, Jae Shin;Chi, Won-Jae;Kim, Seung-Young
    • Journal of Applied Biological Chemistry
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    • v.65 no.2
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    • pp.113-120
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    • 2022
  • We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E2 and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

Elucidation of the profound antagonism of contractile action of phenylephrine in rat aorta effected by an atypical sympathomimetic decongestant

  • Rizvic, Eldina;Jankovic, Goran;Savic, Miroslav M.
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.4
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    • pp.385-395
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    • 2017
  • Vasoconstrictive properties of sympathomimetic drugs are the basis of their widespread use as decongestants and possible source of adverse responses. Insufficiently substantiated practice of combining decongestants in some marketed preparations, such are those containing phenylephrine and lerimazoline, may affect the overall contractile activity, and thus their therapeutic utility. This study aimed to examine the interaction between lerimazoline and phenylephrine in isolated rat aortic rings, and also to assess the substrate of the obtained lerimazoline-induced attenuation of phenylephrine contraction. Namely, while lower concentrations of lerimazoline ($10^{-6}M$ and especially $10^{-7}M$) expectedly tended to potentiate the phenylephrine-induced contractions, lerimazoline in higher concentrations ($10^{-4}M$ and above) unexpectedly and profoundly depleted the phenylephrine concentration-response curve. Suppression of NO with NO synthase (NOS) inhibitor $N^w$-nitro-L-arginine methyl ester (L-NAME; $10^{-4}M$) or NO scavanger $OHB_{12}$ ($10^{-3}M$), as well as non-specific inhibition of $K^+$-channels with tetraethylammonium (TEA; $10^{-3}M$), have reversed lerimazoline-induced relaxation of phenylephrine contractions, while cyclooxygenase inhibitor indomethacin ($10^{-5}M$) did not affect the interaction between two vasoconstrictors. At the receptor level, non-selective 5-HT receptor antagonist methiothepin reversed the attenuating effect of lerimazoline on phenylephrine contraction when applied at $3{\times}10^{-7}$ and $10^{-6}M$, but not at the highest concentration ($10^{-4}M$). Neither the 5-$HT_{1D}$-receptor selective antagonist BRL 15572 ($10^{-6}M$) nor 5-$HT_7$ receptor selective antagonist SB 269970 ($10^{-6}M$) affected the lerimazoline-induced attenuation of phenylephrine activity. The mechanism of lerimazoline-induced suppression of phenylephrine contractions may involve potentiation of activity of NO and $K^+$-channels and activation of some methiothepin-sensitive receptors, possibly of the 5-$HT_{2B}$ subtype.

Task-Specific Hazardous Chemicals Used by Nail Shop Technicians (네일 샵 종사자들의 직무 형태별 취급 유해화학물질)

  • Choi, Sangjun;Park, Sung-Ae;Yoon, Chungsik;Kim, Sunju
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.25 no.4
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    • pp.446-464
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    • 2015
  • Objectives: This study was conducted to evaluate the task-specific hazards of chemicals used by nail technicians in Daegu Metropolitan City. Materials: A total of 30 nail shops located in Daegu City were surveyed to investigate the major tasks and practices performed by nail technicians and the ingredients listed in nail care products used in shops. We also collected instructions for use and material safety data sheets(MSDSs) of nail care products and compared CAS Nos. of ingredients with the lists of chemicals regulated by the Industrial Safety and Health Act(ISHA) and Chemical Substances Control Act(CSCA). Results: A total of 125 chemical ingredients were found in 468 nail care products used at the 30 nail shops. The most frequently found ingredients were ethyl acetate(72%), followed by n-butyl acetate(71.8%), isopropanol(56%), benzophenone(51.1%), nitrocellulose(46.4%) and ethanol(45.3%). Comparing six tasks, the task of manicuring used the most products at 222 products containing 91 ingredients. Among the 125 ingredients, there are 31 chemicals with occupational exposure limits(OEL) designated by the Ministry of Employment and Labor(MoEL), eight categorized as carcinogens, one mutagen and two reproductive toxic chemicals. In terms of carcinogens, formaldehyde was identified as the only confirmed human carcinogen(1A). We found that there was one chemical with a permissible limit, one special management substance, 18 workplace monitoring substances and ten special health diagnosis substances regulated by ISHA. For CSCA, nine poisonous substances, six substances requiring preparation for accidents and one restricted substance were identified. Conclusions: Based on these findings, formaldehyde was identified as one of the chemicals that should most strictly be controlled for the protection of the health of nail technicians and customers. At the same time, it is necessary to distribute materials with detailed hazardous information of nail care products for nail shop technicians.

Views on the Orientation of Science in Decision-Making Revealed in Undergraduate Students' Discussion on Socio-Scientific Issues

  • Jho, Hunkoog;Song, Jinwoong;Levinson, Ralph
    • Journal of The Korean Association For Science Education
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    • v.33 no.3
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    • pp.581-596
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    • 2013
  • The aim of this study was to identify students' views on the orientation of science and to investigate the relationship between their views and decision-making on socio-scientific issues (SSI). In this study, 27 university students attending a science course were asked to discuss four controversial issues: the Toyota recall, the green car, the global warming and swine influenza (influenza A (H1N1)). The study was comprised of two stages. At the first stage, we examined students' views on the nature of science and on the orientation of science with the open-ended questionnaire based on VNOS and VOSTS. While they held relatively similar views on the nature of science, their views on the orientation of science were distinct as pragmatic, intrinsic, communal and ethical views. At the second stage, to examine the role of their views on the orientation of science in decision-making, we selected four students who had similar views on NOS but different views on the orientation of science. The four students were selected from each group of views on the orientation of science and their decision-making processes were analyzed following grounded theory. Across SSIs, they relied upon their views on the orientation of science as the strategies for decision, though considered different perception, and causal and contextual conditions. This study indicates that understanding students' views on the orientation of science would be helpful for achieving scientific literacy for informed decision.

Extracelluar Signal-Regulated Kinase-Dependent Nitric Oxide Production from Macrophage-Like Cells by Lactic Acid Bacteria

  • Byeon, Se-Eun;Yoo, Dae-Sung;Lee, Jae-Hwi;Kim, Suk;Rhee, Man-Hee;Park, Hwa-Jin;Cho, Jae-Youl
    • Biomolecules & Therapeutics
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    • v.17 no.3
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    • pp.276-281
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    • 2009
  • Lactic acid bacteria (LAB) are considered as probiotics with immunostimulatory property. In this study, we investigated the molecular mechanism of its immunostimulating potency on macrophages using combined preparation of LAB (cpLAB). cpLAB is able to strongly stimulate nitric oxide (NO) production as well as inducible NO synthase (iNOS) expression from macrophage-like RAW264.7 cells. The cpLAB-induced NO release seemed to be mediated by extracellular signal-regulated kinase (ERK) but not p38 and C-Jun N-terminal kinase (JNK), since U0126, an ERK inhibitor, clearly suppressed NO production. cpLAB significantly diminished the binding of toll like receptor (TLR)-2 antibody up to 25%, implying that cpLAB-mediated activation of macrophages may be required for the functional activation of TLR-2, but not TLR-4. Therefore, our data suggest that cpLAB may directly allow macrophages to immunostimulating potency via activation of TLR-2 and ERK.