• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.678-683
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• 2008

Aconitum pseudo-laeve var. erectum has traditionally been used for the treatment of water retention in the body. Administration of the aqueous extract of Aconitum pseudo-laeve var. erectum has the efficiency of anti-inflammatory activity and modulates the intestinal immune system. However, the mechanism of anti-inflammatory action of Aconitum pseudo-laeve var. erectum has not been clarified yet. In the present study, the effect of Aconitum pseudo-laeve var. erectum against LPS-stimulated expressions of COX-2 and iNOS 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), PGE2 immunoassay, and NO detection. The results of the present study indicate that Aconitum pseudo-laeve var. erectum is a potent inhibitor of the LPS-induced NO and $PGE_{2}$ production by blocking iNOS and $NF{\kappa}B$ activation in RAW 264.7 macrophages. These findings suggest that Aconitum pseudo-laeve var. erectum is a potential therapeutic for the treatment of inflammatory syndrome.

• Molecules and Cells
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• v.26 no.1
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• pp.48-52
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• 2008

We here demonstrate an anti-inflammatory action of raloxifene, a selective estrogen receptor modulator, in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells. Treatment with raloxifene at micromolar concentrations suppressed the production of nitric oxide (NO) by down-regulating expression of the inducible nitric oxide synthase (iNOS) gene in LPS-activated cells. The decreased expression of iNOS and subsequent reduction of NO were due to inhibition of nuclear translocation of transcription factor NF-${\kappa}B$. These effects were significantly inhibited by exposure to the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, LY294002, or by expression of a dominant negative mutant of PI 3-kinase. In addition, pretreatment with raloxifene reduced LPS-induced Akt phosphorylation as well as NF-${\kappa}B$ DNA binding activity and NF-${\kappa}B$-dependent reporter gene activity. Thus our findings indicate that raloxifene exerts its anti-inflammatory action in LPS-stimulated macrophages by blocking the PI 3-kinase-Akt-NF-${\kappa}B$ signaling cascade, and eventually reduces expression of pro-inflammatory genes such as iNOS.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.2
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• pp.123-129
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• 2009

Aprotinin is used clinically in cardiopulmonary bypass surgery to reduce transfusion requirements and the inflammatory response. The mechanism of action for the anti-inflammatory effects of aprotinin is still unclear. We examined our hypothesis whether inhibitory effects of aprotinin on cytokine-induced inducible nitric oxide synthase (iNOS) expression (IL-$l\beta$ plus TNF-$\alpha$), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-l induction in rat VSMCs. Aprotinin induced HO-l protein expression in a dose-dependent manner, which was potentiated during inflammatory condition. Aprotinin reduced cytokine mixture (CM)-induced iNOS expression in a dose dependent manner. Furthermore, aprotinin reduced CM-induced ROS generation, cell proliferation, and phosphorylation of JNK but not of P38 and ERK1/2 kinases. Aprotinin effects were reversed by pre-treatment with the HO-l inhibitor, tin protoporphyrin IX (SnPPIX). HO-l is therefore closely involved in inflammatory-stimulated VSMC proliferation through the regulation of ROS generation and JNK phosphorylation. Our results suggest a new molecular basis for aprotinin anti-inflammatory properties.

• The Journal of Korean Medicine
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• v.21 no.1
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• pp.91-98
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• 2000

The water extract of Seongpungtang(SPT) has commonly been used for treatment of ischemic brain damage in Oriental traditional medicine. However, little is known about the mechanism by which the water extract of SPT rescues brain cells from ischemic damage. To elucidate the protective mechanism of ischemic induced cytotoxicity, the regulation of Lipopolysaccharide (LPS) and PMA (phobol-12-myristate-13-acetate) induced iNOS expression in microglial cells was investigated. LPS and PMA treatment for 48 hr in microglial cells markedly induced nitric oxide (NO), but treatment of the cells with the water extract of SPT decreased nitrite formation. In addition, LPS and PMA treatment for 48 hr induced severe cell death in microglial cells. However treatment of the cells with the water extract of SPT did not induce significant changes compared to the control cells. Furthermore, NO production was markedly decreased by treatment of nuclear factor kappa B(NF-kB) inhibitor, pyrrolidine dithiocarbamate(PDTC). According to the above results, it is suggested that the protective effects of the water extract of SPT against ischemic brain damage may be mediated by regulation of iNOS during ischemic condition.

• Archives of Pharmacal Research
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• v.22 no.4
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• pp.410-413
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• 1999

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two $\beta$-carboline (2) have been isolated form the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 to 2 showed marked inhibitory activity of iNOS on LPS-and interferon-${\gamma}$-stimulated RAW 264.7 cells.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.210-215
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• 1999

Nitric oxide (NO) can mediate numerous physiological processes, including vasodilation, neurotransmission, cytotoxicity, secretion and inflammatory response. The regulation of NO production by inducible NO synthase (iNOS) is considered to be the possible target of the development of anti-inflammatory agent, based on the observation that NO can activate cyclooxygenase, which results in the synthesis of prostaglandins. In an effort to screen new inhibitor of NO production from about 352 species of herbal extracts, we found 9 species with 50% or more inhibitory effect on NO production. Especially, the dose-dependent inhibition of NO production in lipopolysaccharide-treated macrophages by two of the herbal extracts (Artemisiae asiaticae Herba and Saussureae Radix) was due to the decrease in the expression of iNOS.

• Archives of Pharmacal Research
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• v.27 no.1
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• pp.83-85
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• 2004

A sesquiterpene lactone, 1-O-acetyl-4R,6S-britannilactone (1) isolated from the flowers of Inula britannica L. var. chinensis (Rupr.) Reg. (Compositae), was found as an iNOS inhibitory constituent for the first time with an $IC_{50}$ value of 22.1 $\mu$ M which is more potent than the positive control, L-$N^6$-(1-iminoethyl)lysine ($IC_{50} =33.7 \mu$ M). Structure of compound 1 was identified by 1D and 2D NMR experiments and by comparison with the reference standard.

• Journal of Periodontal and Implant Science
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• v.43 no.2
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• pp.87-95
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• 2013

Purpose: The purpose of this study was to analyze the expression of inducible nitric oxide synthases (iNOS), tissue inhibitors of metalloproteinase $(TIMP)_{-3}$, and $TIMP_{-4}$ in the gingival tissues of periodontal patients with or without type 2 diabetes mellitus (DM). Methods: Depending on the patient's systemic condition and clinical criteria of the gingiva, each gingival sample was classified into one of three groups. Sixteen clinically, systemically healthy patients (group 1), 16 periodontal patients (group 2), and 16 periodontal patients with DM (group 3) were included. Tissue samples in each group were collected, prepared, and analyzed by western blotting. Quantification of the relative amount of $TIMP_{-3}$, $TIMP_{-4}$, and iNOS was performed. Results: The expression levels of iNOS and $TIMP_{-3}$ both increased in group 1, group 2, and group 3 in increasing order, and were significantly higher in both group 2 and group 3 as compared to group 1 (P<0.05). The expression levels of $TIMP_{-4}$ increased in the same order, but significantly increased in group 2 as compared to group 1, in group 3 as compared to group 1, and group 3 as compared to group 2 (P<0.05). Conclusions: This study demonstrated that iNOS, $TIMP_{-3}$, and $TIMP_{-4}$ might be involved in the progression of periodontal inflammation associated with type 2 DM. It is thought that further study of these factors can be applied practically for the diagnosis and control of periodontitis in diabetics.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.431-436
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• 2012

Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-${\gamma}$, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-${\gamma}$, but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-${\gamma}$-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.420-433
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• 1996

Background : There have been many debates about the effects of nitric oxide on the neurogenic inflammation. The role of nitric oxide in the neurogenic inflammation of airways will be required a better understanding of the localization and types of nitirc oxide synthase(NOS) activity in the neurogenic inflammation of airways. Method : To investigate the role of nitric oxide in airway neurogenic inflammation, 1) the effects of neurokinin receptor antagonist (FK224) and nitric oxide synthase inhibitor, $N^{\omega}$-nitro-L-arginine (L-NNA) on plasma extravastion were evaluated in four groups of Sprague-Dawley rats ; sham operation group(sham NANC group), electrical vagal stimulation group(NANC2 group), intravenous pretreatment groups with FK224 (1mg/kg ; FK224 group), and L-NNA(1mg/kg ; L-NNA group) 15 minutes before vagal NANC stimulation. 2) NOS activity in trachea with neurogenic inflammation was localized by immunohistochemical stain. Immunohistochemical stain was performed by antibodies specific for inflammatory cells(iNOS), brain(bNOS), and endothelium (eNOS) on trachea obtained from sham NANC, NANC2, and FK224 groups. Results : The results are that plasma extravsation in neurogenic inflammation of rat airways was inhibited by FK224, but enhanced by L-NNA pretreatment(P<0.05). There was significantly increased infiltration of inflammatory cells in subepithelium of neurogenic inflammatory trachea, but the reduction of subepithelial infiltration of inflammatory cells was observed after pretreatment with FK224(P<0.05). Immunostaining with anti-iNOS antibody showed strong reactivity only in infiltrated inflammatory cells in neurogenic rat trachea, and these iNOS reactivity was reduced by pretreatment with FK224. bNOS immunoreactivity was significantly increased only in the nerves both of neurogenic inflammatory and FK224 pretreated trachea compared with sham NANC trachea(p<0.05). eNOS immunoreactivity was not significant change in endothelium in neurogenic inflammation of rat trachea. Conclusion : These results suggest that nitric oxide released from iNOS in infiltrated inflammatory cells has main role in neurogenic inflammation of rat trachea. The presence of bNOS immunoreactivity in the nerves indicates that nitric oxide may be released from the nerves in rat trachea with neurogenic inflammation.