• Title/Summary/Keyword: Inducible nitric oxide

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Antioxidant and Suppressive Effects of Ethanolic Extract Fractions from Safflower (Carthamus tinctorius L.) Flower on the Biosynthesis of Inflammatory Mediators from LPS-stimulated RAW 264.7 Cells

  • Lee, Je-Hyuk;Jeon, Choon-Sik;Kim, Gun-Hee
    • Food Science and Biotechnology
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    • v.18 no.1
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    • pp.143-149
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    • 2009
  • The aim of this study was to elucidate the anti-inflammatory activity of safflower (Carthamus tinctorius L.) ethanolic extract fractions (CFEFs). Butanol fraction had the strongest antioxidant activity, and all CFEFs, except for chloroform fraction, partly inhibited lipopolysaccharide (LPS)-induced nitrite production in RAW 264.7 cells. In the cell-free system, hexane and butanol fractions chemically quenched nitric oxide (NO). In addition, the iNOS mRNA transcription was suppressed by ethanol extract and hexane fraction in LPS-stimulated RAW 264.7 cells. Taken together, the inhibitory effect of CFEFs on NO production from LPS-stimulated RAW 264.7 cells, might be due to both the chemical NO quenching activity and the suppression of iNOS mRNA transcription partially. The synthesis of prostaglandin $E_2$ ($PGE_2$) was potently inhibited by ethanol extract to below basal label, and the transcription of cyclooxygenase-2 (COX-2), an enzyme involving in $PGE_2$ synthesis, was partially suppressed by ethanol extract and hexane fraction. Based on these results, CFEFs may be useful as an alternative medicine for the relief and retardation of immunological inflammatory responses through the reduction of inflammatory mediators, including NO and $PGE_2$ production.

Flavonoids Differentially Modulate Nitric Oxide Production Pathways in Lipopolysaccharide-Activated RAW264.7 Cells

  • Kim Ae Ra;Cho Jae Youl;Zou Yani;Choi Jae Sue;Chung Hae Young
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.297-304
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    • 2005
  • Naturally occurring flavonoids are known to modulate various inflammatory and immune processes. Based on structural property, in this study, molecular mechanism of flavonoids in modulating nitric oxide (NO) production and its signaling pathway were investigated using lipopolysaccharide (LPS)-activated RAW264.7 cells. Although flavonol-typed flavonoids (kaempferol and quercetin) more potently scavenged reactivity of nitric oxide ($\cdot$NO) as well as peroxynitrite (ONOO$\kappa$) than isoflavones (genistein and genistin), kaempferol, quercetin and genistein showed a little difference in inhibition of both inducible NO synthase expression and NO production, with IC$_{50}$ values of 13.9, 20.1 and 26.8 $\mu$M. However, there was a striking pattern related to structural feature in modulation of LPS-mediated signaling pathways. Thus, flavonols only inhibited transcription factor AP-1 activation, whereas isoflavones suppressed the DNA binding activation of NF-$\kappa$B and C/EBP$\beta$. Therefore, these data suggest that structural feature may be linked to decide drugs target molecule in LPS-mediated signaling pathways, rather than its potency.

Biphasic Effects of Nitric Oxide in Liver Toxicity (간장독성에서 니트릭 옥시드의 양면적 효과)

  • Park, Chang-Won;Cho, Dae-Hyun;Hong, Sung-Youl;Han, Jeung-Whan;Lee, Hyang-Woo
    • YAKHAK HOEJI
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    • v.42 no.6
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    • pp.598-606
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    • 1998
  • The liver expresses a considerable amount of nitric oxide (NO) upon induction with cytokines or/and endotoxin. The NO synthesized by inducible NO synthase (NOS) of the liver see ms to play a role in various hepatic physiological processes. Here we investigate the effects of NO on acetaminophen (AA)-induced liver injury. The treatment of S-nitros-N-acetyl penicillamine (SNAP, exogenous NO donor) at the dose of 0.1mM decreased AA-induced hepatotoxicity suggesting the possibility of NO to play a role in protection from the hepatotoxicity induced by AA. On the other hand, the excessive NO produced by NO donor (SNAP: 0.5, 2.5, 6.25mM) has been shown to cause a concentration dependent hepatotoxicity, and such damages was decreased by Superoxide and increased by superoxide dismutase, indicating that the hepatotoxicity induced by excessive NO depends on balancing between NO and superoxide. Taken together, the results indicate that NO has biphasic effects on hepatotoxicity.

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Anti-inflammatory Properties of Meso-dihydroguaiaretic Acid in Lipopolysaccharide-induced Macrophage

  • Kim, Yong-Jae;Kang, Yeo-Jin;Kim, Tack-Joong
    • Biomedical Science Letters
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    • v.16 no.2
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    • pp.91-95
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    • 2010
  • Meso-dihydroguaiaretic acid (MDGA) is a medicinal herbal product isolated from the bark of Machilus thunbergii Sieb. et Zucc. (Lauraceae). It exhibits a neuroprotective effect and also exerts cytotoxicity to certain cancer cells. In the present study, we investigated whether or not MDGA inhibits inflammatory reaction through the inhibition of nitric oxide (NO) generation. The results showed that MDGA (5~$25 {\mu}M$) inhibited 100 ng/ml lipopolysaccharide (LPS)- induced NO generation in macrophage Raw 264.7 cells in a concentration-dependent manner. We also measured the cytotoxic effects of MDGA on Raw 264.7 cells and found no evidence of cytotoxicity. The inhibition of NO generation by MDGA was consistent with the inhibitory effect on the expression of inducible nitric oxide synthase (iNOS). In addition, MDGA inhibited the LPS-induced gene expression of $interleukin-1{\beta}$ $(IL-1{\beta})$ as well as tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$. The present results may provide that MDGA has anti-inflammatory properties through inhibition of the toll-like receptors (TLRs) pathway, and suggest that MDGA can be used as an anti-inflammatory agent.

Ginsenosides-mediated Vascular Relaxation and Its Molecular Mechanisms (진세노사이드의 혈관확장작용과 분자기전)

  • Kim, Nak-Doo
    • Journal of Ginseng Research
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    • v.32 no.2
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    • pp.89-98
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    • 2008
  • There are increasing evidences in the literatures on the potential role of ginsenosides in treating cardiovascular diseases. In this article, current information about ginsenosides-mediated vascular relaxation are reviewed. From the published studies using isolated organs, cell culture systems and animal models, ginsenosides are shown to relax blood vessels and improve blood flow through diverse mechanisms, including nitric oxide release by activating eNOS phosphorylation via PI3K/Akt and/or ERK1/2 pathways in endothelial cells, induction of inducible nitric oxide synthase through activation of NF-${\kappa}$B, reducing the intracelluar Ca$^{2+}$ levels by activating Ca$^{2+}$-activated K$^{+}$ channels in vascular smooth muscle cells and reducing platelet aggregation by decreasing thromboxane A$_2$ formation and intracelluar Ca$^{2+}$in platelets. In addition, the relevant clinical trials regarding the effects of ginsenosides on the cardiovascular disease are summarized, particulary focusing on managing hypertension and improving thrombotic disorders. Finally, antagonistic effects of ginsenosides on the prostaglandin H$_2$ receptor and scavenging effects on the generation of oxygen-derived free radicals in spontaneously hypertensive rats (SHR) are discussed.

Anti-inflammatory activity of methanol extract isolated from stem bark of Albizia julibrissin

  • Na, Ho-Jeong;Cha, Dong-Seok;Jeon, Hoon
    • Advances in Traditional Medicine
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    • v.9 no.2
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    • pp.157-163
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    • 2009
  • Albizia julibrissin (AJ) has been used widely as a traditional medicine. In macrophages nitric oxide (NO) is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions including inflammation and carcinogenesis. In this study we have examined the NO inhibition effect of 85% methanol extracts of AJ in mouse macrophage. Lipopolysaccharide (LPS) has been reported to induce production of NO. Extracts of AJ (1, 10, $100{\mu}g/ml$) suppressed nitric oxide production in LPS-stimulated ($100{\mu}g/ml$) mouse (C57BL/6) macrophages and analyzed by ELISA. In addition, it also attenuated the expression of inflammatory products like Interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and inducible NOS (iNOS) as assessed by immunoblotting with specific antibodies. These results suggest that 85% methanol extracts of AJ would be useful in inflammatory diseases.

Anti-Inflammatory Effect of Extracts from Ligustrum obtusifolium S. fruits in RAW 264.7 Macrophages (RAW 264.7 대식세포 내에서 남정목 열매 추출물의 항염증 효과)

  • Moon, Ju-Ho;Go, Heung;Shin, Seon-Mi;Kim, Ki-Tae
    • The Journal of the Society of Korean Medicine Diagnostics
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    • v.17 no.3
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    • pp.263-273
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    • 2013
  • Objectives This study was designed to investigate the anti-inflammatory effect of extracts from Ligustrum obtusifolium S. fruits(LOF) in RAW 264.7 Macrophages stimulated with lipopolysaccharide(LPS). Methods We examined productions of nitric oxide(NO), reactive oxygen species(ROS), inducible isoforms of NO synthase(iNOS), cyclooxygenase-2(COX-2) to investigate the anti-inflammatory effect of LOF extracts. In addition, we measured generation of pro-inflammatory cytokines(TNF-${\alpha}$, IL-6). Results Cell viability showed that LOF extracts had no cytotoxicity in Raw 264.7 cells. The treatment with LOF extracts significantly decreased the generation of NO and pro-inflammatory cytokines(TNF-${\alpha}$, IL-6) in LPS-stimulated macrophage cells. Furthermore LOF extracts inhibited intracellular ROS generation dose dependently and reduced the expression of iNOS, COX-2 proteins. Conclusions These results showed that the LOF extracts had an anti-inflammatory effect on LPS-stimulated Raw 264.7 cells. These findings provide scientific support for the use of this Ligustrum obtusifolium S. for inflammatory-related diseases.

Alteration of Nitric Oxide Synthase and Guanylyl Cyclase Activity in Rats with Ischemia/Reperfusion Renal Injury

  • Bae, Eun-Hui;Kim, Soo-Wan
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.6
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    • pp.337-341
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    • 2006
  • The present study was designed to investigate the protein expression of nitric oxide synthase (NOS) and guanylyl cyclase (GC) activity in ischemia/perfusion (I/R) renal injury in rats. Renal I/R injury was experimentally induced by clamping the both renal pedicle for 40 min in Sprague-Dawley male rats. The renal expression of NOS isoforms was determined by Western blot analysis, and the activity of guanylyl cyclase was determined by the amount of guanosine 3', 5'-cyclic monophosphate (cGMP) formed in response to sodium nitroprusside (SNP), NO donor. I/R injury resulted in renal failure associated with decreased urine osmolality. The expression of inducible NOS (iNOS) was increased in I/R injury rats compared with controls, while endothelial NOS (eNOS) and neuronal NOS (nNOS) expression was decreased. The urinary excretion of NO metabolites was decreased in I/R injury rats. The cGMP production provoked by SNP was decreased in the papilla, but not in glomerulus. These results indicate an altered regulation of NOS expression and guanylyl cyclase activity in I/R-induced nephropathy.

Gold Sodium Thiomalate Inhibits iNOS Gene Expression in RAW 264.7 Macrophage: Differential Regulation by Gold Sodium Thiomalate and Sodium Salicylate (Gold Sodium Thiomalate에 의한 유도성 Nitric Oxide Synthase Gene의 발현억제: Gold 제제와 Sodium Salicylate의 차이점)

  • 임종호;배진영
    • Biomolecules & Therapeutics
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    • v.10 no.4
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    • pp.230-235
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    • 2002
  • Gold sodium thiomalate (GST, gold compound) is a widely used anti-arthritic, anti-rheumatic and anti-inflammatory drug that is considered a good alternative to sodium salicylate (NaSA) for individuals who cannot tolerate salicylates. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. Recent evidence suggests that anti-inflammatory effect of NaSA lies in the inhibition of iNOS, but nothing has been reported about the direct effect of iNOS expression by GST. The present study was designed to elucidate sequentially the action mechanisms of GST and NaSA on lipopolysaccharide (LPS) plus interferon-gamma (IFN-$\gamma$) induced iNOS expression in RAW 264.7 macrophages. Both GST and NaSA inhibited NO production and iNOS protein expression in a dose dependent manner. GST inhibited iNOS mRNA expression induced by LPS plus IFN-$\gamma$, whereas NaSA did not. These findings suggest that GST may exert anti-arthritic, anti-rheumatic and anti-inflammatory effect by inhibiting iNOS expression induced by LPS plus IFN-$\gamma$ at transcriptional level, whereas NaSA exert its effect by inhibiting iNOS expression at the translational or posttranslational level.

Antioxidant and anti-inflammatory activities from fruiting body extracts of Lyophyllum decastes

  • Ki Nam Yoon;Tae Soo Lee
    • Journal of Mushroom
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    • v.21 no.3
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    • pp.101-109
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    • 2023
  • Lyophyllum decastes has been used for culinary purpose. The present study was conducted to evaluate the antioxidant and anti-inflammatory effects from methanol, acetone, and hot water extracts of L. decastes fruiting bodies. The acetone and methanol extracts showed the higher 1,1-diphenyl-2-picryl-hydrazy radical scavenging activities than that of the hot water extract at 0.5-2.0 mg/mL and was comparable to the BHT, the positive control. The ferrous ion chelating effects of the mushroom extracts at 0.5-2.0 mg/mL were significantly higher than that of BHT. The reducing power of acetone extract (2.12) was significantly lower than that of BHT (2.73) at 2.0 mg/ mL. The mushroom extracts also showed inhibitory effects on production of nitric oxide (NO), and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide-induced murine macrophage cells in a concentration dependent manner. In vivo anti-inflammatory experiment on carrageenan-induced hind-paw edema of rat model, the acetone extract of the mushroom significantly suppressed the carrageenan-induced rat hind paw edema of rats in a dose dependently. The results suggest that the fruiting bodies of Lyophyllum decastes are a good natural resource of antioxidant and anti-inflammation.