• Title/Summary/Keyword: Inducible NO synthase

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NF-kB and AP-1-regulatory Mechanism of Buthus Martensi Karsch Herbal Acupuncture Solution on Inflammatory Cytokine-induced Human Chondrocytes Dysfunction

  • Cho, Jae-Yong;Kim, Kyung-Ho;Cho, Hyun-Seok;Lim, Dae-Jung;Hwang, Ji-Hye;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.23 no.2
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    • pp.61-72
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    • 2006
  • Objectives : Human chondrocytes co-treated with Buthus martensi Karsch herbal acupuncture solution(BMK-HAS) extract produced significantly less NO compared with chondrocytes stimulated with $IL-1{\beta}$ alone Methods : Activation and translocation of and NF-kB DNA binding activity were determined by Western blotting and specific enzyme-linked immunosorbent assay. Results : The inhibition of NO production correlated with the suppression of induction and expression of nuclear factor-kB (NF-kB) and activation protein-1 (AP-1)-dependent gene. BMK-HAS inhibited the activation and translocation of NF-kB to the nucleus, indicating that BMK-HAS inhibits the $IL-1{\beta}-induced$ production of NO in human chondrocytes by interfering with the activation of NF-kB through a novel mechanism. In addition, BMK-HAS reduced prostaglandin E2 (PGE2)production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) or cyclooxygenase-1 (COX-1) was observed. My data, therefore, suggest that BMK-HAS may be a therapeutically effective inhibitor of $IL-1{\beta}-induced$ inflammatory effects that are dependent on NF-kB activation in human OA chondrocytes. Conclusion : The results indicate that BMK-HAS exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and PGE2 production, which could be due to a decreased expression of iNOS and COX-2 through the transcription factors NF-kB and AP-1.

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Lonicera Japonioa Inhibits the Production of NO through the Suppression of NF-kB Activity in LPS-stimulated Mouse Peritoneal Macrophages

  • Kim Young-hee;Kim Han-do
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.17 no.1
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    • pp.163-171
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    • 2004
  • The flowers of Lonicera japonica Thunb. (Caprifoliaceae) has been used as anti-inflammatory drug in the folk medicine recipe and been proved its anti-inflammatory effect in the oriental medicine. However, the action mechanism of Lonicera japonica that exhibits anti-inflammatory effects has not been determined. Since nitric oxide (NO) is one of the major inflammatory parameter, we studied the effect of aqueous extracts of Lonicera japonica (AELJ) on NO production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. NO and inducible NO synthase (iNOS) level were significantly reduced in LPS-stimulated macrophages by AELJ compared to those without Electrophoretic mobility shift assay (EMSA) indicated that AELJ blocked the activation of nuclear factor kappa B (NF-kB), which was considered to be a potential transcription factor for the iNOS expression. AELJ also blocked the phosphorylation and degradation of inhibitor of kappa B-alpha (IkB-${\alpha}$). Furthermore, IkB kinase alpha (IKK${\alpha}$), which is known to phosphorylate serine residues of IkB directly, is inhibited by AELJ in vivo and in vitro. These results suggest that AELJ could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of NF-kB activity.

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15-Deoxy-Δ12,14-Prostaglandin J2 Protects Against Nitrosative Pc12 Cell Death Through Up-Regulation of Intracellular Glutathione Level

  • Lim, So-Young;Jang, Jung-Hee;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.189-189
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    • 2003
  • Recent studies suggest that inflammatory events are implicated in a variety of human diseases including cancer and neurodegenerative diseases. It has been reported that expression of inducible cyclooxygenase (COX) and nitric oxide (NO) synthase and subsequent production of prostaglandins (PG)s and NO, respectively are elevated in many inflammatory disorders.(omitted)

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Induction of Inos Gene Expression by Polysaccharide Isolated from Poria Cocos Sclerotium

  • Jeon, Young-Jin
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.164-164
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    • 2003
  • We show that PCSC, a polysaccharide isolated from the sclerotium of Poria cocos with one percent sodium carbonate, significantly induces nitric oxide (NO) production and inducible NO synthase (iNOS) transcription through the activation of nuclear factor-$\kappa$B/Rel (NF-$\kappa$B/Rel).(omitted)

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Scrophularia Buergeriana inhibits the Production of NO through the Suppression of NF-kB adivity in LPS-stimulated Mouse Peritoneal Macrophages

  • Ha Mi Suk;Kim Young Hee;Ko Woo Shin;Kim Han Do
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.6
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    • pp.1284-1290
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    • 2002
  • Scrophularia buergeriana Miquel (Scrophulariaceae) has been used as an anti-inflammatory drug in the folk medicine recipe and been proved its anti-inflammatory effect in the oriental medicine. Since nitric oxide (NO) and superoxide anion (O/sub 2//sup -/) are ones of the major inflammatory parameters, we studied the effect of aqueous extracts of Scrophularia buergeriana (SB) on NO and O/sub 2//sup -/ production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. NO, O/sub 2//sup -/production and inducible NO synthase (iNOS) level were significantly reduced in LPS-activated macrophages by SB compared to those without. Electrophoretic mobility shift assay (EMSA) indicated that SB blocked the activation of NF-kB, which was considered to be a potential transcription factor for the iNOS expression. SB also blocked degradation of IkBα. Furthermore, IkB kinase alpha (IKKα), which phosphorylates serine residues of IkB directly, is inhibited by SB. These results suggest that SB could exert its anti-inflammatory actions by suppressing the activation of NF-kB through inhibition of IKK activity.

Ovalbumin Hydrolysates Inhibit Nitric Oxide Production in LPS-induced RAW 264.7 Macrophages

  • Kim, Hyun Suk;Lee, Jae Hoon;Moon, Sun Hee;Ahn, Dong Uk;Paik, Hyun-Dong
    • Food Science of Animal Resources
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    • v.40 no.2
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    • pp.274-285
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    • 2020
  • In this study, ovalbumin (OVA) hydrolysates were prepared using various proteolytic enzymes and the anti-inflammatory activities of the hydrolysates were determined. Also, the potential application of OVA as a functional food material was discussed. The effect of OVA hydrolysates on the inhibition of nitric oxide (NO) production was evaluated via the Griess reaction, and their effects on the expression of inducible NO synthase (inducible nitric oxide synthase, iNOS) were assessed using the quantitative real-time PCR and Western blotting. To determine the mechanism by which OVA hydrolysates activate macrophages, pathways associated with the mitogen-activated protein kinase (MAPK) signaling were evaluated. When the OVA hydrolysates were added to RAW 264.7 cells without lipopolysaccharide (LPS) stimulation, they did not affect the production of NO. However, both the OVA-Protex 6L hydrolysate (OHPT) and OVA-trypsin hydrolysate (OHT) inhibited NO production dose-dependently in LPS-stimulated RAW 264.7 cells. Especially, OHT showed a strong NO-inhibitory activity (62.35% at 2 mg/mL) and suppressed iNOS production and the mRNA expression for iNOS (p<0.05). Also, OHT treatment decreased the phosphorylation levels of Jun amino-terminal kinases (JNK) and extracellular signal-regulated kinases (ERK) in the MAPK signaling pathway. These findings suggested that OVA hydrolysates could be used as an anti-inflammatory agent that prevent the overproduction of NO.

N-nitroso-N-methylurea and N-nitroso-N-ethylurea Decrease in Nitric Oxide Production in Human Malignant Keratinocytes

  • Moon, Ki-Young
    • Biomedical Science Letters
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    • v.24 no.1
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    • pp.50-54
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    • 2018
  • N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), direct alkylating chemical mutagens and carcinogens, are shown to be the upregulators of cellular $NF-{\kappa}B$, regulating various genes that mediate tumorigenesis and carcinogenesis. Nitric oxide (NO), a toxic reactive radical gas, has been known to induce programmed cell death or apoptosis in various cells. Therefore, the assessment of NO production was examined to elucidate the possible contribution of NO release to the chemical carcinogenic potency of NMU and NEU in human skin cells. NMU and NEU did not alter the NO production, but they caused a significant downregulation of the NO generation on lipopolysaccharide (LPS)-induced NO production at concentrations ranging from $2{\sim}5{\mu}M$. The degree of downregulation of NO by NMU and NEU decreased up to 15% and 20%, respectively, compared to the control. These results demonstrate that the LPS-inducible keratinocytes NO synthase is involved in modulating carcinogenic potency by NMU and NEU, and the regulation of the cellular $NF-{\kappa}B$ activity by NMU and NEU is negatively correlated with the level of LPS-induced NO production in human skin cells. The findings of this study suggest the hypothesis that NMU and NEU-induced carcinogenesis may be associated with the downregulation of NO production, and the inducible NO may play an important role in NMU and NEU-induced carcinogenicity in human epidermal keratinocytes.

Xanthorrhizol inhibits pro-inflammatory mediators in mouse macrophage cells

  • Min, Hye-Young;Park, Hyen-Joo;Park, Eun-Jung;Park, Kwang-Kyun;Chung, Won-Yoon;Hwang, Jae-Kwan;Lee, Sang-Kook
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.378.1-378.1
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    • 2002
  • Prostaglandins (PGs) and nitric oxide (NO) are essential to maintain homeostasis and defensa systems in human beings. However. overproduced PGs and NO by inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS), respectively. cause tissue damages. chronic inflammation. and carcinogenesis. In this view. the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory or cancer chemopreventive agents. (omitted)

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Inhibition of nitric oxide and TNF-$\alpha$ production by propenone compound through blockaded of NF-$\kappa$B activation in cultured murine macrophages

  • Ju, Hye-Kyung;Lee, Eun-Kyung;Jahng, Yurng-Dong;Lee, Eung-Seok;Chang, Hyeun-Wook
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.156.2-157
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    • 2003
  • Lipopolysaccharide (LPS)-stimulated macrophages produced a large amounts of nitric oxide (NO) by inducible nitric oxide synthase (iNOS). This is an important mechanism in macrophages-induced septic shock and inflammation. In the present study, we tested a synthetic propenone compound, l-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) for its ability to inhibit the production of tumor necrosis factor-a (TNF-$\alpha$) and an inducible enzyme, iNOS, in the LPS-stimulated murine macrophage-like cell line, Raw264.7. FPP-3 consistently inhibited nitric oxide (NO) and TNF-$\alpha$ production in a dose dependent manner, with $IC_50$> values of 10.0 and 13.1 $\mu$M, respectively. (omitted)

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Inhibition of an Inducible Nitric Oxide Synthase Expression by a Hexane Extract from Perilla frutescens cv. Chookyoupjaso Mutant Induced by Mutagenesis with Gamma-ray (방사선 유도 돌연변이 약용들깨 핵산 추출물의 Inducible Nitric Oxide Synthase 저해활성)

  • Park, Yong Dae;Kang, Min Ah;Lee, Hyo Jung;Jin, Chang Hyun;Choi, Dae Seong;Kim, Dong Sub;Kang, Si-Yong;Byun, Myung Woo;Jeong, Il Yun
    • Journal of Radiation Industry
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    • v.3 no.1
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    • pp.13-18
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    • 2009
  • In earlier investigations, seeds of Perilla frutescens(L.) Britt. cv. Chookyoupjaso were irradiated with 200 Gy gamma ray to generate mutagenesis. The aim of this study is to investigate the effects of a hexane extract from Perilla frutescens (L.) Britt. cv. Chookyoupjaso mutant 45 on the actions of anti-inflammatory activity on inducible nitric oxide synthase, and an identification of the major active compound. The hexane extract from P. frutescens exhibited activity of inhibition of a NO production ($IC_{50}$, $295.1{\mu}g\;ml^{-1}$). The hexane extract was further divided into subfractions by silica-gel chromatogarphy. Inhibition of the NO production by various fractions was assayed in LPS-stimulated RAW 264.7 cells. Among the seven fractions, the 5th fraction was the most effective ($IC_{50}$, $19.5{\mu}g\;ml^{-1}$). The 5th fraction suppressed the expression of protein of iNOS in LPS-induced RAW 264.7 cells, and GC/MS analyses showed that isoegomaketone is a major bio-active compound in the 5th fraction. The result indicated that isoegomaketone has a good potential to be developed as an anti-inflammation agent.