• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.68-73
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• 2004

This study was performed to investigate the regulatory mechanism of cerebral blood How of adenosine $A_2$ receptor agonist in the rats, and to define whether its mechanism is mediated by nitric oxide (NO), adenylate cyclase and guanylate cyclase. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebal cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine $A_2$ receptor agonist [5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA; 4 umol/l)] increased cerebral blood flow. This effect of CPCA (4 umol/l) was blocked by pretreatment with NO synthase inhibitor [$N^G$-nitro-L-argine methylester (L-NAME; 140 umol/l)] and adenylate cyclase inhibitor [MDL-12,330 (20 umol/l)]. But the effect of CPCA (4 umol/l) was not blocked by pretreatment with guanylate cyclase inhibitor [LY-83,583 (10 umol/l)]. These results suggest that adenosine $A_2$ receptor increases cerebral blood How. It seems that this action of adenosine $A_2$ receptor is mediated via the NO and the activation of adenylate cyclase in the cerebral cortex of the rats.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.299-304
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• 2001

The effect of the nitric oxide synthase(NOS) inhibitor, $N^{G}$-nitro-L-arginine methyl ester (L-NAME), and the prostanoid synthesis inhibitor, indomethacin, on the vasodilatation produced in response to acetylcholine(Ach) on the isolated rabbit renal artery was examined. The vasodilatory reponses to Ach($10^{-8}-3{\times}10^{-5}M$) were completely absent in thevessel which the endothelium had previous been removed. L-NAME($10^{-4}M$) significantly reduced the vasodilatory reponse to the Ach($10^{-8}-3{\times}10^{-5}M$). When L-arginine ($10^{-3}M$) was also present in the organ bath along with L-NAME($10^{-4}M$), this inhibitory effect of L-NAME ($10^{-4}M$) on the vasodilatory response to Ach ($10^{-8}-3{\times}10^{-5}M$) was significantly attenuated, Indomethacin ($10^{-6}M$) did not significantly affect the vasodilatory responses to Ach ($10^{-8}-3{\times}10^{-5}M$). The inhibition by L-NAME ($10^{-4}M$) and indomethacin ($10^{-6}M$) on vasodilatory response to Ach was significantly greater than the inhibition due to L-NAME ($10^{-4}M$) alone. The present study has established that Ach induce relaxation via and endothelium-dependent mechanism, this relaxation to Ach involves both nitric oxide(NO) and prostanoid in the isolated rabbit renal artery.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1315-1321
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• 2008

Chan-Su (Venenum bufonis) has long been for a variety of other purposes including treatment of inflammation in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of Chan-Su on NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, Chan-Su inhibited the secretion of NO in BV2 microglial cells, without affecting cell viability, The protein level of inducible nitric oxide synthase (iNOS) was decreased by Chan-Su, And Chan-Su also inhibited production of prostaglandin E2 (PGE2) and expression of cyclooxygenase (COX)-2. Proinflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-12, were inhibited by Chan-Su in a dose-dependent manner. And Chan-Su inhibited the degradation of ${IkB-\alpha}$, which was considered to be inhibitor of nuclear factor $(NF)-{\kappa}B$, one of a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. These results suggest that Chan-Su could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $I{\kappa}B-{\alpha}$ degradation.

• Asia-pacific Journal of Multimedia Services Convergent with Art, Humanities, and Sociology
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• v.9 no.6
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• pp.443-450
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• 2019

Vicia amoena has traditionally been used to treat disease of rheumatism, arthralgia, muscular paralysis, abscess and eczema, and it has anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically in vestige acted so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of V. amoena using the ethanolic extract. To evaluate the anti-inflammatory effects, we examined the inflammatory mediators such as nitric oxide (NO) and prostaglandin E₂ (PGE₂) on RAW264.7 cells. Our results indicated that ethanolic extract of V. amoena significantly inhibited the LPS-induced NO and PGE₂ production in RAW264.7 cells. The ethanolic extract of V. amoena has inhibited the PGE₂ production by 88.0±0.8 % at the concentration of 40㎍/ml. This results showed that ethanol extract of V. amoena is expected to be a good candidate for development into source of inflammation inhibitor

• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.196-202
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• 2005

Nitric oxide (NO) is a small, diffusible, and highly reactive molecule, which plays dichotomous regulatory roles under physiological and pathological conditions. NO promotes apoptosis in some cells, and inhibits apoptosis in other cells. In the present study, we attempted to characterize the NO signaling pathway and cellular response in PC12 cells treated with cytokines. $IFN{\gamma}\;and\;TNF{\alpha}$ treatment resulted in a synergistic increase of nitrite accumulation, with the induction of inducible nitric oxide synthase (iNOS) in the PC12 cells. Moreover, as nitrite concentration increased, cell viability decreased. In order to explore MAP kinase involvement in nitric oxide production resultant from $IFN{\gamma}\;and\;TNF{\alpha}$ stimulation, we measured the activation of MAP kinase using specific MAP kinase inhibitors. PC12 cells pretreated with SB203580, a p38 MAP kinase-specific inhibitor, resulted in the inhibition of iNOS expression and NO production. However, PD98059, an ERK/MAP kinase-specific inhibitor, was not observed to exert such an effect. In addition, Stat1 activated by $IFN{\gamma}\;and\;TNF{\alpha}$ was interacted with p38 MAPK. These data suggest that p38 MAP kinase mediates cytokine-mediated iNOS expression in the PC12 cells, and Jak/Stat pathway interferes with p38 MAPK signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.357-362
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• 2003

Carbon monoxide (CO) is low molecular weight oxide gas that is endogenously produced under physiological conditions and interacts with another gas, nitric oxide (NO), to act as a gastrointestinal messenger. The aim of this study was to determine the effects of exogenous CO on L-type calcium channel currents of human jejunal circular smooth muscle cells. Cells were voltage clamped with 10 mM barium ($Ba^{2+}$) as the charge carrier, and CO was directly applied into the bath to avoid perfusion induced effects on the recorded currents. 0.2% CO was increased barium current ($I_{Ba}$) by $15{\pm}2$% ($mean{\pm}S.E.$, p<0.01, n=11) in the cells. To determine if the effects of CO on barium current were mediated through the cGMP pathway, cells were pretreated with 1-H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{mu}M$), a soluble guanylyl cyclase inhibitor, and exogenous CO (0.2%) had no effect on barium currents in the presence of ODQ ($2{\pm}1$% increase, n=6, p>0.05). CO mediates inhibitory neurotransmission through the nitric oxide pathway. Therefore, to determine if the effects of CO on L-calcium channels were also mediated through NO, cells were incubated with $N^G-nitro-L-arginine$ (L-NNA, 1 mM), a nitric oxide synthase inhibitor. After L-NNA pretreatment, 0.2 % CO did not increase barium current ($4{\pm}2$% increase, n=6, p>0.05). NO donor, SNAP ($20{\mu}M$) increased barium current by $13{\pm}2$% (n=6, p<0.05) in human jejunal smooth muscle cells. These data suggest that CO activates L-type calcium channels through NO/cGMP dependant mechanism.

• Plant Biotechnology Reports
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• v.2 no.2
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• pp.113-122
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• 2008

Nitric oxide (NO) affects the growth and development of plants and also affects plant responses to various stresses. Because NO induces root differentiation, we examined whether or not it is involved in increased ROS generation. Treatments with sodium nitroprusside (SNP), an NO donor, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), a specific NO scavenger, and $N{\omega}-nitro-{\text\tiny{L}}-arginine$ methyl ester hydrochloride (${\text\tiny{L}}-NAME$), an NO synthase (NOS) inhibitor, revealed that NO is involved in the adventitious root growth of mountain ginseng. Supply of an NO donor, SNP, activates NADPH oxidase activity, resulting in increased generation of $O_2{^{{\cdot}-}}$, which subsequently induces growth of adventitious roots. Moreover, treatment with diphenyliodonium chloride (DPI), an NADPH oxidase inhibitor, individually or with SNP, inhibited root growth, NADPH oxidase activity, and $O_2{^{{\cdot}-}}$ anion generation. Supply of the NO donor, SNP, did not induce any notable isoforms of enzymes; it did, however, increase the activity of pre-existing bands of NADPH oxidase, superoxide dismutase, catalase, peroxidase, ascorbate peroxidase, and glutathione reductase. Enhanced activity of antioxidant enzymes induced by SNP supply seems to be responsible for a low level of $H_2O_2$ in the adventitious roots of mountain ginseng. It was therefore concluded that NO-induced generation of $O_2{^{{\cdot}-}}$ by NADPH oxidase seems to have a role in adventitious root growth of mountain ginseng. The possible mechanism of NO involvement in $O_2{^{{\cdot}-}}$ generation through NADPH oxidase and subsequent root growth is discussed.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.3
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• pp.211-217
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• 2012

Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents ($I_{cap}$). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on $I_{cap}$. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on $I_{cap}$. The PKG inhibitor KT5823 prevented the inhibition of $I_{cap}$ by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

• Journal of Environmental Science International
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• v.19 no.12
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• pp.1323-1334
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• 2010

The effect of nitric oxide (NO) on antioxidant system and protective mechanism against oxidative stress under UV-B radiation was investigated in leaves of maize (Zea mays L.) seedlings during 3 days growth period. UV-B irradiation caused a decrease of leaf biomass including leaf length, width and weight during growth. Application of NO donor, sodium nitroprusside (SNP), significantly alleviated UV-B stress induced growth suppression. NO donor permitted the survival of more green leaf tissue preventing chlorophyll content reduction and of higher quantum yield for photosystem II than in non-treated controls under UV-B stress, suggesting that NO has protective effect on chloroplast membrane in maize leaves. Flavonoids and anthocyanin, UV-B absorbing compounds, were significantly accumulated in the maize leaves upon UV-B exposure. Moreover, the increase of these compounds was intensified in the NO treated seedlings. UV-B treatment resulted in lipid peroxidation and induced accumulation of hydrogen peroxide ($H_2O_2$) in maize leaves, while NO donor prevented UV-B induced increase in the contents of malondialdehyde (MDA) and $H_2O_2$. These results demonstrate that NO serves as antioxidant agent able to scavenge $H_2O_2$ to protect plant cells from oxidative damage. The activities of two antioxidant enzymes that scavenge reactive oxygen species, catalase (CAT) and ascorbate peroxidase (APX) in maize leaves in the presence of NO donor under UV-B stress were higher than those under UV-B stress alone. Application of 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3- oxide (PTIO), a specific NO scavenger, to the maize leaves arrested NO donor mediated protective effect on leaf growth, photosynthetic pigment and free radical scavenging activity. However, PTIO had little effect on maize leaves under UV-B stress compared with that of UV-B stress alone. $N^{\omega}$-nitro-L-arginine (LNNA), an inhibitor of nitric oxide synthase (NOS), significantly increased $H_2O_2$ and MDA accumulation and decreased antioxidant enzyme activities in maize leaves under UV-B stress. This demonstrates that NOS inhibitor LNNA has opposite effects on oxidative resistance. From these results it is suggested that NO might act as a signal in activating active oxygen scavenging system that protects plants from oxidative stress induced by UV-B radiation and thus confer UV-B tolerance.

• Natural Product Sciences
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• v.11 no.1
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• pp.16-21
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• 2005

Nitric Oxide (NO), derived from L-arginine, is produced by two types (constitutive and inducible) of nitric oxide synthase (NOS: cNOS and iNOS). The NO produced in large amounts by the iNOS is known to be responsible for the vasodilation and hypotension observed in septic shock, cancer metastasis and inflammation. The inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of herbal drugs which have been used for the treatment of inflammation in oriental medicine. We have screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. Among 82 kinds of extracts of herbal drugs, 35 extracts showed the potent inhibitory activity of NO production above 50% at the concentration of $50\;{\mu}g/mL$. The inhibitory activities of NO production were also evaluated for several solvent fractions at two different concentrations. Especially, hexane and EtOAc fractions of Alpinia officinarum, Angelica gigas, Ostericum koreanum, Saussurea lappa, Torilis japonica, and hexane fractions of Agrimonia pilosa, Machilus thunbergii, Hydrangea serrata, Magnolia obovata, Prunella vulgaris, Tussilago farfara, and EtOAC fractions of Perilla frutescence showed a significant activity at 10 and/or $25\;{\mu}g/mL$. In Western blot analysis, the hexane fractions ($5\;{\mu}g/mL$) of Magnolia obovata and Saussurea lappa, and EtOAc fractions ($20\;{\mu}g/mL$) of Hydrangea Serrata, Perilla frutescence and Torilis japonica inhibited the expression of iNOS protein in LPS-activated macrophages. These plants may be promising candidates for the study of the activity-guided purification of active compounds and might be useful for the treatment of inflammatory diseases and endotoxemia accompanying overproduction of NO.