• Parasites, Hosts and Diseases
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• 제53권6호
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• pp.777-783
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• 2015

The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.203.2-204
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• 2003

Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidate for the treatment of inflammatory diseases accompanied by the overproduction of NO. We prepared alcoholic extracts of woody plants and screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages after the treatment of these extracts. (omitted)

• 생명과학회지
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• 제16권2호
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• pp.192-198
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• 2006

본 연구에서는 DEP의 노출이 새로운 호흡기계 질환 유발의 가능성과 호흡기계의 염증성인자로 잘 알려진 lipopolysaccharide (LPS)의 역할에 어떠한 영향을 미치는 지를 확인하고자 폐에서 염증성 반응 시 생성이 증가하는 것으로 알려진 Nitric Oxide (NO)의 형성과 NO의 생성에 관련된 효소인 inducible nitric oxide synthase (iNOS) 및 NO에 의하여 형성되는 것으로 알려진 nitrotyrosilated-protein을 폐포 대식세포를 통해 분석하였다. 폐포대식세포에 DEP를 농도 별로 단독 처리하였을 때와 동일한 농도에서 배양시간을 달리하였을 때는 NO가 생성되지 않았으나 DEP와 함께 LPS를 처리하였을 때는 LPS를 단독으로 처리했을 때보다. 유의성이 있게 증가함을 확인할 수 있었다. 또한 NO의 생성에 관련된 효소인 iNOS 및 NO에 의하여 형성되는 것으로 알려진 nitrotyrosilated-protein 발현의 정도를 면역화학염색과 Western analysis로 확인할 수 있었다. DEP는 폐포대식세포에서 직접적으로 NO생성에 영향을 미치지 않았으며, NO를 생성하는 iNOS나 nitrotyrosilated-protein의 발현에도 영향을 주지 않았으나 세균성 염증인자의 한 종류인 LPS가 NO를 형성하는 데에는 통계학적인 상승효과가 있었다. 결론적으로 본 연구에서는 염증성질환의 환자에서 DEP의 흡입은 간접적으로 NO를 형성하는데 영향을 미쳐 질환을 악화시킬 것으로 판단한다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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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)

• 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.145-145
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• 1998

In the present study, we have demonstrated that taurine could stimulate the production of nitric oxide and the activity of ERK2 (extracellular signal regulated protein kinase or pp42 MAP kinase). Nitric oxide(NO), the product of inducible nitric oxide synthase(iNOS), is known to be implicated in the metabolism of bone. ERK cascade plays a key role in the gene expression of iNOS in osteoblastic cell. We investigated whether taurine (l-20mM) could stimulate ERK2 activity, nitric oxide production, and inducible nitric oxide synthase in osteoblast-like UMR-106 cells. Nitric oxide was measured spectophotometrically as nitrite and the activation of ERK2 and iNOS was studied using Western 145 blot analysis. Taurine increased the production of nitric oxide in a dose-dependent manner and the effect was reached to a maximum at 10 mM. The activation of iNOS were consistent with NO levels. The tyrosine phosphorylation of ERK2 was increased by taurine in a time-dependent manner. The these result suggest that taurine might stimulate the production of nitric oxide in osteoblast-like cells by the activation of ERK2 and could regulate the metabolism of bone via nitric oxide.

• 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.293.2-293.2
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• 2002

Bisphenol A ［BPA. 2.2-bis(4-hydroxyphenyl)propane］ is reported to have estrogenic activity: however. its influence on cytokine production or immune system function remains unclear. In this study. we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a), and on the level of inducible nitric oxide synthase (iNOS) and TNF-a gene expression in mouse macrophages. BPA alone did not affect NO or TNF-a production. (omitted)

• Archives of Pharmacal Research
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• 제26권10호
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• pp.832-839
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• 2003

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and produce excessive amounts of nitric oxide (NO) and prostaglandin E$_2$ (PGE$_2$), which play key roles in the processes of inflammation and carcinogenesis. The root of Paeonia lactiflora Pall., and the root cortex of Paeonia suffruticosa Andr., are important Chinese crude drugs used in many traditional prescriptions. 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) is a major bioactive constituent of both crude drugs. PGG has been shown to possess potent anti-oxidant, anti-mutagenic, anti-proliferative and anti-invasive effects. In this study, we examined the inhibitory effects of 1,2,3,4,6-penta-O-galloyl-$\beta$-D-glucose (PGG) isolated from the root of Paeonia lactiflora Pall. on the COX-2 and iNOS activity in LPS-activated Raw 264.7 cells, COX-1 in HEL cells. To investigate the structure-activity relationships of gallate and gallic acid for the inhibition of iNOS and COX-2 activity, we also examined (-)-epigallocatechin gallate (EGCG), gallic acid, and gallacetophenone. The results of the present study indicated that PGG, EGCG, and gallacetophenone treatment except gallic acid significantly inhibited LPS-induced NO production in LPS-activated macrophages. All of the four compounds significantly inhibited COX-2 activity in LPS-activated macrophages. Among the four compounds examined, PGG revealed the most potent in both iNOS ($IC_{50}$ = 18 $\mu\textrm{g}/mL$) and COX-2 inhibitory activity (PGE$_2$: $IC_{50}$ = 8 $\mu\textrm{g}/mL$ and PGD$_2$: $IC_{50}$ = 12 $\mu\textrm{g}/mL$), respectively. Although further studies are needed to elucidate the molecular mechanisms and structure-activity relationship by which PGG exerts its inhibitory actions, our results suggest that PGG might be a candidate for developing anti-inflammatory and cancer chemopreventive agents.

• 한국식품영양과학회지
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• 제38권12호
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• pp.1685-1690
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• 2009

본 연구에서는 구절초의 항염증 효과를 탐색하기 위해 NO의 함량과 iNOS의 발현 및 PGE2와 COX-2의 발현을 LPS로 염증을 유도한 RAW 264.7 macrophage cell을 이용하여 실험하였다. 연구 결과 구절초 꽃 추출물은 NO 함량을 농도 의존적으로 감소시키는 경향을 나타냈으며 유의한 차이를 보였다. 또한 세포독성은 꽃 추출물(5～50 μg/mL)은 최고 농도인 50 μg/mL에서 약 20%의 독성을 나타냈으며 그 이하의 농도에서는 독성을 나타내지 않았다. NO 생성의 억제는 iNOS의 단백질과 mRNA의 발현을 농도 의존적으로 저해하였으며 유의성 있는 차이를 나타내었다. 이 결과로 구절초 꽃 추출물이 전사단계에서 저해 활성을 나타낸다는 것을 보여주었다. 그러나 PGE2와 COX-2의 발현 억제 효과는 나타나지 않았으며, 이 결과 구절초 꽃 추출물에 의한 COX-2 단백질의 발현 억제와 PGE2 생성 억제는 유의성이 없는 것으로 나타났다. 본 연구 결과, 구절초 추출물은 염증을 일으키는 중요 인자인 NO를 저해하였고, iNOS의 발현, iNOS의 mRNA 발현 등 항염증에 우수한 효과를 보였으며, 항염증 연구의 기초 자료로 활용될 것으로 예상된다. 또한 추후 산업적 응용도 가능하므로 지속적인 연구가 진행되어야 할 것으로 사료된다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.101-101
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• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

• Preventive Nutrition and Food Science
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• 제13권4호
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• pp.362-365
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• 2008

Agaricus bisporus, also known as white button mushroom, is one of the most popular mushrooms consumed in Korea. This mushroom contains high concentrations of flavanoids and exhibits antioxidant activity. In this study, we examined the effects of Agaricus bisporus ethanol extract (ABE) on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein levels were assessed in cells treated with $100\;{\mu}M$ LPS in the presence or absence of ABE. 0.5 mg/mL of ABE suppressed NO production significantly. Moreover, ABE inhibited levels of iNOS protein. Taken together, these results suggest that ABE exerts anti-inflammatory activity in LPS-induced inflammation in RAW 264.7 cells.