• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.183-187
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• 2001

Nitric oxide (NO) produced in large amounts by the inducible nitric oxide synthase (iNOS) is known to be responsible for the vasodilation and hypotension observed in septic shock and inflammation. The 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 Chinese medicinal plants and screened their inhibitory activity against NO production in lipopolysaccharide (LPS)-activated macrophages. Among the 80 kinds of extracts of herbal drugs, 15 extracts showed potent inhibitory activity of NO production above 80% at the concentration o$50\mu\textrm{g}/ml$. These potent extracts showed dose dependent inhibition of NO production of LPS-activated macrophages at the concentration of 50, 30,$10\mu\textrm{g}/ml$. Especially, Rhus chinensis, Senecio scandens and Wikstroemia indica showed most potent inhibition above 50% at the concentration of $10\mu\textrm{g}/ml$. These plants are promising candidates for the study of the activity-guided purification of active compounds and would be useful for the treatment of inflammatory diseases and endotoxemia accompanying the overproduction of NO.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.159-164
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• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• Journal of Animal Science and Technology
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• v.60 no.1
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• pp.2.1-2.5
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• 2018

Infectious Bursal Disease is a severe viral disease of chicken responsible for serious economic losses to poultry farmers. The causative agent, Infectious Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian ginseng, Withania somnifera, inhibits Infectious Bursal Disease virus in vitro. Also, Withania somnifera root extract is known to induce nitric oxide production in vitro. Therefore, the present study was undertaken to determine if the inhibitory activity of Withania somnifera against Infectious Bursal Disease virus was based on the production of nitric oxide. We show that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide. Our results also highlight the paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal Disease.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.74-78
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• 1999

Nine sesquiterpene lactones, which were isolated from Hemisteptia lyrata Bunge, Chrysanthemum zawadskii Herbich var. latilobum Kitamura and Chrysanthemum boreale Makino were evaluated for the inhibition upon the nitric oxide release from the Raw cell and for the ACAT (acyl Co A: cholesterol acyltransferase) inhibitory assay. In the nitric oxide release inhibitory experiment, hemistepsin B $(IC_{50}\;=\;0.05\;{\mu}g/ml,\;0.15\;{\mu}M),$ cumambrin B, tulipinolide and costunolide exhibited strong inhibition with $IC_{50}$ values $0.05\;{\mu}g/ml\;(0.15\;{\mu}M),\;0.1\;{\mu}g/ml\;(0.38\;{\mu}M),\;0.2\;{\mu}g/ml\;(0.69\;{\mu}M)$ and $0.2\;{\mu}g/ml(0.86\;{\mu}M),$ respectively. In the ACAT inhibitory assay, angeloylcumambrin B, tigloylcumambrin B, tulipinolide and costunolide exhibited strong inhibition with $IC_{50}$ values $33\;{\mu}g/ml\;(95.4\;{\mu}M),\;22\;{\mu}g/ml\;(63.6\;{\mu}M),\;38\;{\mu}g/ml\;(151\;{\mu}M)$ and $17\;{\mu}g/ml(73.3\;{\mu}M),$ respectively, whereas other compounds did not exhibit significant activity against ACAT above $100\; {\mu}g/ml.$.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.123-128
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• 2011

Caesalpinia sappan (C. sappan) is a medicinal plant used for promoting blood circulation and removing stasis. During a screening procedure on medicinal plants, the ethylacetate extract of the lignum of C. sappan (CLE) showed inhibitory activity on arginase which has recently been reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. CLE inhibited arginase II activity prepared from kidney lysate in a dose-dependent manner. In HUVECs, inhibition of arginase activity by CLE reciprocally increased NOx production through enhancement of eNOS dimer stability without any significant changes in the protein levels of eNOS and arginase II expression. Furthermore, CLE-dependent arginase inhibition resulted in increase of NO generation and decrease of superoxide production on endothelium of isolated mice aorta. These results indicate that CLE augments NO production on endothelium through inhibition of arginase activity, and may imply their usefulness for the treatment of cardiovascular diseases associated with endothelial dysfunction.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.2
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• pp.54-70
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• 2008

Background and Object : This study was carried out to investigate the effects of GCSBPT (Gagam-Cheongsang BangPungTang) on the in vitro and in vivo anti-inflammatory reactions. Methods : Vascular permeability and Cyclooxygenase inhibition assay are examined in vitro and nitric oxide inhibition assay, radical scavenging activity test, $TNF-{\alpha}$, COX-2 inhibition test are examined in vivo. Results : GCSBPT showed inhibitory effects on vascular permeability and leukocyte migration in animal test. In cyclooxygenase 2 inhibition assay, an ethanol extract of GCSBPT inhibited prostaglandin E2 generation at a concentration of $10{\mu}g/ml$. Among the herbal ingredients of GCSBPT, ethanol extracts of Nepetae Spica exhibited potent inhibitory activities. Ethanol extract of GCSBPT inhibited the release of nitric oxide and the gene expression of inducible nitric oxide synthase in RAW 246.7 cells stimulated by lipopolysaccharide. Ethanol extract of GCSBPT exhibited radical scavenging activity of 54% at $100{\mu}g/ml$. Among the herbal ingredients of GCSBPT. Conclusions : According to the above results, I expected that GCSBPT was a potent anti-inflammatory prescription.

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.134.2-135
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• 2001

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.441-447
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• 2016

Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (${\alpha}_2$-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of $10^{-8}{\sim}10^{-6}mol/L$, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or $3{\times}10^{-9}mmol/L$) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial ${\alpha}_2$-adrenoceptor and nitric oxide synthase.

• The Korea Journal of Herbology
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• v.22 no.2
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• pp.73-78
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• 2007

Objectives : Uncontrolled activation of microglia may directly toxic to neurons by releasing various substances such as inflammatory cytokines, nitric oxide(NO), prostaglandin E2 and superoxide. In this study, the effects of the several subfractions isolated from Coptidis Rhizoma extract were investigated on NO production in LPS-stimulated BV2 microglial cells, Methods : Coptidis Rhizoma extract prepared with 80% methanol, and then fractionated with ethylacetate, chloroform, n-butanol and water. BV2 cells were pretreated four subfractions of Coptidis Rhizoma with various concentrations, and then stimulated with LPS. Cytotoxicity of each fraction was measured by MTT assay. NO production was determined in culture surpernatants by Griess reagent. Results : Ethylacetate, chloroform and butanol fractions of Coptidis Rhizoma extract significantly decreased LPS-induced NO production in BV2 cells as a dose-dependent manner without cytotoxicity. Ethylacetate fraction of Coptidis Rhizoma extract was most effective on inhibition of NO production in LPS-stimulated BV2 cells compared with other fractions. Conclusion : This data indicates that Ethylacetate fraction of Coptidis Rhizoma extract shows strong antiinflammatory effects through inhibition of LPS-induced microglial activation.

• Archives of Pharmacal Research
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• v.27 no.9
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• pp.937-943
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• 2004

Recent investigations have shown that certain flavonoids, especially flavone derivatives, inhibit nitric oxide (NO) production by inducible NO synthase (iNOS) in macrophages, which contrib-ute their anti-inflammatory action. For the purpose of finding the optimized chemical structures of flavonoids that inhibit NO production, various A- and B-ring substituted flavones were syn-thesized and evaluated for their inhibitory activity using lipopolysaccharide-treated RAW 264.7 cells. It was found that the optimal chemical structures were A-ring 5,7-dihydroxyflavones hav-ing the B-ring 2＇,3＇-dihydroxy or 3＇,4＇-dihydroxy or 3＇,4＇-hydroxy/methoxy (methoxy/hydroxy) groups. These structurally optimized compounds were revealed to be down-regulators of iNOS induction, but not direct iNOS inhibitors. Of these derivatives that were evaluated, 2＇,3＇,5,7-tet-rahydroxyflavone and 3＇,4＇,5,7-tetrahydroxyflavone (Iuteolin) showed the strongest inhibition. The $IC_{50}$/ values for these compounds were 19.7 and 17.1 11M, respectively. Therefore, these compounds may have a potential as new anti-inflammatory agents.