• Environmental Analysis Health and Toxicology
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• 제18권4호
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• pp.249-254
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• 2003

본 연구는 환경호르몬(endocrine disruptors)으로 분류되었으며, 에스트로젠 화합물의 특성을 지닌 4-Nonylphenol (NP)이 설치류 Pituitary 세포 중 성장호르몬을 분비하는 GH3 세포의 Nitric oxide(NO)을 증가시키는 작용기전을 규명코자 수행되었다 먼저 GH3세포에 NP처리 농도에 따른 NO의 생성을 측정한 결과 NP처리농도 의존적으로 증가시켰다. 이러한 NO의 증가가 genomic action인지를 확인하기 위해 GH3세포의 NO를 증가시키는 효소인 neuronal oxide synthase의 단백질량을 측정한 결과 GH3세포에서 NP에 의한 nNOS의 단백질의 변화는 없었다. 에스트로젠 화합물인 NP가 에스트로젠 리셉터 (ER)와의 관계를 조사하기 위해 ER억제제(ICI 168,780)클 처리한 경우 NP에 의해 증가한 NO가 감소하였다. 또한 유전자 전사억제제인 actinomycin D 및 단백질 발현 억제제인 cycloheximide을 처리한 경우는 NP에 의한 NO 증가억제효과가 없었다. 이러한 결과를 종합해 볼 때 GH3 세포에서 NP는 ER을 매개한 non-genomic action에 의해 NO를 증가키는 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제62권4호
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• pp.308-313
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• 2007

연구배경: 패혈증에서 Nitric oxide 스테로이드 호르몬은 혈역학적 변화와 염증반응에 관여하는데 이 두 인자는 서로 상관성이 있는 것으로 알려지고 있다. 하지만 실제 환자에서 서로의 상관성이나 임상적 의의는 연구가 부족한 실정이다. 방법: 패혈증 환자 26예와 대조군 14예를 대상으로 혈중 총 NO와 혈중 코티졸 농도를 측정하였고 이어서 제 3, 5, 7병일에도 연속적으로 측정을 하였다. 결과: 패혈증 환자군에서 초기 혈중 코티졸 및 총 NO 농도는 대조군에 비하여 유의하게 증가하였고 경증 패혈증에 비하여 중증 패혈증 환자군에서 유의하게 높았다. 초기 혈중 총 NO의 농도는 APACHE II 점수, 정맥혈 lactate 농도와 상관성이 있었다. 패혈증의 시간의 경과에 따라 혈중 NO 농도는 제 1병일, 제 5병일, 제 7병일에 혈중 코티졸의 농도와 유의한 상관성이 있었다. 결론: 패혈증 환자들에서 혈중 NO와 코티졸 농도는 증가되어 있었으며, 경과에 따라 서로 유의한 상관성이 지속되었다. 상호작용기전에 대하여는 추가적인 연구가 필요할 것이다.

• 생약학회지
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• 제38권2호통권149호
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• pp.170-175
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• 2007

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO$^-$), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. We tried to evaluate the effects of two kinds of varieties of Perilla frutescens var japnica Hara on the NO production in lipopolysaccharide (LPS)-activated microglia. The perilla cultivars of Namcheondeulkkae (NC) and Boradeulkkae (BR) were developed by pure line from the local variety and by a cross between 'deulkkae' and 'chajogi', respectively. Spirit, hexane, chloroform and butanol fractions of the leaves of NC and BR inhibited the production of NO in LPS-activated microglia. The fractions of BR showed stronger activity than NC and the spirit extracts was the most potent in both cultivars. The solvent fractions of BR suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells. Moreover, the extracts of NC and BR showed the activity of peroxynitrite scavenging in cell free bioassay system. These results imply that Namcheondeulkkae and Boradeulkkae might have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

• Archives of Pharmacal Research
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• 제29권2호
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• pp.145-151
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• 2006

We investigated the effects of Ginsenoside $R_e$ on human sperm motility in fertile and asthenozoospermic infertile individuals in vitro and the mechanism by which the Ginsenosides play their roles. The semen samples were obtained from 10 fertile volunteers and 10 asthenozoospermic infertile patients. Spermatozoa were separated by Percoll and incubated with 0, 1, 10 or $100\;{\mu}M$ of Ginsenoside $R_e$. Total sperm motility and progressive motility were measured by computer-aided sperm analyzer (CASA). Nitric oxide synthase (NOS) activity was determined by the $^{3}H$-arginine to $^{3}H$-citrulline conversion assay, and the NOS protein was examined by the Western blot analysis. The production of sperm nitric oxide (NO) was detected using the Griess reaction. The results showed that Ginsenoside $R_e$ significantly enhanced both fertile and infertile sperm motility, NOS activity and NO production in a concentration-dependent manner. Sodium nitroprusside (SNP, 100 nM), a NO donor, mimicked the effects of Ginsenoside $R_e$. And pretreatment with a NOS inhibitor $N^{w}$-Nitro-L-arginine methyl ester (L-NAME, $100\;{\mu}M$) or a NO scavenger N-Acetyl-L-cysteine (LNAC, 1 mM) completely blocked the effects of Ginsenoside $R_e$. Data suggested that Ginsenoside $R_e$ is beneficial to sperm motility, and that induction of NOS to increase NO production may be involved in this benefit.

• Journal of Korean Neurosurgical Society
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• 제38권3호
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• pp.221-226
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• 2005

Objective : Reactive oxygen metabolites and polymorphonuclear leukocytes have been implicated in the pathophysiology of reperfusion injury. The mechanisms involved in superoxide-mediated leukocyte adherence remain unclear, however, nitric oxide[NO] may contribute to this response. The present study is undertaken to elucidate mechamisms controlling NO based mechanisms that regulated leukocyte-endothelial interactions in the cerebral vasculature after global cerebral ischemia and reperfusion. Methods : Pial venular leukocyte adherence of anesthetized newborn piglets was quantified by in situ fluorescence videomicroscopy through closed cranial windows during basal conditions and during 2hours of reperfusion after global ischemia induced by 9minutes of asphyxia. Nitric oxide synthase[NOS] was inhibited by local window superfusion of L-nitroarginine[NA]; superfusion of sodium nitroprusside[SNP] was used to donate NO. Results : The mean number of adherent leukocytes to cerebral venules in the 9minutes asphyxia and 2hours reperfusion group were $161{\pm}19$ compared with $13{\pm}4$ in the nonasphyxial group. Superfusion of L-NA through the cranial window for 2hours resulted in leukocyte adherence similar to that observed during the initial 2hours of reperfusion after asphyxia. Leukocyte adherence was not additionally increased in asphyxic animal treated with L-NA. SNP inhibited asphyxia induced leukocyte adherence back to control levels. Conclusions : Nitric oxide inhibits leukocyte adherence to cerebral venules during the initial hours of reperfusion after asphyxia, and that NO supplementation inhibit asphyxia induced leukocyte adherence back to control levels. These results indicate that NO is an important factor in ischemia-reperfusion induced leukocyte adherence.

• 약학회지
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• 제57권6호
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• pp.388-393
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• 2013

Previously, we have reported that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, increased melanin synthesis through intracellular $Ca^{2+}$ release in B16 cells. In this study we investigated the possible involvement of nitric oxide (NO) in the mechanism of lovastatin-induced melanogenesis. Lovastatin elevated NO formation in a dose-dependent manner. Treatment with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), precursors of cholesterol, did not significantly alter the lovastatin-induced NO production, suggesting that inhibition of cholesterol metabolism may not be involved in the mechanism of this action of lovastatin. Both NO formation and melanogenesis induced by lovastatin was significantly suppressed by treatment with $N^G$-nitro-L-arginine methyl ester (L-NAME) and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide (cPTIO), an inhibitor of NO synthase and a NO scavenger, respectively. The lovastatin-induced NO production was significantly affected not by EGTA, an extracellular $Ca^{2+}$ chelator, but by an intracellular $Ca^{2+}$ chelator (BAPTA/AM) and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular $Ca^{2+}$ release in B16 cells. These results further suggest that lovastatin may be a good candidate for the therapeutic application of various hypopigmentation disorders.

• 동의생리병리학회지
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• 제18권5호
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• pp.1512-1515
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• 2004

In this study, we investigated in vitro nitric oxide (NO) scavenging effect on nine herbal extracts using an NO donor S-nitroso-N-acetylpenicillamine (SNAP) compared with vitamin C. All herbal extracts effectively reduced the generation of NO radicals in a dose-dependant manner and over 65% in 10h. Especially, Ephedrae herba, Carthami flos and Lonicerae flos declined over 75% of NO scavenging effect, suggested that the herbal extracts are the powerful free radical scavengers and may be effective in clinical applications.

• Journal of Applied Biological Chemistry
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• 제52권4호
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• pp.212-215
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• 2009

The inhibitory effects of Curcuma longa rhizome-derived materials against nitric oxide (NO) production were assessed. The inhibitory effect (57%) on NO production was evidenced by the methanol extract of C. longa at $1\;{\mu}g/mL$. In the fractionation of the methanol extract, the ethyl acetate fraction evidenced an inhibitory effect greater than 62.1% at $1\;{\mu}g/mL$. The active constituent was identified as curcumin. Curcumin exerted potent inhibitory effects of 78.7 and 65.7% at concentrations of 1 and $0.5\;{\mu}g/mL$, respectively. Furthermore, the inhibitory effect of ar-turmerone was measured as 31.3 and 15.8% at 1 and $0.5\;{\mu}g/mL$, respectively. The iNOS expression-suppressive effects of curcumin were assessed via western blot analysis. Our results suggest that curcumin and ar-turmerone may prove useful in the development of new types of NO inhibitors.

• BMB Reports
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• 제44권11호
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• pp.699-704
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• 2011

Nitric oxide (NO) is a critical biological mediator involved in numerous diseases. However, the short lifetime of this molecule in biological conditions can make its study in situ complicated. Here, we review some recent results on the role of NO in angiogenesis, obtained using a biocompatible microelectrode array. This simple system allowed for the quick and easy quantification of NO released from cells grown directly on the surface of the sensor. We have used this technology to demonstrate that angiogenin induces NO release, and to partially elucidate its intracellular transduction pathway.

• Natural Product Sciences
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• 제18권3호
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• pp.141-146
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• 2012

Veronica peregrina (Scrophylariaceae) has been widely used as a Korean traditional medicine for the treatment of various pathological conditions including infection, hemorrhage and gastric ulcer. In the current study, we investigated the inhibitory effect of methanolic extracts of V. Peregrina (VPM) on the LPS-mediated nitric oxide (NO) production in mouse (C57BL/6) peritoneal macrophages. NO production was significantly down-regulated by the treatment of VPM dose dependently. To evaluate the mechanism of the inhibitory action of VPM on NO production, we performed iNOS enzyme activity assay and checked the change of inducible nitric oxide synthase (iNOS) levels by Western blotting. Although VPM did not affect iNOS enzyme activity, iNOS protein expression was attenuated by VPM indicating VPM inhibits NO production via suppression of iNOS enzyme expression. In addition, VPM attenuated the expression of another pro-inflammatory mediator such as cyclooxygenase-2 (COX-2) in a dose dependent manner. We also found that VPM can reduce trypsin-induced paw edema in mice. Based on this study, we suggest that V. peregrina may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.