• Title/Summary/Keyword: Inducible nitric oxide

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The Role of Nitric Oxide in Mycobacterial Infections

  • Yang, Chul-Su;Yuk, Jae-Min;Jo, Eun-Kyeong
    • IMMUNE NETWORK
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    • v.9 no.2
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    • pp.46-52
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    • 2009
  • Although tuberculosis poses a significant health threat to the global population, it is a challenge to develop new and effective therapeutic strategies. Nitric oxide (NO) and inducible NO synthase (iNOS) are important in innate immune responses to various intracellular bacterial infections, including mycobacterial infections. It is generally recognized that reactive nitrogen intermediates play an effective role in host defense mechanisms against tuberculosis. In a murine model of tuberculosis, NO plays a crucial role in antimycobacterial activity; however, it is controversial whether NO is critically involved in host defense against Mycobacterium tuberculosis in humans. Here, we review the roles of NO in host defense against murine and human tuberculosis. We also discuss the specific roles of NO in the central nervous system and lung epithelial cells during mycobacterial infection. A greater understanding of these defense mechanisms in human tuberculosis will aid in the development of new strategies for the treatment of disease.

Leaves of Raphanus sativus L. Shows Anti-Inflammatory Activity in LPS-Stimulated Macrophages via Suppression of COX-2 and iNOS Expression.

  • Park, Hye-Jin;Song, Minjung
    • Preventive Nutrition and Food Science
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    • v.22 no.1
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    • pp.50-55
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    • 2017
  • Raphanus sativus L. (RS) is a cruciferous vegetable that is widely consumed in Korea. The anticancer activity of leaves of RS (RSL) extract has been investigated; however, no studies focused on its anti-inflammatory effects. Therefore, the aim of the current study was to evaluate the anti-inflammatory effects of RSL extract. In brief, RSL powder was fractionated into n-hexane, chloroform, ethyl acetate, n-butanol, and water-soluble fractions. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells were treated with each fraction for initial screening. It was found that the chloroform fraction significantly inhibited nitric oxide release in LPS-stimulated RAW264.7 cells with a half maximal inhibitory concentration value of $196{\mu}g/mL$. In addition, the mRNA and protein expression levels of inducible nitric oxide synthase, measured using reverse transcriptase-polymerase chain reaction and western blotting, respectively, were reduced in a concentration-dependent manner. Moreover, the inflammatory cyclooxygenase-2 enzyme expression decreased. Furthermore, the expression of nuclear factor-kappa B ($NF-{\kappa}B$), the key regulator of the transcriptional activation of the inflammatory cytokine genes, was reduced by the RSL chloroform fraction. Therefore, the results of our study suggest that RSL exhibits anti-inflammatory effects in LPS-stimulated macrophages via $NF-{\kappa}B$ inactivation.

Panax notoginseng inhibits LPS-induced pro-inflammatory mediators in microglia (삼칠근(三七根)의 LPS에 의해 활성화된 뇌신경교세포(腦神經膠細胞)로부터의 염증매개물질(炎症媒介物質) 생성억제효과(生成抑制效果))

  • Jung, Hyo-Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.21 no.4
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    • pp.93-101
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    • 2006
  • Objectives : Increasing evidence has linked chronic inflammation to a number of neurodegenerative disorders including Alzheimer's disease(AD), Parkinson's disease(PD) and Huntington's disease(HD) in the inflammatory process. Uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines ($TNF-{\alpha}$, $IL-1{\beta}$ and IL-6), NO, PEG2 and superoxide. In this study, the immunomodulatory effects of the herbal extract Panax notoginseng on cultured BV2 microglial cells and primary microglia were investigated to address potential therapeutic or toxic effects. Notoginseng radix extracts extracted from the root of the plant using Methanol. Methods : Cells were stimulated with LPS and treated with notoginseng at different concentrations. Results : Notoginseng significantly decreased LPS-induced production of $TNF-{\alpha}$ and IL-6 by the cultured microglial cells in a dose-dependent manner. The activation of iNOS mRNA and secretion of nitric oxide(NO) in microglial cells were inhibited in microglial cells in a dose-dependent manner by notoginseng. Conclusion : These results indicate that notoginseng inhibits LPS-induced activation of microglial cells and demonstrates notoginseng possess anti-inflammatory and immunosuppressive properties in vitro.

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High molecular weight water-soluble chitosan acts as an accelerator of macrophages activation by recombinant interferon ${\gamma}$ via a process involving $_L$-arginine -dependent nitric oxide production

  • Kim, Hyung-Min
    • Advances in Traditional Medicine
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    • v.1 no.1
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    • pp.71-81
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    • 2000
  • High molecular weight water-insoluble chitosan alone has been previously shown to exhibit in vitro stimulatory effect on macrophages nitric oxide (NO) production. However, high molecular weight water-soluble chitosan (WSC) had no effect on NO production by itself. When WSC was used in combination with recombinant $interferon-{\gamma}\;(Rifn-{\gamma})$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of WSC on NO synthesis was shown at 24 h after treatment with $rIFN-{\gamma}$. The increased production of NO from $rIFN-{\gamma}$ plus WSC-stimulated RAW 264.7 macrophages was decreased by the treatment with $N^G$ $monomethyl-_L-arginine$. The increase in NO synthesis was reflected, as an increased amounts of inducible NO synthase (iNOS) protein. Synergy between $rIFN-{\gamma}$ and WSC was mainly dependent on WSC-induced nuclear $factor-_KB$ activation. The present results indicate that WSC may provide various activities such as anti-microbial, anti-tumoral, and anti-viral. In addition, since NO has emerged as an important intracellular and intercellular regulatory molecule having functions as diverse as vasodilation, neural communication, cell growth regulation and host defense, it is tempting to hypothesize that this WSC is involved in the local control of the various fundamental processes such as cardiagra, cardiac infarction, impotence etc.

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Anti-inflammatory effect of various solvent extract from Atractylodes japonica on Lipopolysaccharide-induced Inflammation in BV2 cells. (창출 추출물의 BV2 cell 소염작용에 관한 실험적 연구)

  • Hur, Inn-Hee;Sim, Sung-Yong;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.2 s.33
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    • pp.36-46
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    • 2007
  • Objective : In this study, the effect of Atractylodes japonica against LPS induced inflammation in mouse microglia BV2 cells was investigated. Method : Microglia BV2 Cells viability was determined using the MTT assay. We used water, ethanol extract from Atractylodes japonica and studied on the anti-inflammatory effect of lipopolysaccharide-induced inflammation using reverse transcription polymerase chain reaction (RT-PCR), western blot, and nitric oxide detection on mouse microglia BV2 cells. Result : The MTT assay revealed that it's extract has no significant cytotoxicity in the microglia BV2 cell. Various solvent extract from Atractylodes japonica inhibited nitrite production, iNOS protein and mRNA expression levels. And also it's extracts significantly reduced lipopolysaccharide-induced COX-2 activation in RT-PCR and western blot in lipopolysaccharide-induced microglia BV2 cells Conclusion : In this study, it's extracts was shown to suppress NO production by inhibiting iNOS expression and COX-2 activity. With this effects of anti-inflammation, we suggests that, it's extracts may be a useful candidate for the development of a drug on the related inflammatory diseases in brain.

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Ethanol extract of Synurus deltoides (Aiton) Nakai suppresses in vitro LPS-induced cytokine production in RAW 264.7 macrophages and in vivo acute inflammatory symptoms

  • Jiang, Yunyao;Wang, Myeong-Hyeon
    • Nutrition Research and Practice
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    • v.8 no.1
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    • pp.11-19
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    • 2014
  • Synurus deltoides (Aiton) Nakai, belonging to the Compositae family, is an edible plant widely distributed in Northeast Asia. In this study, we examined the mechanisms underlying the immunomodulative effects of the ethanol extract of S. deltoides (SDE). The SDE extract strongly down-regulated the mRNA expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor (TNF)-${\alpha}$, thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and TNF-${\alpha}$ in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, SDE also suppressed the nuclear translocation of the activation protein (AP)-1 and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and simultaneously decreased the phosphorylation of extracellular signal-regulated protein kinases (ERK), p38, and Akt. In agreement with the in vitro observations, the orally administered SDE ameliorated the acute inflammatory symptoms in the arachidonic acid-induced ear edema and the EtOH/HCl-induced gastritis in mice. Therefore, S. deltoides have a potential anti-inflammatory capacity in vitro and in vivo, suggesting the potential therapeutic use in the inflammation-associated disorders.

Anti-inflammatory effects of porcine placenta in forced swimming tested fatigue mice and RAW264.7 cells

  • Nam, Sun-Young;Kang, Sang Woo;Kim, Jongbae;Lee, Won Kyung
    • CELLMED
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    • v.7 no.4
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    • pp.20.1-20.6
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    • 2017
  • Inflammation has been linked to various diseases. Especially, fatigue is a frequent symptom in several inflammatory disorders. Therefore, blocking inflammatory process is effective in fatigue. We investigated whether Denmark porcine placenta (DPP) alleviates fatigue by inhibiting inflammatory reaction using forced swimming test (FST) animal model and RAW264.7 cells. In FST-induced fatigue animal model, the mice which received the DPP for 21 days showed decreases of interleukin $(IL)-1{\beta}$ and IL-6 serum levels. Furthermore, our data revealed that lipopolysaccharide (LPS)-induced $IL-1{\beta}$, IL-6, and tumor necrosis $factor-{\alpha}$ secretion were markedly inhibited by DPP in RAW264.7 cells without inducing cytotoxicity. LPS-enhanced nitric oxide secretion and inducible nitric oxide synthase expression were inhibited by DPP. The present study also figured out that these effects of DPP were mediated by blockade of caspase-1 and nuclear $factor-{\kappa}B$ activation. Taken together, our results indicated that DPP could be alleviating fatigue as candidate of anti-inflammatory agent.

Nitric Oxide Synthase Expressions in ADR-induced Cardiomyopathy in Rats

  • Liu, Baogang;Li, Hongli;Qu, Hongyan;Sun, Baogui
    • BMB Reports
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    • v.39 no.6
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    • pp.759-765
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    • 2006
  • In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADR-treated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.

Tribulus terrestris Suppresses the Lipopolysaccharide-Induced Inflammatory Reaction in RAW264.7 Macrophages through Heme Oxygenase-1 Expressions

  • Kim, Jai Eun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.1
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    • pp.63-68
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    • 2014
  • The fruit of Tribulus terrestris L. (Zygophyllaceae) is an important source of traditional Korean and Chinese medicines. In this study, NNMBS223, consisting of the ethanol extract of T. terrestris, showed potent anti-inflammatory activities in RAW264.7 macrophages. We investigated the effect of NNMBS223 in suppressing the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and production of iNOS-derived nitric oxide (NO), COX-2-derived prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-stimulated macrophages. In addition, NNMBS223 induced expression of heme oxygenase (HO)-1 through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) in macrophages. The effects of NNMBS223 on LPS-induced production of NO and PGE2 were partially reversed by the HO activity inhibitor tin protoporphyrin (SnPP). These findings suggest that Nrf2-dependent increases in expression of HO-1 induced by NNMBS223 conferred anti-inflammatory activities in LPS stimulated RAW264.7 macrophages.

Antioxidant and Anti-Nociceptive Activities of Ulmus davidiana var. japonica

  • Jung, Hyun-Joo;Kang, Hyun-Jung;Song, Yun-Seon;Lim, Chang-Jin;Park, Eun-Hee
    • Biomolecules & Therapeutics
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    • v.16 no.1
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    • pp.9-13
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    • 2008
  • Some pharmacological activities of Ulmus davidiana var. japonica were evaluated using its methanol extract (UDE). An acute anti-inflammatory activity of UDE was assessed using carrageenan-induced hind paw edema in rats. UDE exhibited an antioxidant activity when assayed by a stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). Dose-dependent anti-nociceptive activity of UDE was assessed using the acetic acid-induced writhing test in mice. UDE was able to diminish the reactive oxygen species (ROS) level in the lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. UDE also suppressed production of nitric oxide and induction of inducible nitric oxide synthase and cyclooxygenase-2 in the stimulated macrophages cells. collectively, the results imply that U. davidiana var. japonica has antioxidant and anti-nociceptive activities in addition to anti-inflammatory activity.