• Archives of Pharmacal Research
• /
• v.27 no.12
• /
• pp.1233-1237
• /
• 2004

The effects of four tanshinones isolated from Tanshen (the root of Salvia miltiorrhiza Bunge, Labiatae) were tested for their inhibition of nitric oxide production in macrophage cells, and the underlying molecular mechanisms studied. Of the four tanshinones used, 15, 16-dihydrotanshinone- I, tanshinone-IIA and cryptotanshinone, but not tanshinone I, demonstrated significant inhibition of the LPS-induced nitric oxide production in RAW 264.7 cells, with calculated $IC_{50}$ values of 5, 8, and 1.5 ${\mu}M$ , respectively. Tanshinones exerted inhibitory activities on the LPS-induced nitric oxide production only when applied concurrently with LPS, and tanshinone- IIA and cryptotanshinone were found to inhibit LPS-induced NF-$_KB$ mobilization and extracellular- regulated kinase (ERK) activation, respectively. These results suggest that tanshinones inhibit LPS-induced nitric oxide generation by interfering with the initial stage of LPS-induced expression of certain genes. NF-$_KB$ and ERK could be the molecular targets for tanshinones for the inhibition of LPS-induced nitric oxide production in macrophage cells.

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

• Journal of the korean Society of Automotive Engineers
• /
• v.7 no.3
• /
• pp.83-93
• /
• 1985

The prediction of emission concentrations in a 4cycle spark ignition engine was made by considering nonuniform model with thermodynamics, chemical equilibrium and kinetic mechanism of nitric oxide. Calculation of this model shows that a temperature difference of the order of 500K can be established across he cylinder. Results of the kinetic calculation of nitric oxide show that the temperature gradient across the cylinder has a profound effect on the nitric oxide formation. The predicted values for nitric oxide, carbon dioxide and carbon monoxide agree with measured ones for a variety of equivalence ratio.

• The Korean Journal of Pharmacology
• /
• v.32 no.3
• /
• pp.389-397
• /
• 1996

Gatric mucosa is exposed to toxic, reactive oxygen species generated within the lumen. Nitric oxide protected acetaminophen-induced hepatotoxicity by maintaining glutathione homeostasis. The present study examined the role of nitric oxide in mediating hydrogen peroxide - induced damage to gastric cells. Hydrogen peroxide was generated by glucose oxidase acting on ${\beta}-D-glucose$. L-arginine, $N^G-nitro-L-arginine$ methyl ester, or $N^G-nitro-L-arginine$ were treated to the cells with glucose/glucose oxidase. Lipid peroxidation and nitrite release and cellular content of glutathione were determined. As a result, dose - dependent increase in lipid peroxide production as well as dose - dependent decrease in nitrite release and cellular glutathione content were observed in glucose/glucose oxidase - treated cells. Pretreatment of L-arginine, a substrate for nitric oxide synthase, prevented the increase of lipid peroxide production and the reduction of nitrite release as well as glutathione content. Inhibitors of nitric oxide synthase such as $N^G-nitro-L-arginine$ methyl ester and $N^G-nitro-L-arginine$ did not protect hydrogen peroxide - induced cell damage. In conclusion, nitric oxide protects gestric cells from hydrogen peroxide possibly by inhibiting lipid peroxidation and by preserving cellular glutathione stores.

• The Korean Journal of Physiology and Pharmacology
• /
• v.2 no.2
• /
• pp.233-239
• /
• 1998

Stimulated alveolar macrophages and neutrophils produce nitric oxide, a free radical by an inducible nitric oxide synthase(iNOS), which reacts with superoxide anion to form peroxynitrite, a more highly reactive toxic species. The objectives of the present study were to evaluate acute inflammatory lung injury and to determine iNOS mRNA induction and nitric oxide production by rat broncho-alveolar lavage cells following intratracheal treatment of silica. After 4 h exposure to silica, differential counts of broncho-alveolar lavage cells and lactate dehydrogenase(LDH) activity as well as total protein in the broncho-alveolar lavage fluid were determined. Broncho-alveolar lavage cells were also assayed for iNOS mRNA and the productions of nitrite and nitrate measured in the cells cultured. Differential analysis of broncho-alveolar lavage cells showed that the number of alveolar macrophages slightly decreased following silica treatment; however, red blood cells, lymphocytes, and neutrophils significantly were increased by 9-, 14-, and 119-fold following silica treatment, respectively, compared with the saline control. It was also found significant increases in the LDH activity and total protein in the lavage fluid obtained from silica-treated rats, indicating silica-induced acute lung injury. Northern blot analysis demonstrated that the steady state levels of iNOS mRNA in broncho-alveolar lavage cells were increased following silica treatment. The productions of nitrite and nitrate in the cultured cells were significantly increased by 2-fold following silica treatment, respectively, which were attenuated by the NOS inhibitor $N{\omega}-nitro-L-arginine-methyl$ ester(L-NAME) and partially reversed by L-arginine. These findings suggest that nitric oxide production in alveolar macrophages and recruited neutrophils is increased in response to silica. Nitric oxide may contribute in part to acute inflammatory lung injury.

• The Korean Journal of Physiology and Pharmacology
• /
• v.4 no.3
• /
• pp.263-270
• /
• 2000

To evaluate the involvement of nitric oxide production on the endothelium-dependent relaxation in diabetes, we have measured vascular and endothelial function and nitric oxide concentration, and the expression level of endothelial nitric oxide synthase in the streptozotocin-induced diabetic rats. Diabetic rats were induced by the injection of streptozotocin (50 mg/kg i.v.) in the Sprague-Dawley rats. Vasoconstrictor responses to norepinephrine (NE) showed that maximal contraction to norepinephrine $(10^{-5}\;M)$ was significantly enhanced in the aorta of diabetic rats. Endothelium-dependent relaxation induced by acetylcholine was markedly impaired in the aorta of diabetic rats, these responses were little improved by the pretreatment with indomethacin. However, endothelium-independent relaxation induced by nitroprusside was not altered in the diabetic rats. Plasma nitrite and nitrate $(NO_2/_3)$ levels in diabetic rats were significantly lower than in non-diabetic rats. Western blot analysis using a monoclonal antibody against endothelial cell nitric oxide synthase (eNOS) revealed that the protein level was lower in the aorta of diabetic rats than in non-diabetic rats. These data indicate that nitric oxide formation and eNOS expression is reduced in diabetes, and this would, in part, account for the impaired endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1995.04a
• /
• pp.41-44
• /
• 1995

• Environmental Mutagens and Carcinogens
• /
• v.22 no.3
• /
• pp.183-186
• /
• 2002

Hypertension is a multifactorial disease. Both genetic and environmental factors have been implicated in its etiology. Since the impairment of nitric oxide (NOS) production plays an important role in the pathogenesis of hypertension, endothelial nitric oxide synthase (ecNOS) gene is supposed to be a candidate gene of hypertension. Our study group investigated the 27 bp insertion/deletion (Ins/Del) polymorphism of ecNOS gene in 99 Korean normotensives and 98 hypertensives, respectively. There was no significant association with any cardiovascular risk factors as well as hypertension in Koreans. The Ins/Del polymorphism of the ecNOS gene indicated the similar allele distribution among ethnic groups studied. Further studies using larger sample size and subject information is required to describe the general picture of the association between the ecNOS gene polymorphic loci and hypertension

• Biomolecules & Therapeutics
• /
• v.18 no.4
• /
• pp.351-362
• /
• 2010

Nitric oxide (NO), synthesized from L-arginine by three isoforms of NO synthase (NOS), is a gaseous signaling molecule with an astonishingly wide range of biological and pathophysiological activities, including vasorelaxation, angiogenesis, anti-inflammation, and anti-apoptosis in mammalian cells. Recent studies have shown that NO donors and inhaled NO convert to biologically active NO under biological conditions and act as a signaling molecule in pathophysiological conditions. This review will discuss the roles of NO and its potential therapeutic implication in various human diseases, such as tumor, vascular regeneration, hypertension, wound healing, and ischemia-reperfusion injury.

• The Journal of Korean Medicine
• /
• v.26 no.4
• /
• pp.152-161
• /
• 2005

The excessive release of proinflammatory products by activated microglia causes neurotoxicity, and this has been implicated in the pathogenesis of neurodegenerative diseases. Harpagophytum procumbens (Pedaliaceae) has been widely used for the treatment of pain and arthritis in the clinical field. In this study, we investigated the effect of Harpagophytum procumbens against lipopolysaccharide-induced inflammation. From the present results, the aqueous extract of Harpagophytum procumbens was shown to suppress prostaglandin-E2 synthesis and nitric oxide production by inhibiting the lipopolysaccharide-stimulated enhancement of cyclooxygenase-2 and inducible nitric oxide synthase expressions in mouse BV2 microglial cells. These results suggest that Harpagophytum procumbens may offer a valuable means of therapy for the treatment of brain inflammatory diseases by attenuating lipopolysaccharide-induced prostaglandin-E2 synthesis and nitric oxide production.