• 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.

• Nutritional Sciences
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• 제7권4호
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• pp.214-217
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• 2004

Dietary intervention and simvastatin is beneficial in the prevention cardiovascular diseases by lowering plasma lipid levels. Endothelial dysfunction is associated with coronary artery disease and its risk factors and is reversed by dietary intervention. It has been suggested that hyperlipidemia contributes to the development of atherosclerosis by increasing inducible nitric oxide synthase (iNOS) expression via intimal thickening. Statins treatment has been found to decrease iNOS expression and atherogenensis in animal models. We hypothesized that dietary intervention and simvastatin therapy could decrease plasma nitric oxide in hypercholesterolemic patients, which would suggest the opportunity for modulation of iNOS expression through the use of statins in a clinical situation. We measured the plasma levels of nitrite and nitrate (NOx) in 19 hyperlipidemia patients. The subjects were under dietary intervention following simvastatin therapy for 12 weeks. As a result, the plasma level of NOx, stable metabolites of nitric oxide (NO), saw a two-fold elevation in hyperlipidemic patients as compared to normal levels. Although 12 weeks of dietary intervention did not lower NOx levels, subsequent 12-week simvastatin (10 mg/day) treatment, along with dietary intervention, lowered NOx levels significantly. This NOx reduction, induced by simvastatin therapy, positively correlated with lowered coronary risk factors (r=0.40, p=0.02). It indicated that simvastatin therapy decreases plasma NOx levels by, perhaps, decreasing iNOS expression or activity leading to the attenuation of the development of neointima.

• 대한한의학회지
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• 제23권2호
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• pp.19-27
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• 2002

Objective : This study was designed to investigate the effect of Hyeolbuchukeo-tang (HCT) on NO production and the molecular mechanism of NO production modulated by HCT in the primary VSMC (vascular smooth muscle cells). Method : Primary VSMC was established from aorta and cultured VSMC used in this study. NO production of VSMC was assayed by Griess reagent and the expression of iNOS gene was assayed by Western, RT-PCR. Result : $TNF-{\gamma}$ induced NO production, but $IFN-{\gamma}$ or HCT alone did not induce NO production in cultured VSMC. However, $IFN-{\gamma}$ or HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC in a time- and dose-dependent manner. $TNF-{\gamma}$ induced the iNOS gene expression corresponding to NO production in $TNF-{\gamma}-treated$ VSMC. HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC by about 20%, but HCT did not increase the level of iNOS mRNA in $TNF-{\gamma}-treated$ VSMC. HCT slightly increased the level of iNOS protein in $TNF-{\gamma}-treated$ VSMC. Calcium ionophore A23187 decreased NO production in $TNF-{\gamma}-treated$ VSMC, but HCT attenuated the effect of A23187. Conclusion : As NO is deeply involved in the development of arteriosclerosis and dilation of blood vessels, drugs or chemicals modulating NO production in VSMC could be used for preventing and treating arteriosclerosis. Considering the effect of HCT on the modulation of NO production in VSMC, MCT has a potential capacity for preventing and treating diseases of the circulation system including arteriosclerosis.

• Fisheries and Aquatic Sciences
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• 제14권4호
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• pp.275-282
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• 2011

Inflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been implicated in various inflammatory diseases. In this study, we investigated the anti-inflammatory activities of Chondria crassicaulis ethanolic extract (CCE) by measuring its effects on the expression of iNOS and COX-2 proteins in lipopolysaccharide (LPS)-treated RAW 264.7 murine macrophages. CCE significantly and dose-dependently inhibited the LPS-induced release of nitric oxide and prostaglandin $E_2$, and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells, without causing any cytotoxicity. It also inhibited the production of the pro-inflammatory cytokines such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$ in LPS-stimulated RAW 264.7 cells. Moreover, treatment with CCE strongly suppressed nuclear factor-${\kappa}B$ (NF-${\kappa}B$) promoter-driven expression in LPS-treated RAW 264.7 cells. CCE treatment blocked nuclear translocation of the p65 subunit of NF-${\kappa}B$ by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that CCE regulates iNOS and COX-2 expression through NF-${\kappa}B$-dependent transcriptional control, and identifies potential candidates for the treatment or prevention of inflammatory diseases.

• 생약학회지
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• 제39권2호
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• pp.95-103
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• 2008

In the present study, we investigated the anti-inflammatory effects by kaempferol-3-O-${\beta}$-D-sophoroside (KS) isolated from Sophora japonica (Leguminosae) on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin ($PGE_2$) production by RAW 264.7 cell line compared with kaempferol. KS significantly inhibited the LPS-induced NO and $PGE_2$ production. Consistent with these observations, KS reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner. In addition, the release and the mRNA expression levels of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-6 (IL-6) were also reduced by KS. Moreover, KS attenuated the LPS-induced activation of nuclear factor-kappa B ($NF{-\kappa}B$), a transcription factor necessary for pro-inflammatory mediators, iNOS, COX-2, $TNF-{\alpha}$ and IL-6 expression. These results suggest that the down regulation of iNOS, COX-2, $TNF-{\alpha}$, and IL-6 expression by KS are achieved by the downregulation of $NF{-\kappa}B$ activity, and that is also responsible for its anti-inflammatory effects.

• 동의생리병리학회지
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• 제19권3호
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• pp.785-791
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• 2005

Corydalis Tuber has traditionally been used for the treatment of water retention in the body. Administration of the aqueous extract of Corydalis Tuber has been known to be effective for the control of pain and treatment of arthritis. It was reported that Corydalis Tuber possesses anti-inflammatory activity and modulates the intestinal immune system. The effect of Corydalis Tuber against LPS-stimulated expressions of COX-2, iNOS, and $IL-1{\beta}$ in cells of the murine RAW 264.7 macrophages was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcription-polymerase chain reaction (RT-PCR), $PGE_2$ immunoassay, and NO detection. The aqueous extract of Corydalis Tuber was shown to suppress $PGE_2$ production by inhibition on the LPS-stimulated enhancement of COX-2 enzyme activity, $IL-1{\beta}$, and iNOS expression in the RAW 264.7 macrophages. Present results suggest that Corydalis Tuber exerts anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ expressions, resulting in inhibition of $PGE_2$ synthesis. Corydalis Tuber has anti-inflammatory and analgesic effects probably by suppressing of COX-2, iNOS, and $IL-1{\beta}$ mRNA expressions, resulting in inhibition of $PGE_2$ and NO synthesis.

• 동의생리병리학회지
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• 제20권3호
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• pp.603-608
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• 2006

In activated macrophage, large amounts of nitric oxide (NO) are generated by inducible nitric oxide synthase (iNOS), resulting in acute or chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, water extracts from the fruit of Chaenomeles sinensis, the root of Polygonum cuspidatum and Boswellia carterii inhibited the LPS-induced NO production in a parallel dose-dependent manner. To investigate the mechanism by which those extracts inhibits NO production, we examined the expression of iNOS and COX-2 in both mRNA and protein levels. We observed a significant change in the iNOS expression between LPS alone and LPS plus those extracts-treated cells. However, water extracts from Chaenomeles sinensis, Polygonum cuspidatum and Boswellia carterii did not inhibit COX-2 expression which was induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis, Polygonum cuspidatum and Boswellia carterii can modulate anti-inflammatory immune response, which may be in part associated with the regulation of NO synthesis through the regulation of iNOS expression in mouse macrophage cells.

• 동의생리병리학회지
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• 제31권4호
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• pp.220-225
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• 2017

Lithospermi Radix (LR) is known to have an anti-inflammatory effect. However, the mechanisms are not well known. In this study, LPS-induced mouse RAW 264.7 macrophage cells were treated with LR to investigate the time-dependent inflammation response of LR. RAW 264.7 cells were treated with various concentrations of LR for 24 hours, followed by MTS assay. Cell viability was increased at all experimental concentrations. The mRNA expression levels of $IL-1{\beta}$, $TNF-{\alpha}$ and iNOS were increased by treatment of RAW 264.7 cells with LR at a concentration of $200{\mu}g/ml$ for 6 hours and 24 hours. Treatment of LR with $200{\mu}g/ml$ concentration for 6 hours promoted mRNA expression levels of $IL-1{\beta}$, $TNF-{\alpha}$ and iNOS in LPS-induced RAW 264.7 cells. However, $IL-1{\beta}$, $TNF-{\alpha}$ and iNOS mRNA expression was suppressed by treatment of LR with $200{\mu}g/ml$ concentration for 24 hours in LPS-induced RAW 264.7 cells. These results suggest that the effect on inflammation of LR is promptly promoted and then to rapidly alleviate the inflammatory reaction. This study proposes that the time-dependent activities of herbal medicine is a very important factor in analyzing the anti-inflammatory effect of various herbal medicines including LR.

• 한방재활의학과학회지
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• 제23권2호
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• pp.33-48
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• 2013

Objectives : Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficits. Sukjiyanggeun-Tang(shudiyangjin-tang), in oriental medicine, has been used to treat various musculoskeletal disorders. Methods : In the present study, the effects of aqueous extract of Sukjiyanggeun-Tang(shudiyangjin-tang) on functional recovery, severity of pain, and expressions of neurofilament, cycloxygenease-2(COX-2), inducible nitric oxide synthase(iNOS), and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) following sciatic crushed nerve injury in rats were investigated. For this study, walking tract analysis, plantar test, western blot analysis for COX-2 iNOS, and TNF-${\alpha}$, and Immunofluorescence test for neurofilament were performed. Results : In the present results, sciatic functional index(SFI) in walking tract analysis was significantly decreased following sciatic crushed nerve injury, and pain severity in plantar test was significantly increased. COX-2, iNOS and TNF-${\alpha}$ expressions were increased whereas neurofilament expression was decreased by sciatic crushed nerve injury, In contrast, treatment with Sukjiyanggeun-Tang(shudiyangjin-tang) improved SFI in walking tract analysis and suppressed the pain severity in sciatic crushed nerve injury. Sukjiyanggeun-Tang(shudiyangjin-tang) treatment also suppressed COX-2, iNOS, and TNF-${\alpha}$ expressions and enhanced the neurofilament expression in sciatic crushed nerve injury. Conclusions : In the present study, we have shown that Sukjiyanggeun-Tang(shudiyangjin-tang) is the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.

• 한방안이비인후피부과학회지
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• 제33권1호
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• pp.1-11
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• 2020

Objectives : The purpose of this study was to investigate the anti-inflammatory and anti-oxidative effects of Osung-tang(OST) extract. Methods : MTT assay was performed to confirm the survival rate of RAW 264.7 cells treated with OST extract(50-400㎍/㎖) and the production of NO from LPS-induced RAW 264.7 cells was confirmed. The mRNA expression of iNOS, COX-2, and NF-κB were measured by real-time PCR. The protein expression of iNOS, COX-2 and p-IκB were measured by western blot and the anti-oxidant activity of OST extract(50-400㎍/㎖) was investigated by measuring DPPH scavenging activity. Results : OST extract showed a cell survival rate of 90% or more at 50-400㎍/㎖. The NO production was inhibited in a dose-dependent manner in RAW 264.7 cells treated with LPS on OST treated group. mRNA expression levels of iNOS, COX-2 and NF-κB decreased in a concentration-dependent manner after treatment with OST(50-400㎍/㎖). Protein expression levels of iNOS, COX-2 and p-IκB decreased in a concentration-dependent manner after treatment with OST(50-400㎍/㎖). It was found that OST has a high free-radical scavenging ability. Conclusions : These results suggest that OST extract can be used as a treatment for various skin diseases by demonstrating its anti-inflammatory and anti-oxidant effects.