• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1220-1225
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• 2004

The overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is known to be responsible for vasodilation and hypotension observed in septic shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment of inflammatory diseases accompanied by overproduction of NO. In the course of screening oriental anti-inflammatory herbs for the inhibitory activity of NO synthesis, a crude methanolic extract of Curcuma zedoaria exhibited significant activity. The activity-guided fractionation and repetitive chromatographic procedures with the EtOAc soluble fraction allowed us to isolate three active compounds. They were identified as 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one (1), procurcumenol (2) and epiprocurcumenol (3) by spectral data analyses. Their concentrations for the 50% inhibition of NO production $(IC_{50})$ in lipopolysaccharide (LPS)-activated macrophages were 8, 75, 77 ${\mu}M$, respectively. Compound 1 showed the most potent inhibitory activity for NO production in LPS-activated macrophages, while the epimeric isomers, compound 2 and 3 showed weak and similar potency. Inhibition of NO synthesis by compound 1 was very weak when activated macrophages were treated with 1 after iNOS induction. In the immunoblot analysis, compound 1 suppressed the expression of iNOS in a dose-dependent manner. In summary, 1,7-bis (4-hydroxyphenyl)-1,4,6-heptatrien-3-one from Curcuma zedoaria inhibited NO production in LPS-activated macrophages through suppression of iNOS expression. These results imply that the traditional use of C. zedoaria rhizome as anti-inflammatory drug may be explained at least in part, by inhibition of NO production.

• Korean Journal of Acupuncture
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• v.22 no.4
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• pp.109-116
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• 2005

목적 : 골관절염은 진통을 수반하는 퇴행성 관절질환이며, 장애를 일으키는 주요한 원인이 된다. 또한 노인들에 있어서 골관절염은 매우 흔한 질환이라 할 수 있다. Nitric oxide(NO)는 Nitric Oxide Synthase(NOS)에 의하여 칼슘의존성통로를 통하여 L-arginine 으로부터 합성되어지며, NO는 중추신경계에 있어서 중요한 세포사이의 전달자이다. 방법 :본 연구에서는 위령선 으로부터 추출한 액이 콜라겐으로 유도된 관절염에 걸린 쥐의 dorsolateral periaqueductal gray(DL-PAG) 영역에서 nNOS(neuronal NOS)와 NOS에 대하여 미치는 영향 을 nNOS immunohistochemistry와 nicotinamide adenine dinucleotide phosphate-diaphorase(NADPH-d) 검사법을 통하여 조사하였다. 결과 : 골관절염이 유발된 흰쥐의 DL-PAG 영역에서 nNOS와 NOS의 발현억제가 관찰되었으며, 위령선이 콜라겐으로 유도된 골관절염에서 감소된 nNOS와 NOS의 발현이 증가되었다. 결론 : 본 연구를 통하여 위령선은 골관절염이 유발된 흰쥐의 DL-PAG에서의 nNOS와 NOS의 발현에 영향을 미친다는 결과를 얻을 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.539-545
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• 2016

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.

• Parasites, Hosts and Diseases
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• v.53 no.6
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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.

• Physical Therapy Korea
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• v.11 no.2
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• pp.47-63
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• 2004

In most tissues, apoptosis plays a pivotal role in normal development and in regulation of cell number. Therefore inappropriate apoptosis is revealed in a variety of diseases. This study was carried out to investigate the effects of acupuncture and needle electrode electrical stimulation on the change of caspase-3, 9 and neuronal nitric oxide synthase (nNOS) immunoreactive cells in the sprague dawley rats (SD rat). In immobilized SD rats (n=5), enhanced caspase-3 and caspase-9 expression were detected in the reticular part of substantia nigra, and enhanced nNOS was detected in the dorsolateral periaqueductal gray (DL-PAG) of midbrain and the paraventricular nucleus (PVN) of the hypothalamus using immunohistochemistry. Following the immobilization, acupuncture (n=5) and needle electrode electrical stimulation (n=5, 2 Hz) was applied at H$\acute{e}$g$\breve{u}$ (LI4) acupoint of SD rats, respectively. The stress-induced enhancement in the expression of caspase-3, 9 and nNOS were The present results demonstrate that and needle electrode electrical stimulation are effective in the modulation of expression of caspase-3, 9 and nNOS induced by immobilization.

• Herbal Formula Science
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• v.12 no.2
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• pp.163-173
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• 2004

Chelidonii Herba (CHE, Baek-gul-chae in Korean), which has its original description in Gu-Hwang-Bon-Cho, a classic book of oriental Herbal book, is widely used in the treatment of stomach cancer, jaundice, gasrtic ulcer, edema and stomach pain, in Korea, Japan and China. The present study was conducted to evaluate the effect of CHE on the nitric oxide (NO) production, iNOS and COX-2 expression in lipopolysaccharide - activated Raw 264.7 cells. After the treatment of CHE, NO production was monitored by measuring the nitrite content in culture medium, cell viability was measured by MIT assay. COX-2 and iNOS were determined by lmmunoblot analysis. The production of nitric oxide was significantly inhibited by pretreatment (1h) with CHE (0.1-0.3 mg／ml) on LPS-activated Raw264.7 cells. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein were up-regulated by LPS, but the increased levels of iNOS and COX-2 were inhibited by pretreatment of CHE (0.1-0.3 mg／ml), respectively. Thus, the present data suggest that CHE may play an important role in adjunctive therapy in Gram-negative bacterial infections.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.83-90
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• 2017

Advanced age is one of the risk factors for vascular diseases that are mainly caused by impaired nitric oxide (NO) production. It has been demonstrated that endothelial arginase constrains the activity of endothelial nitric oxide synthase (eNOS) and limits NO generation. Hence, arginase inhibition is suggested to be vasoprotective in aging. In this study, we examined the effects of intravenous injection of Piceatannol, an arginase inhibitor, on aged mice. Our results show that Piceatannol administration reduced the blood pressure in aged mice by inhibiting arginase activity, which was associated with NO production and reactive oxygen species generation. In addition, Piceatannol administration recovered $Ca^{2+}$/calmodulin-dependent protein kinase II phosphorylation, eNOS phosphorylation and eNOS dimer stability in the aged mice. The improved NO signaling was shown to be effective in attenuating the phenylephrine-dependent contractile response and in enhancing the acetylcholine-dependent vasorelaxation response in aortic rings from the aged mice. These data suggest Piceatannol as a potential treatment for vascular disease.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.297-302
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• 1997

Higenamine was widely used as traditional remedy for the treatment of rhumatoid arthritis. Nitric oxide(NO) may be a critical mediator in this inflammatory disease. Synovial tissue from humans with inflammatory arthritis expresses NOS2(iNOS) mRNA and protein, and generates NO in vitro. We therefore, investigated the effect of higenamine on the induction of nitric oxide synthase(NOS) promoted by lipopolysaccharide(LPS). Prophylactic application of higenamine selectively prevented LPS-primed initiation of L-arginine-induced relaxation and restored rhenylephrine(PE)-induced contraction in rat aorta. LPS-stimulated nitrite production in the incubation medium was reduced by higenamine. Furthermore, RT-PCR and Northern analysis indicated that higenamine reduced iNOS expression primed by LPS in rat aorta. These results suggest that higenamine prevents LPS-promoted induction of NOS in vascular smooth muscle.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.231-236
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• 2008

The current work was designed to assess novel pharmacological activities of 4-hydroxybenzaldehyde (HD), a major phenolic constituent of various natural products of plant origin, such as Gastrodia elata Blume. HD exhibited a significant inhibition in the chick chorioallantoic membrane (CAM) angiogenesis. HD also displayed an inhibitory effect in acetic acid-induced permeability in mice. Anti-nociceptive activity of HD was convinced using the acetic acid-induced writhing test in mice. HD was able to suppress production of nitric oxide (NO) and induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in the lipopolysaccharide (LPS)-activated RAW264.7 macrophages. HD also diminished the reactive oxygen species (ROS) level elevated in the LPS-activated macrophages. In brief, HD exhibits anti-angiogenic, anti-inflammatory and anti-nociceptive activities possibly via down-regulating iNOS and/or COX-2, which may be partly responsible for pharmacological efficacies of various natural products.

• Korean Journal of Medicinal Crop Science
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• v.15 no.5
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• pp.324-328
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• 2007

To search for immunoactive natural products exerting anti-inflammatory activity, we have evaluated the effects of the ethanol extracts of Rubus coreanus Miq. (ERC) on lipopolysaccharide-induced nitric oxide (NO), tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$, and $Interferon-{\gamma}\;(IFN-{\gamma})$ production by RAW 264.7 macrophage cell line. Our data indicate that this extract is a potent inhibitor of NO production and it also significantly decreased $IFN-{\gamma}\;and\;TNF-{\alpha}$ production. Consistent with these results, the protein level of inducible Nitric Oxide Synthase (iNOS) and cyclooxygenase-2 (COX-2) was inhibited by ethanol extracts of ERC in a dose-dependent manner. These results suggest that ERC may exert anti-inflammatory and analgesic effects possibly by suppressing the inducible NO synthase and COX-2 expressions.