• Title/Summary/Keyword: NO production inhibitors

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Anti-tumor Activity of Saponin Fraction of Platycodon gradiflourm through Immunomodulatory Effects associated with NO production in RAW264.7 cells (길경 사포닌 분획의 NO생성과 관련된 면역조절작용을 통한 대식세포의 항암활성에 미치는 효과)

  • Choung, Myoung-Gun;Sohn, Eun-Hwa
    • Korean Journal of Plant Resources
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    • v.24 no.5
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    • pp.557-563
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    • 2011
  • Platycodon grandiflorum (Korean name, Doraji) has been widely used in traditional herbal medicine as an expectorant for pulmonary disease and a remedy for respiratory disorders in Asia. Here, we investigated the effects of BtOH extract saponin fraction of P. gradiflourm (PGS) on phagocytosis and anti-tumor activity with related cytokine productions in RAW264.7 macrophage cells. The results showed that PGS increased phagocytosis, anti-tumor activity, TNF-${\alpha}$ and nitric oxide (NO) production without direct tumor cell cytotoxicity. To further investigate whether NO is involved in anti-tumor and phagocytic activities of PGS, cells were co-treated with specific iNOS inhibitors, L-NIL (N6-(1-iminoethyl)-L-lysine, dihydrochloride), to block NO production. PGS decreased anti-tumor activity in L-NIL-treated cells, whereas phagocytic activity was not inhibited under the same conditions, indicating that the anti-tumor activity by PGS appears to be conducted by NO. These findings suggest that P. grandiflorum could be used a potential nutrition therapeutic agent for cancer patients.

Src Kinase Regulates Nitric Oxide-induced Dedifferentiation and Cyc1ooxygenase-2 Expression in Articular Chondrocytes via p38 Kinase-dependent Pathway

  • Yu, Seon-Mi;Lee, Won-Kil;Yoon, Eun-Kyung;Lee, Ji-Hye;Lee, Sun-Ryung;Kim, Song-Ja
    • IMMUNE NETWORK
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    • v.6 no.4
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    • pp.204-210
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    • 2006
  • Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression. Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin $E_2\;(PGE_2)$ was determined by using a $PGE_2$ assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively. Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and $PGE_2$ production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and $PGE_2$ production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may playa role in the inflammatory responses of arthritic cartilage. Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1.

The Effects of Whitening Compoments on Human Melanocytes on virto

  • Cho, Joon-Hwan;Lee, Ki-Moo;Kim, Nam-Soo;Kang, Won-Hyoung
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.23 no.3
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    • pp.115-121
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    • 1997
  • To identify inhibitors of melanogenesis, we compared the effects of 5 compounds on mushroom tyrosinase, human melanocytic tyrosinase activity and melanin content. The cytotoxicyty of the components were also tested on cultured human melanoctes. Kojic acid showed marked inhibitory effect both on mushroom and human tyrosinase activity. This action of kijic acid is stronger than that of ascorbic acid. Arbutin inhibited human tyrosinase activity of cultured melanocytes although it had slightly inhibitory effect on mushroom tyrosinase activity. Azelaic acid had no effect on human tyrosinase activity. Melanin production was inhibited significantly by kojic acid and tranexamic acid. MTT assay showed that all of the compounds were non-cytotoxic to melanocytes at the concentrations tested. These results suggest that the effect of kojic acid on cultured meanocytes involve inhibition of tyrosinase activity and melanogenesis without affection the cell number.

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Effects of Inhibition on Formation and Growth of Polymer in Butadiene Extraction Unit (Butadiene Extraction Unit 내의 Polymer 생성 억제 효과)

  • Im, Gyeong
    • The Journal of Natural Sciences
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    • v.5 no.2
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    • pp.63-73
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    • 1992
  • There are many methods of obtaining butadiene described in the literature. In the america it is produced largely from petroleum gases, i.e., by catalytic dehydrogenation of butene of butene-butane mixtures. Butadiene can be recovered from the $C_4$ residue of an olefin plant by distilling off a fraction containing most of the butadiene, catalytically hydrogenating the higher acetylenes to olefins and separating the product from other olefins and isobutane by extraction. Also it can be obtained by cracking naphtha and light oil. Among the individual dienes of commercial importance, 1, 3-butadiene is of first importance. It is used primarily for the production of polymers.In the present paper, it was investigated for a effect of the formation and the growth inhibition of popped corn polymer in butadiene extraction unit. As a result of study, inhibitors, $NaNO_2$ and TBC were good effective for inhibition of the formation and growth in popcorn polymer. The rational formula of popcorn polymer obtained was $(C_4H_6)_x$.

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Newly Synthesized Phosphodiesterase 4 (PDE4) Inhibitor, DWP205505, Inhibits TNF-$\alpha$ Secretion and mRNA Expression

  • Lee, Suk-Kyeong;Lee, Sun-A;Byun, Hye-Sin;Cho, Mi-La;Kim, Wan-Uk;Park, Sung-Hwan;Cho, Chul-Soo;Joo, Young-Shil;Lee, Shin-Seok;Yoo, Eun-Sook;Son, Ho-Jung;Kim, Ho-Youn
    • Journal of Microbiology and Biotechnology
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    • v.9 no.1
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    • pp.106-112
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    • 1999
  • The therapeutic potential of phosphodiesterase 4(PDE4) inhibitors in inflammatory diseases including some autoimmune diseases has been explored recently with some hopeful results. These PDE4 inhibitors are thought to show their anti-inflammatory effect by down-regulating tumor necrosis factor-a (TNF-$\alpha$) production in lymphocytes and macrophages. A high concentration of TNF-$\alpha$has been found in rheumatoid arthritis (RA) synovium and reducing TNF-$\alpha$using biological agents was proven to be an effective RA treatment. To test the possibility of using PDE4 inhibitors for RA treatment, the effects of a newly synthesized PDE4 inhibitor, DWP205505, on TNF-$\alpha$ and IL-10 production was tested in cells isolated from normal peripheral blood and rheumatoid arthritis synovial fluid. Cytokine production was assayed at the protein level by sandwich enzyme-linked immunosorbent assay (ELISA) and at the mRNA expression level by semi-quantitative RT-PCR. Another PDE4 inhibitor, RP73401, was used for comparison. DWP205505 and RP73401 had no harmful effect on cell viability up to 10 $\mu$M concentration during the 24 h culture period. DWP205505 as well as RP73401 significantly reduced TNF-$\alpha$ secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (pBMC) and synovial fluid mononuclear cells (SFMC). The effect of DWP205505 or RP73401 treatment on the mRNA expression of TNF-$\alpha$ was also studied in LPS-stimulated PBMC and SFMC. TNF-$\alpha$ mRNA expression was increased by LPS stimulation and both of the PDE4 inhibitors suppressed TNF-$\alpha$ mRNA expression. For interleukin-l0 (IL-l0), a little different results were obtained from PBMC and SFMC; IL-l0 secretion was unaffected by LPS stimulation and only minimally affected by both of the PDE4 inhibitors in PBMC. In unstimulated SFMC, DWP205505 and RP73401 slightly enhanced IL-10 secretion, while they reduced IL-l0 secretion from LPS-stimulated SFMC where IL-l0 secretion was a lot higher than unstimulated SFMC. These results suggest that the newly synthesized PDE4 inhibitor DWP205505 may have anti-rheumatoid arthritis activity.

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Neuroprotective Effect of Wogonin: Potential Roles of Inflammatory Cytokines

  • Piao, Hua-Zi;Jin, Shun-Ai;Chun, Hyang-Sook;Lee, Jae-Chul;Kim, Won-Ki
    • Archives of Pharmacal Research
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    • v.27 no.9
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    • pp.930-936
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    • 2004
  • Wogonin (5,7-dihydroxy-8-methoxyflavone), an active component originated from the root of Scutellaria baicalensis Georgi, has been reported to possess antioxidant and anti-inflamma-tory properties. In this study, we investigated the neuroprotective effect of wogonin in a focal cerebral ischemia rat model. Wogonin markedly reduced the infarct volume after 2 h middle cerebral artery occlusion followed by 22 h reperfusion. Wogonin decreased the production of nitric oxide and inflammatory cytokines such as TNF-$\alpha$ and IL-6 in lipopolisaccharide-stimu-lated microglial cells. While wogonin reduced the activity of NF-$textsc{k}$B, it did not change the activ-ity of mitogen-activated protein kinases family members, p38, ERK and JNK. The lipopolisaccharide-stimulated production of NO and cytokines was significantly blocked by vari-ous kinds of NF-$textsc{k}$B inhibitors such as N-acetyl cysteine, pyrrolidinedithiocarbamate and MG-132. The data may indicate that wogonin has neuroprotective effect by preventing the over-activation of microglial cells, possibly by inactivating NF-$textsc{k}$B signaling pathway

Preventing Extracellular Diffusion of Trigeminal Nitric Oxide Enhances Formalin-induced Orofacial Pain

  • Jung, Hwi-Seok;Jeon, Hong-Bin;Jeon, Ik-Sung;Lee, Bum-Jun;Yoo, Hyun-Woo;Ahn, Dong-Kuk;Youn, Dong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.379-383
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    • 2009
  • Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.

Hydroquinone, a Reactive Metabolite of Benzene, Reduces Macrophage-mediated Immune Responses

  • Lee, Ji Yeon;Kim, Joo Young;Lee, Yong Gyu;Shin, Won Cheol;Chun, Taehoon;Rhee, Man Hee;Cho, Jae Youl
    • Molecules and Cells
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    • v.23 no.2
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    • pp.198-206
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    • 2007
  • Hydroquinone is a toxic compound and a major benzene metabolite. We report that it strongly inhibits the activation of macrophages and associated cells. Thus, it suppressed the production of proinflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-3, IL-6, IL-10, IL-12p40, IL-23], secretion of toxic molecules [nitric oxide (NO) and reactive oxygen species (ROS)] and the activation and expression of CD29 as judged by cell-cell adhesion and surface staining experiments. The inhibition was due to the induction of heme oxygenase (HO)-1 in LPS-activated macrophages, since blocking HO-1 activity with ZnPP, an HO-1 specific inhibitor, abolished hydroquinone's NO inhibitory activity. In addition, hydroquinone and inhibitors (wortmannin and LY294002) of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway had very similar inhibitory effects on LPS-induced and CD29-mediated macrophage responses, including the phoshorylation of Akt. Therefore, our data suggest that hydroquinone inhibits macrophage-mediated immune responses by modulating intracellular signaling and protective mechanisms.

Intracellular Signaling Pathways for Type II IgE Receptor (CD23) Induction by Interleukin - 4 and Anti - CD40 Antibody

  • Kim, Hyun-Il;Park, Hee-Jeoung;Lee, Choong-Eun
    • BMB Reports
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    • v.30 no.6
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    • pp.431-437
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    • 1997
  • Since the role of CD40 on the interleukin-4(IL-4) -induced B cell activation has been strongly implicated in the agumentation of IgE production and response, we have investigated the intracelluar signaling pathways utilized by IL-4 and CD40 for type II IgE receptor (CD23) expression. IL-4 and anti-CD40 antibody treatment of human B cells, independently caused a rapid induction of CD23 gene activation within 2 h. There was a noticeable synergism between the action of the two agents inducing CD23 expression: the addition of anti-CD40 to the IL-4-treated culture significantly agumented the IL-4-induced CD23 on both mRNA and surface protein levels, and the inclusion of IL-4 in the anti-CD40-treated cells caused a further increase of CD23 expression far above the maximal level induced by anti-CD40. Protein tyrosine kinase (PTK) inhibitors effectively suppressed the both IL-4- and anti -CD40-induced CD23 expression. whereas protein kinase C (PKC) inhibitors had no effects. Electrophoretic mobility shift assays (EMSA) have shown that IL-4 and anti-CD40 induce the activation of NF-IL-4 and $NF-_{K}B$, respectively, binding to the CD23 promoter, both in a PKC-independent and PTK-dependent manner. These data suggest that the synergistic activation of CD23 gene expression by IL-4 and anti-CD40 is mediated by co-operative action of distinct nuclear factors. each of which is rapidly activated via PKC-independent and PTK-dependent process.

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Green synthesis of silver nanoparticles to the microbiological corrosion deterrence of oil and gas pipelines buried in the soil

  • Zhi Zhang;Jingguo Du;Tayebeh Mahmoudi
    • Advances in nano research
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    • v.15 no.4
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    • pp.355-366
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    • 2023
  • Biological corrosion, a crucial aspect of metal degradation, has received limited attention despite its significance. It involves the deterioration of metals due to corrosion processes influenced by living organisms, including bacteria. Soil represents a substantial threat to pipeline corrosion as it contains chemical and microbial factors that cause severe damage to water, oil, and gas transmission projects. To combat fouling and corrosion, corrosion inhibitors are commonly used; however, their production often involves expensive and hazardous chemicals. Consequently, researchers are exploring natural and eco-friendly alternatives, specifically nano-sized products, as potent corrosion inhibitors. This study aims to environmentally synthesize silver nanoparticles using an extract from Lagoecia cuminoides L and evaluate their effectiveness in preventing biological corrosion of buried pipes in soil. The optimal experimental conditions were determined as follows: a volume of 4 ml for the extract, a volume of 4 ml for silver nitrate (AgNO3), pH 9, a duration of 60 minutes, and a temperature of 60 degrees Celsius. Analysis using transmission electron microscopy confirmed the formation of nanoparticles with an average size of approximately 28 nm, while X-ray diffraction patterns exhibited suitable peak intensities. By employing the Scherer equation, the average particle size was estimated to be around 30 nm. Furthermore, antibacterial studies revealed the potent antibacterial activity of the synthesized silver nanoparticles against both aerobic and anaerobic bacteria. This property effectively mitigates the biological corrosion caused by bacteria in steel pipes buried in soil.