• 생약학회지
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• 제30권2호
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• pp.173-176
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• 1999

Bioassay-guided fractionation of a $H_2O$ extract of the roots of Gentiana scabra has furnished 5-(hydroxymethyl)-2-furfural (1) as an inhibitory compound for nitric oxide (NO) production in murine macrophage RAW 264.7 cells stimulated with $interferon-{\gamma}$ plus lipopolysaccharide. Compound 1 showed the moderate inhibition of NO production with $IC_{50}$ value of $803\;{\mu}M$.

• 약학회지
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• 제42권5호
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• pp.540-543
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• 1998

The nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase is known to be responsible for the vasodilation and hypotension observed in septic shock. We have found that 8-epi-xanthatin from Xanthium strumarium L. inhibited the production of NO in LPS-activated RAW 264.7 cells ($IC_{50}$ value was 1.5 ${\mu}$M). This activity was resulted from the suppressing of inducible nitric oxide synthase enzyme expression.

• 대한약리학회지
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• 제31권2호
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• pp.233-239
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• 1995

To verify the effect of immunosuppressants on the endotoxin-induced increase in iNOS activity, the action of immunosuppressants, dexamethasone (1.5 mg/kg), azathioprine (5 mg/kg/day) and cyclosporine (10 mg/kg), were evaluated in mice pretreated with LPS. The intraperitoneal injection of lipopolysaccharide (10 mg/kg) increased the nitric oxide synthase (NOS) activity in the brain and liver to maximum at 1 and 3 hours, respectively. The increase in NOS activity was blocked by the treatment with NOS inhibitor, LNAME(300 mg/kg) and aminoguanidine(100 mg/kg); a protein inhibitor, cycloheximide (10 mg/kg); and a transcription inhibitor of inducible NOS(iNOS), dexamethasone(1.5 mg/kg). Immunosuppressants, azathioprine (5 mg/kg) and cyclosporine (10 mg/kg), effectively blocked the increase in NOS activity. These results suggest that iNOS expression plays an important role in LPS-induced the increase in NOS activity and that immunosuppressants can be used as candidate for therapeutic agents in endotoxemia.

• Toxicological Research
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• 제11권2호
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• pp.303-308
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• 1995

Nitric oxide, a physiological transmitter, is reported to mediate cellular injury in various tissues. Its reactivity to free radical is believed to be one of the reasons for its involvement in cytotoxicity. Menadione, a representative quinone, is cytotoxic to several cell systems including isolated hepatocyte, endothelial cell and red blood cells. Its toxic mechanism is related to oxidative stress, mediated by toxic free radicals. Our previous studies demonstrated that menadione induced cell lysis and increase of oxygen consumption in platelets. It has been reported that platelets have nitric oxide producing enzyme, nitric oxide synthase. Thus, we have investigated to manifest the role of nitric oxide.in menadione-induced cytotoxicity in rat platelets. Menadione induced cytotoxicity in platelets was unaffected by $N^G$-nitro-arginine methyl ester (L-NAME), selective and competitive inhibitor of nitric oxide synthase. We also invesitgated the role of extracellular nitric oxide in menadione-induced cytotoxicity of platelets by addition with sodium nitroprusside (SNP). SNP did not affect platelet cytotoxicity by menadione. These results suggested that nitric oxide which was generated endogeneously or exogeneously might have a negligible role in menadione-induced cytotoxicity in rat platelets.

• The Korean Journal of Physiology and Pharmacology
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• 제8권3호
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• pp.161-165
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• 2004

Exogenous carbon monoxide (0.2%) increases L-type calcium $(Ca^{2+})$ current in human jejunal circular smooth muscle cells. The stimulatory effect of carbon monoxide (CO) on L-type $Ca^{2+}$ current is inhibited by pre-application of L-NNA, a classical competitive inhibitor of nitric oxide synthase (NOS) with no significant isoform selectivity (Lim, 2003). In the present study, we investigated which isoform of NOS affected CO induced stimulation of L-type $Ca^{2+}$ current in human jejunal circular smooth muscle cells. Cells were voltage clamped by whole-cell mode patch clamp technique, and membrane currents were recorded with 10 mM barium as the charge carrier. Before the addition of CO, cells were pretreated with each inhibitor of three NOS isoforms for 15 minutes. CO-stimulating effect on L-type $Ca^{2+}$ current was partially blocked by N-(3-(Amino-methyl) benzyl) acetamidine 2HCl (1400W, an iNOS inhibitor). On the other hand, 3-bromo-7-nitroindazole (BNI, a nNOS inhibitor) or $N^5-(1-Iminoethyl)-L-ornithine$ dihydrochloride (L-NIO, an eNOS inhibitor) completely blocked the CO effect. These data suggest that low dose of exogenous CO may stimulate all NOS isoforms to increase L-type $Ca^{2+}$ channel through nitric oxide (NO) pathway in human jejunal circular smooth muscle cells.

• 대한간호학회지
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• 제41권4호
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• pp.520-527
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• 2011

Purpose: The purpose of this study was to examine effects of nitric oxide synthase (NOS) inhibitor on muscle weight and myofibrillar protein content of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. Methods: Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The NOSI group (n=19) had NOS inhibitor (L-NAME) injections daily for 14 days, and the Vehicle group (n=20) had vehicle injections daily for 14 days. Withdrawal threshold, body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from hindlimbs. Muscle weight and myofibrillar protein content of the dissected muscles were determined. Results: The NOSI group showed significant increases as compared to the Vehicle group for body weight at 15 days, muscle weight and myofibrillar protein content of the unaffected soleus and gastrocnemius. The NOSI group demonstrated a higher pain threshold than the vehicle group. Conclusion: NOSI for 14 days attenuates unaffected soleus and gastrocnemius muscle atrophy in neuropathic pain model.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.511-519
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• 1998

This study investigated the role of nitric oxide on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion and its relation to mucus. Nitric oxide synthesis modulators such as L-arginine and $N^G-nitro-L-arginine$ methyl ester, and sodium nitroprusside, a nitric oxide donor, were injected intraperitoneally to the rats 30 min prior to ischemia/reperfusion which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. Lipid peroxide production, the contents of glutathione and mucus, and glutathione peroxidase activities of gastric mucosa were determined. Histological observation of gastric mucosa was performed by using hematoxylin-eosin staining and scanning electron microscopy. The result showed that ischemia/reperfusion increased lipid peroxide production and decreased the contents of glutathione and mucus as well as glutathione peroxidase activities of gastric mucosa. Ischemia/reperfusion induced gastric erosion and gross epithelial disruption of gastric mucosa. Pretreatment of L-arginine, a substrate for nitric oxide synthase, and sodium nitroprusside prevented ischemia/reperfusion-induced alterations of gastric mucosa. However, $N^G-nitro-$ L- arginine methyl ester, a nitric oxide synthase inhibitor, deteriorated oxidative damage induced by ischemia/reperfusion. In conclusion, nitric oxide has an antioxidant defensive role on gastric mucosa by maintaining mucus, glutathione, and glutathione peroxidase of gastric mucosa.

• 약학회지
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• 제45권1호
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• pp.16-22
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• 2001

Novel yakuchinone derivatives have been designed, synthesized and evaluated their inhibitory activity of NO production in lipopolysaccharide (LPS)-activated macrophages. From this study, some enone compounds have been found to be highly active in the assay. In view of the importance of NO in septic shock and inflammation, these compounds may be useful candidates for the development of new drug to treat endotoxemia and inflammation accompanying overproduction of NO.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.673-679
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• 1997

It has been generally accepted that glutamate mediates the ischemic brain damage, excitotoxicity, and induces release of neurotransmitters, including norepinephrine(NE), in ischemic milieu. In the present study, the role of nitric oxide(NO) in the ischemia-induced $[^3H]norepinephrine([^3H]NE)$ release from cortex slices of the rat was examined. Ischemia, deprivation of oxygen and glucose from $Mg^{2+}-free$ artificial cerebrospinal fluid, induced significant release of $[^3H]NE$ from cortex slices. This ischemia-induced $[^3H]NE$ release was significantly attenuated by glutamatergic neurotransmission modifiers. $N^G-nitro-L-arginine$ methyl ester(L-NAME), $N^G-monomethyl-L-arginine$ (L-NMMA) or 7-nitroindazole, nitric oxide synthase inhibitors attenuated the ischemia-evoked $[^3H]NE$ release. Hemoglobin, a NO chelator, and 5, 5- dimethyl-L-pyrroline-N-oxide(DMPO), an electron spin trap, inhibited $[^3H]NE$ release dose-dependently. Ischemia-evoked $[^3H]NE$ release was inhibited by methylene blue, a soluble guanylate cyclase inhibitor, and potentiated by 8-bromo-cGMP, a cell permeable cGMP analog, zaprinast, a cGMP phosphodiesterase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide generator. These results suggest that the ischemia-evoked $[^3H]NE$ release is mediated by NMDA receptors, and activation of NO system is involved.

• The Korean Journal of Physiology and Pharmacology
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• 제7권5호
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• pp.283-287
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• 2003

While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.