• Natural Product Sciences
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• 제11권1호
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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.

• 동의생리병리학회지
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• 제17권3호
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• pp.771-776
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• 2003

The present study was conducted to evaluate the regulation mechanism of nitric oxide(NO) by water-extracted Cyperus rotundus (WCR) in RAW 264.7 macrophages. We investigated the effects of cell proliferation in mouse spleen cell and RAW 264.7 macrophages cells. WCR enhanced mitogenic activity in the dose-response manner in mouse spleen cells and RAW 264.7 macrophages cells. In nitric oxide (NO) synthesis by WCR, WCR alone had an effect on NO synthesis. It was found that the production of NO of RAW 264.7 cells stimulated with lipopolysaccharide (LPS) could be markedly inhibited by WCR. Inhibition of NO production was achieved by reducing inducible nitric oxide syntheses(iNOS) mRNA expression. The expression of IL-I gene by WCR was investigated using reverse transcription polymerase chain reaction (RT-PCR). In RT-PCR, IL-1 family(IL-1 α, IL-1β) expressions were induced by WCR. These finding suggested that regulation of NO production by WCR may be, at least in part, associated with the regulation of iNOS mRNA expression and IL-1 family gene expression.

• 동아시아식생활학회지
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• 제7권4호
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• pp.484-490
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• 1997

백삼성분이 탐식세포를 통한 면역반응조절에 어떠한 영향을 미치는가를 알아보기 위해 total saponin이나 ginsenoside Rb$_2$성분이 마우스 복강 탐식 세포의 증식과 nitric oxide(NO)분비 및 NOS 유전자 발현에 미치는 영향을 조사해 보았다. Total saponin 또는 ginsenoside Rb$_2$성분을 탐식세포 배양액에 0-256$\mu\textrm{g}$/$m\ell$ 농도로 첨가하여 배양한 후 $^3$H-thymidine incorporation법으로 분석을 실시한 결과 total saponin은 64$\mu\textrm{g}$/$m\ell$ 농도에서 세포내 DNA 합성을 증가시켰으며, ginsenoside Rb$_2$ 성분의 경우 16$\mu\textrm{g}$/$m\ell$ 또는 64$\mu\textrm{g}$/$m\ell$ 농도에서 DNA 합성이 증가되었다. 256$\mu\textrm{g}$/$m\ell$의 높은 농도에서 세포의 증식이 약간 저해되었지만 대조군에 비해 유의적인 감소는 보이지 않았다. NO 분비에 미치는 영향을 조사해 본 결과 20$\mu\textrm{g}$/$m\ell$ 농도의 백삼성분을 투여했을 때 NO분비가 대조군에 비해 유의적으로 증가하였다. Reverse transcription polymerase chain reaction (RT-PCR)을 이용하여 백삼성분에 의한NOS 유전자 발현의 정도를 조사한 결과 20$\mu\textrm{g}$/$m\ell$ 농도에서 nos gene발현이 대조군보다 증가되었다

• 셀메드
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• 제8권2호
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• pp.8.1-8.5
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• 2018

Nitric oxide (NO) is a small diffusible molecule which plays an important role in various physiological activities. NO is a notable molecule, functioning as a cytotoxic agent and cellular messenger. There has been considerable interest in NO production by activated macrophages because this gaseous metabolite plays a fundamental role in the cytotoxic and cytostatic effects of macrophages towards invasive micro-organisms and tumour cells. No is a bioactive free radical that has been implicated in many physiological functions, plays a critical role during inflammation and therefore constitutes a potential target for developing therapeutics for inflammatory diseases. The use of medicinal plants by the population has been an important alternative the resource in the treatment of various diseases. Its growing acceptance in the medical community has been due to the fact that several plants with biological activities have been scientifically investigated and their efficacy and safety have been proven. In this review, discussed suppressive effects of No production by traditional medicines in RAW 264.7 and THP-1 macrophages.

• Journal of Microbiology and Biotechnology
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• 제18권2호
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• pp.392-395
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• 2008

In an attempt to delineate the direct effect of arsenite-induced endothelial dysfunction on nitric oxide (NO) production, confluent bovine aortic endothelial cells (BAEC) were incubated with arsenite, and endothelial NO synthase expression and NO production were measured. Exposure of arsenite decreased NO production for up to 24h. This decrease was accompanied by decreases in cAMP, protein kinase A (PKA) activity, and furthermore, significant reduction of pCREB. In conclusion, this study is the first to demonstrate that exposure of arsenite decreases NO production by a reduction of pCREB and PKA activity that may be mediated by cAMP, leading to endothelial dysfunction.

• 대한약리학회지
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• 제32권3호
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• pp.389-397
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• 1996

위점막은 위강내에서 생성되는 독성이 강한 활성산소종에 노출된다. Nitric oxide는 glutathione의 항상성을 유지시킴으로써 acetaminophen 유도 간독성에 대한 보호효과를 나타내었다. 본 연구는 hydrogen peroxide로 인한 위선세포 손상에 대한 nitric oxide의 작용을 규명하고자 하였다. Hydrogen peroxide는 ${\beta}-D-glucose$와 glucose oxidase의 반응에 의해 생성시켰으며, 위선세포에 L-arginine, $N^{G}-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$을 전처리 한 후, 세포외로 유리되는 지질과산화물 및 nitrite를 정량하고 세포내 glutathione 함량을 측정하였다. 결과로서, glucose/glucose oxidase를 처리한 경우 glucose oxidase 농도의존적으로 지질과산화물 생성은 증가되었으며, nitrite 유리 및 glutathione 함량은 감소되었다. NO synthase의 기질인 L-arginine 전처리시 glucose/glucose oxidase에 의한 지질과산화 및 nitrite 유리 증가와 세포내 glutathione 감소등이 방지되었다. $N^G-nitro-L-arginine$ methyl ester 및 $N^G-nitro-L-arginine$등 NO synthase 억제제들은 세포손상에 보호효과를 나타내지 않았다. 결론적으로 nitric oxide는 hydrogen peroxide로 인한 세포손상에 대한 보호효과가 없으며, 이는 지질과산화 반응 및 세포내 glutathione 고갈등을 억제시킴으로써 이루어진다고 사료된다.

• 한국환경성돌연변이발암원학회지
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• 제22권3호
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• pp.183-186
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• 2002

Hypertension is a multifactorial disease. Both genetic and environmental factors have been implicated in its etiology. Since the impairment of nitric oxide (NOS) production plays an important role in the pathogenesis of hypertension, endothelial nitric oxide synthase (ecNOS) gene is supposed to be a candidate gene of hypertension. Our study group investigated the 27 bp insertion/deletion (Ins/Del) polymorphism of ecNOS gene in 99 Korean normotensives and 98 hypertensives, respectively. There was no significant association with any cardiovascular risk factors as well as hypertension in Koreans. The Ins/Del polymorphism of the ecNOS gene indicated the similar allele distribution among ethnic groups studied. Further studies using larger sample size and subject information is required to describe the general picture of the association between the ecNOS gene polymorphic loci and hypertension

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.196-196
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• 1998

Nitric oxide is involved in various physiological processes. Among isoforms of nitric oxide synthase, iNOS is partly responsible for inflammation and septic shock. During our continual search for anti-inflammatory flavonoids, we have found that flavonoids, especially flavones, possessed the inihibitory activity of NO production by iNOS from LPS-activated RAW 264.7 cell. In this study, flavonoids from Scutellaria radix were investigated for their inhibitory activity of nitric oxide production. It was found that wogonin, among tested flavonoids including baicalein, oroxylin A, skullcapflavone II, showed the strongest inhibition of nitric oxide production (IC$\sub$50/ = 17 uM). And this inhibition was, at least partly, due to down-regulation of iNOS enzyme induction, not due to direct inhibition of iNOS enzyme activity.

• 한국발생생물학회지:발생과생식
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• 제1권2호
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• pp.157-164
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• 1997

To study the regulation of porcine follicular cell apostosis by gonadotropin, steroid, and nitric oxide, we analyzed DNA fragmentation, the hallmark of apoptosis, and nitrite production of porcine granulosa cells. Dissected indiidual follicles from ovary were separated in size (small, 2-3 mm; medium, 5-6 mm; large, 7-8 mm) and isolated granulosa cells were classified morpholocally as atretic or nonatretic. Nitrite concentration was measured by mixing follicular fluids with an equal volume of Griess reagent. Follicular nitric oxide (NO) concentration of healthy follicles was higher than that of atretic follicles. Apoptotic DNA fragmentation was suppressed in non-apoptotic granulosa cells. Follicular apoptosis was induced by androgen but prevented by gonadotropin in vitro. Apoptosis was confined to the granulosa cells. But it was not clear whether apoptosis of granulosa cells were isolated, incubated with or without gonadotropin, androgen and sodium nitroprusside (SNP), respectively at $37^{\circ}C$ for 24 hrs. Cultured granulosa cells were used to extract genomic DNA and culture media was asssayed for nitrite concentration. Nitrite production of culture media was increased, while apoptotic DNA fragmentation was suppressed in PMSG, hCG, testosterone+SNP and SNP treated groups. Nitrite concentration in culture media was decreased, but apoptotic DNA fragmentation was induced in testosterone treated group. These data suggest that NO production and apoptosis may be involved of granulosa cell apoptosis induced by testosterone.

• Natural Product Sciences
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• 제23권2호
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• pp.92-96
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• 2017

A sesquiterpene was purified from Artemisia iwayomogi methanolic extract during the course of searching anti-inflammatory principle from medicinal plants. A sesquiterpene identified as armefolin inhibited the production of nitric oxide (NO) and attenuated inducible nitric oxide synthase (iNOS) protein level in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Armefolin also down-regulated mRNA expressions of iNOS and pro-inflammatory cytokines, interleukin-$1{\beta}$ and interleukin-6 in LPS-activated macrophages. Moreover, armefolin suppressed the degradation of inhibitory-${\kappa}B{\alpha}$ (I-${\kappa}B{\alpha}$) in LPS-activated macrophages. These data suggest that armefolin from A. iwayomogi can suppress the LPS-induced production of NO and the expression of iNOS gene through inhibiting the degradation of I-${\kappa}B{\alpha}$. Taken together, armefolin from A. iwayomogi might be a candidate as promising anti-inflammatory agent.