• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.326-333
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• 2020

Nitrate-nitrite-nitric oxide (NO) pathway is a major alternative source of NO and is essential for NO - dependent physiological functions in body. Food supplements having nitrate/nitrite can improve metabolic syndromes including hypertension through antioxidant activity or vasodilation. The purpose of this study was to observe the effects of fermented garlic (F. garlic) having high concentration of NO2- on changes in blood flow and nitric oxide synthesis in the cerebral cortex of rodents. The generation of nitric oxide detected by a chemi-luminescence detector was higher in F. Garlic compared with NaNO2 solution under artificial gastric juice with pH 2.0. Ether F. garlic or NaNO2 diluted with artificial cerebrospinal fluid was directly applied into around the needle probe of laser Doppler flow meter that was located on epidural surface of the cortex. Direct application of F. garlic resulted in increase of cerebral blood flow detected by a laser Doppler flow meter with a dose-dependent manner. Compared with NaNO2 solution, F. garlic produced changes in cerebral blood flow at lower concentration of NO2-. Pretreatment of methylene blue, a guanylyl cyclase inhibitor prevented upregulation of cerebral blood flow by the treatment of F. garlic. In addition, the application of F. garlic with 250, 500ppm of NO2- caused significantly the production of NO in the cortical tissue but NaNO2 solution with 500ppm of NO2- did not. In summary, these results suggested that F. garlic with high content of NO2- induce increase in cerebral blood flow through nitric oxide-dependent signal pathway.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.05a
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• pp.50-50
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• 2003

Nitric oxide (NO) has been studied and found to be an important intracellular modulator. The excess NO produced by the inducible nitric-oxide synthase (iNOS) is implicated in various inflammatory diseases and cellular injury. Inflammatory cytokines such as TNF- or IL-6 increase intracellular ceramide and ceramide may induce NO production and inflammation. (omitted)

• YAKHAK HOEJI
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• v.45 no.1
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• pp.16-22
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• 2001

Novel yakuchinone derivatives have been designed, synthesized and evaluated their inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages. From this study, some enone compounds have been found to be highly active in the assay. In view of the importance of NO in septic shock and inflammation, these compounds may be useful candidates for the development of new drug to treat endotoxemia and inflammation accompanying overproduction of NO.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.5
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• pp.1049-1054
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• 2009

The effect of Sacchromyces cerevisiae-Fermented Sophorae Radix water extract (SFS) on production of hydrogen peroxide and nitric oxide (NO) from mouse macrophage Raw 264.7 Cells treated with nicotine (1 mM) was investigated through this study. SFS (0, 25, 50, 100, 200, 400 ug/mL) was simultaneously treated with nicotine (1 mM) during culture of 4, 20, 24, 44, 48, 68, and 72 hr. And the intracellular productions of hydrogen peroxide were measured by dihydrorhodamine 123 (DHR) assay. NO production after 24 hr treatement was measured with Griess reagent assay. SFS restored the production of hydrogen peroxide and NO reduced by nicotine (1 mM) in Raw 264.7 Cells. These results suggests that SFS could be supposed to have the immunological activity concerned with macrophage's oxidative burst including hydrogen peroxide and NO.

• Archives of Pharmacal Research
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• v.26 no.4
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• pp.301-305
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• 2003

Nitric oxide (NO) is an important bioactive agent that mediates a wide variety of physiological and pathophysiological events. NO overproduction by inducible nitric oxide synthase (iNOS) results in severe hypotension and inflammation. This investigation is part of a study to discover new iNOS inhibitors from medicinal plants using a macrophage cell culture system. Two sesquiterpenes (1 and 2) were isolated from Artemisia iwayomogi (Compositae) and were found to inhibit NO synthesis ($IC_{50} 3.64 \mu g/mL and 2.81 \mu$g/mL, respectively) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Their structures were identified as 3-Ο-methyl-iso-secotanapartholide (1) and iso-secotanapartholide (2). Compounds 1 and 2 inhibited the LPS-induced expression of the iNOS enzyme in the RAW 264.7 cells. The inhibition of NO production via the down regulation of iNOS expression may substantially modulate the inflammatory responses.

• Journal of Chest Surgery
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• v.33 no.2
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• pp.132-138
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• 2000

Background: Inhaled nitric oxide therapy causes selective pulmonary vasodilation in congenital heart diseases with pulmonary hypertension. However discontinuation of inhaled nitric oxide therapy may be complicated by abrupt life-threatening rebound pulmonary hypertension(RPH) The purpose of this study was to prevent by comparing group I(without RPH n=13) and group II(with RPH n=6) to determine the risk factors involved inthe development of the RPH. Material and Method: Between Januarty 6, 1998 and April 14, 1999. we studied 19 consecutive children who were treated with inhaled nitric oxide for clinically significant pulmonary hypertension after an open heart surgery for congenital heart disease. the ratio of males and females was 12:7 ranging in age from 10 days to 6040 days(16 years) To identify the effects of nitric oxide between two groups we measured heart rate mean and systolic pulmonary arterial pressure mean and systolic systemic arterial pressure central venous pressure pH paO2/FiO2 and O2 saturation before and after the initiation and just before the withdrawal of the inhaled nitric oxide. result: In 6 of 19 patients(32%) withdrawal of inhaled nitric oxide caused RPH. In the two groups inhaled nitrix oxide decreased in pulmonary arterial pressure(PAP) without decreasing the systemic arterial pressure(SAP) and increased PaO2/FiO2 Compared with patients who had no RPH(group I) patients who had RPH(group II) were older in age (1204$\pm$1688 versus 546$\pm$1654 days p<0.05) received less nitric oxide therapy(34$\pm$18 versus 67$\pm$46 hours p<0.05) has shorter weaning process(5$\pm$3 versus 15一13 hours p<0.05) and received lowerconcentration of initial nitric oxide supply(11$\pm$8 versus 17$\pm$8 ppm p>0.05) and lower concentration just before the withdrawal nitric oxide(4.2$\pm$2.6 versus 5.6$\pm$2.6 ppm, p>0.05) Conclusion : We speculate that older age shorter of nitric oxide therapy shorter weaning process are the risk factors of RPH.

• The Korea Journal of Herbology
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• v.21 no.2
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• pp.165-173
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• 2006

Objectives : Coptidis Rhizoma has been known traditional medicine with antimicrobial activities. We investigated inhibitory effects of Coptidis Rhizoma extract on lipopolysaccharide(LPS)-induced nitric oxide production from mouse macrophages. Methods : After Coptidis Rhizoma extract was pretreated in BV2, mouse brain macrophages and RAW264.7 mouse macrophages, cells were activated with LPS. To investigate cytotoxicity Coptidis Rhizoma extract, cell viability was measured by MTT assay. The production of nitric oxide(NO) and inducible nitric oxide synthase(iNOS) was determined in each culture supernatant and mRNA by Griess reaction and RT-PCR. The production of $TNF-{\alpha}$ from cells was measured by ELISA. Results : Coptidis Rhizoma extract significantly inhibited LPS-induced NO production in BV2 and RAW264.7 cells. Coptidis Rhizoma extract also greatly suppressed mRNA expression of iNOS in BV2 and RAW264.7 cells activated by LPS. Conclusion : These data suggests that Coptidis Rhizoma extract may have an anti-inflammatory effect through the inhibition of NO production.

• Toxicological Research
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• v.24 no.3
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• pp.169-174
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• 2008

This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

• YAKHAK HOEJI
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• v.45 no.1
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• pp.116-124
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• 2001

Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.172-183
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• 1999

Background: Nitric oxide is a short-lived effector molecule derived from L-arginine by the nitric oxide synthase(NOS). Nitric oxide plays a role in a number of physiologic and pathophysiologic functions including host defense, edema formation, and regulation of smooth muscle tone. Some kinds of cells including macrophage are known to produce large quantities of nitric oxide in response to inflammatory stimuli such as interleukin-$1\beta$(IL-$1\beta$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), interferon-$\gamma$(IFN-$\gamma$) and lipopolysaccharide(LPS). Reactive oxygen species are also known to be important in the pathogenesis of acute cell and tissue injury such as acute lung injury model Methods: Using the RA W264.7 cells, we have examined the ability of oxidant hydrogen peroxide($H_2O_2$) to stimulate nitric oxide production and inducible NOS mRNA expression. Also, we have examined the effects of NOS inhibitors and antioxidants on $H_2O_2$ induced nitric oxide production. Results: Stimulation of RAW264.7 cells with combinations of 100 ng/ml IL-$1\beta$, 100 ng/ml TNF-$\alpha$, and 100 U/ml IFN-$\gamma$ or 100 U/ml IFN-$\gamma$ and $1{\mu}g/ml$ LPS induced the synthesis of nitric oxide as measured by the oxidation products nitrite($NO_2^-$) and nitrate($NO_3^-$). Addition of $250 {\mu}M-2$ mM $H_2O_2$ to the cytokines significantly augmented the synthesis of $NO_2^-$ and $NO_3^-$(p<0.05). When cells were incubated with increasing concentrations of $H_2O_2$ in the presence of IL-$1\beta$, TNF-$\alpha$ and IFN-$\gamma$ at constant level, the synthesis of $NO_2^-$ and $NO_3^-$ was dose-dependently increased(p<0.05). $N^G$-nitro-L-arginine methyl ester(L-NAME), dose dependently, significantly inhibited the formation of $NO_2^-$ and $NO_3^-$ in cells stimulated with LPS, IFN-$\gamma$ and $H_2O_2$ at constant level(p<0.05). Catalase significantly inhibited the $H_2O_2$-induced augmentation of cytokine-induced $NO_2^-$ and $NO_3^-$ formation(p<0.05). But, boiled catalase did not produce a significant inhibition in comparison with the native enzyme. Another antioxidant 2-mercaptoethanol and orthophenanthroline dose-dependently suppressed $NO_2^-$ and $NO_3^-$ synthesis(p<0.05). Northern blotting demonstrated that H:02 synergistically stimulated the cytokine-induced iNOS mRNA expression in RA W264.7. Conclusion: These results suggest that $H_2O_2$ contributes to inflammatory process by augmenting the iNOS expression and nitric oxide synthesis induced by cytokines.