• 동의생리병리학회지
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• 제22권5호
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• pp.1202-1209
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• 2008

Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}\;{O_2}^-$) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

• 대한한의학회지
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• 제30권1호
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.318.3-319
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• 2002

Peroxynitrite(ONOO-), formed from the reaction of superoxide(O2-) and nitric oxide(NO), is a potent oxidant that contributes to oxidation of various cellular constituents including lipids. amino acids, sulphydryls and nucleotides. It can cause cellular injury such as DNA fragmentation and apoptotic cell death. Also. the toxicity of ONOO- has been reported to be involved in inflammatory and nurodegenerative diseases such as Alzheimer's disease, Parkinson's disease. and atherosclerosis. (omitted)

• Natural Product Sciences
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• 제22권1호
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• pp.1-12
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• 2016

Compositional differences in flavonoids are varied in the big family of Compositae. By summarizing our previous analytical studies and other scientific evidences, new strategy will be possible to further analyze flavonoids and utilize them for human health. The HPLC analytical method has been established in terms of linearity, sensitivity, accuracy, and precision. Herbs of the family of Compositae have considerable amounts of peroxynitrite ($ONOO^-$)-scavenging effects and their phenolic substances. These effects may contribute to the prevention of disease associated with excess production of $ONOO^-$, depending on the high content of flavonoid substances.

• Archives of Pharmacal Research
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• 제28권12호
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• pp.1333-1336
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• 2005

A new lavandulylated flavonoid, 8-lavandulylkaempferol (1), was isolated from the roots of Sophora f1avescens AITON (Leguminosae). The structure of this compound was determined via spectroscopic analysis. Compound 1 was determined to be a scavenger on both 1, 1-diphenyl­2-picrylhydrazyl radicals and $ONOO^{-}$.

• 한국지반환경공학회 논문집
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• 제13권2호
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• pp.75-81
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• 2012

NDMA는 잠재적인 발암 물질로 잘 알려져 있기 때문에 UV를 활용한 처리기술과 분해경로에 대해 많은 연구가 이루어졌다. 그러나 NDMA가 ${NO_2}^-$, ${NO_3}^-$ 와 같은 산화물을 형성하는 메커니즘은 아직 명확하게 알려져 있지 않다. 본 연구에서는 NDMA의 광반응에 의해 생성되는 핵심 반응기들을 검토하였다. 주요 반응기들에 대한 연구는 질소 산화물들의 형성과 메탄올과 NDMA의 광분해에 의해 형성되는 미지의 반응기들 사이에서의 반응을 통하여 간접적으로 수행하였다. NDMA의 직접적인 UV 광반응에 의해서 생성된 $ONOO^-$ 가 질소 산화물(중간생성물)들의 산화로 인한 ${NO_2}^-$와 ${NO_3}^-$ 의 핵심 반응기인 것으로 확인되었다.

• 한국자원식물학회지
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• 제21권1호
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• pp.91-95
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• 2008

본 연구에서는 ${O_2}^-,{\cdot}OH$ radical, NO, $ONOO^-$ 자유라디칼을 유발시키는 in vitro assay system과 free radical-induced oxidative stress에 의한 단백질 손상에 대한 진흙버섯속에 속하는 상황버섯 물 추출물의 항산화 효과를 측정하였다. 상황버섯 물 추출물의 ${O_2}^-,{\cdot}OH$ radical, NO, $ONOO^-$ 자유라디칼 억제효과에서는 실험에 사용된 양성 대조물 보다는 낮게 나타났으나 모든 실험계에서 대조군에 비해 뚜렷하게 자유라디칼 소거효과를 나타냈다. 또한 상황버섯 물 추출물은 산화적 스트레스에 의한 단백질 손상 억제효과에서도 대조군에 비해 명확한 저해효과를 나타냈다. 그러므로 상황버섯의 항산화 효과는 상황버섯의 약리학적 효능을 설명하는데 중요한 기초 자료라고 사료된다.

• Archives of Reconstructive Microsurgery
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• 제15권1호
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• pp.1-9
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• 2006

The purpose of this study is to determine the effects of selective inducible nitric oxide synthase (iNOS) inhibitor N-[3-aminomethyl]benzyl]acetamidine (l400W) on the reperfused cremaster muscle. The extracellular superoxide dismutase knockout ($EC-SOD^{-/-}$) mice was used to make the experimental window for ischemia-reperfusion injury. The muscle was exposed to 4.5 h of ischemia followed by 90 min of reperfusion and the mice received either 3 mg/kg of 1400W or the same amount of phosphate buffered saline (PBS) subcutaneously at 10 min before the start of reperfusion. The results showed that 1400W treatment markedly improved the recovery of the vessel diameter and blood flow in the reperfused cremaster muscle compared to that of PBS group. Histological examination showed reduced edema in the interstitium and muscle fiber, and reduced nitrotyrosine formation (a marker of total peroxinitrite ($ONOO^-$) in 1400W-treated muscle compared to PBS. Our results suggest that iNOS and $ONOO^-$ products are involved in skeletal muscle I/R injury. Reduced I/R injury by using selective inhibition of iNOS is perhaps via limiting cytotoxic $ONOO^-$ generation, a reaction product of nitric oxide (NO) and superoxide anion ($O_2^-$). Thus, inhibition of iNOS appears to be a good treatment strategy in reducing clinical I/R injury.

• 동의생리병리학회지
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• 제26권4호
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• pp.483-490
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• 2012

This study was designed to identify the effects of Polygoni cuspidati Radix(PCR) on the generation of superoxide anion radicals (${\cdot}O_2{^-}$), nitric oxide (NO), peroxynitrite ($ONOO^-$) in the renal epithelial cells of mouse(LLC-$PK_1$). The effects of PCR on the expression of inflammation-related proteins, IKK-${\alpha}$, phospho-$I{\kappa}B-{\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, IL-$1{\beta}$, VCAM-1, were examined by western blotting. For this study, the fluorescent probes, namely dihydrorhodamine 123 (DHR 123), 2',7'-dichloro dihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) were used. Protein expression levels of IKK-${\alpha}$, phospho-$I{\kappa}B-{\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, IL-$1{\beta}$, VCAM-1 were assayed by western blot. PCR reduced $H_2O_2$-induced cell death dose-dependently. It inhibited the generation of ${\cdot}O_2{^-}$, NO, $ONOO^-$ and $PGE^2$ in the $H_2O_2$-treated LLC-PK1 cells in vitro. PCR inhibited the espression of IKK-${\alpha}$, phospho-$I{\kappa}B-{\alpha}$, COX-2, iNOS, IL-$1{\beta}$ and VCAM-1 genes by means of decreasing the NF-${\kappa}B$ activation. These results suggest that PCR is an effective NO, ${\cdot}O_2{^-}$, $ONOO^-$ scavenger, and this substance recommended to be applied in treatment for the inflammatory process and inflammation-related disease.

• Natural Product Sciences
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• 제14권1호
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• pp.1-11
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• 2008

Peroxynitrite ($(ONOO^-)$ is a cytotoxic species formed from nitric oxide and superoxide anion, which are highly implicated in the pathogenesis of oxidative stress-mediated diseases. The aim of this study was to investigate the scavenging effects of Phellinus linteus on authentic $ONOO^-$, and further phytochemical studies are planned that will attempt to identify the active principles. From the active EtOAc fraction, a mixture of fungisterol and 5-dihydroergosterol (1), a mixture of betulin and 1,2-benzenedicarboxylic acid bis (2-methyl heptyl) ester (2), protocatechualdehyde (3), protocatechuic acid (4), cirsiumaldehyde (5), hispidin (6), caffeic acid (7), phelligridin D (8), uracil (9), gallic acid (10), 2,5-dihydroxybenzoic acid (11), ferulic acid (12), 2,3-dihydroxybenzaldehyde (13), arbutin (14), isoferulic acid (15), guanosine (16), and ellagic acid (17) were isolated, and their structures were characterized based on spectroscopic data. All compounds except 3, 6, 7 and 16 were isolated for the first time from P. linteus. Compounds 3, 4, 6-8, 10-15, and 17 showed potent scavenging activity on $ONOO^-$, with $IC_{50}$ values of $2.06\;{\pm}\;0.10$, $3.45\;{\pm}\;0.57$, $0.71\;{\pm}\;0.05$, $2.78\;{\pm}\;0.36$, $5.42\;{\pm}\;0.26$, $1.13\;{\pm}\;0.02$, $1.82\;{\pm}\;0.17$, $0.91\;{\pm}\;0.19$, $1.59\;{\pm}\;0.09$, $1.88\;{\pm}\;0.07$, $1.22\;{\pm}\;0.37$, and $2.01\;{\pm}\;0.02\;{\mu}M$, respectively, as compared to the positive control, DL-penicillamine, with an $IC_{50}$ value of $5.04\;{\pm}\;0.06\;{\mu}M$.