• Title/Summary/Keyword: Nitric oxide inhibition

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Inhibitory effects of Sam-Myo-San on the LPS-induced production of nitric oxide and $TNF-{\alpha}$ in RAW 264.7 cells and BV-2 Microglia cells (삼묘환(三妙丸)의 LPS에 의해 활성화된 RAW 264.7 cells과 BV-2 Microglia cells로부터 생성되는 nitric oxide 및 $TNF-{\alpha}$의 생성억제효과)

  • Lee, Jae-Hyun;Jung, Hyo-Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.21 no.4
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    • pp.59-67
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    • 2006
  • Objectives : Sam-Myo-Whan(SMW) has been known traditional prescription with anti- anthritis activities. We investigated inhibitory effects of SMW on lipopolysaccharide (LPS)-induced nitric oxide(NO), $TNF-{\alpha}$ and inducible nitric oxide synthase(iNOS) production from RAW264.7 cells and BV-2 Microglia cells. Methods : SMW, which had been extracted with 70% MeOH, concentrated and freeze-dried was used for this experiment. After BV2 mouse brain macrophages and RAW264.7 mouse peritoneal macrophages were pretreated with increasing concentrations of SMW extract for 30min, and then activated with LPS. To investigate cytotoxicity of SMW extract, cell viability was measured by MTT assay. NO production was measured in each culture supernatant by Griess reaction. mRNA expression of iNOS in two type cells was investigated by RT-PCR. $TNF-{\alpha}$ production was measured in each culture supernatant by ELISA. Results : SMW extract significantly inhibited LPS-induced NO and $TNF-{\alpha}$ production in BV2 cells and RAW264.7 cells dose-dependently. SMW extract also greatly suppressed mRNA expression of iNOS in both type cells activated with LPS. Conclusion : These data suggests that SMW extract may have an anti-inflammatory effect through the inhibition of iNOS expression.

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Effect of PAF Antagonists on the Nitric Oxide Synthesis in Ischemic Cerebral Cortex (PAF 길항제가 허혈성 대뇌 피질내 Nitric Oxide 합성에 미치는 영향)

  • No, Soon-Kee;Park, Kyu-Hyun;Lee, Won-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.6
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    • pp.665-672
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    • 1997
  • This study aimed to investigate the mechanism of cerebroprotection of platelet-activating factor(PAF) antagonists in transient cerebral ischemia of rat. Right middle cerebral artery(MCA) of Sprague-Dawley rat was occluded for 2 hours using an intraluminal filament technique. After 22 hours of reperfusion, morphometrically detectable infarct was developed in the cortex and striatum identical to the territory of MCA. The infarct size was significantly reduced by PAF antagonists, BN 52021 and CV-6209, as well as an inducible nitric oxide synthase(iNOS) inhibitor aminoguanidine(1 mg/kg, i.p., respectively) administered 5 min after MCA occlusion. PAF antagonists significantly inhibited the enzymatic activities of both myeloperoxidase and iNOS in the cerebral hemisphere ipsilateral to ischemia, whereas aminoguanidine did not inhibit myeloperoxidase activity but significantly inhibited the iNOS activity. These results suggest that PAF antagonists exert a cerebroprotective effect against ischemic brain damage through inhibition of leukocyte infiltration and iNOS activity in the postischemic brain.

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Anti-Inflammatory, Anti-Angiogenic and Anti-Nociceptive Activities of 4-Hydroxybenzaldehyde

  • Lim, Eun-Ju;Kang, Hyun-Jung;Jung, Hyun-Joo;Kim, Kyung-Hoon;Lim, Chang-Jin;Park, Eun-Hee
    • 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.

Independent Regulation of Endothelial Nitric Oxide Synthase by Src and Protein Kinase A in Mouse Aorta Endothelial Cells

  • Boo, Yong-Chool
    • Journal of Applied Biological Chemistry
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    • v.48 no.3
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    • pp.120-126
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    • 2005
  • Endothelial nitric oxide synthase (eNOS) plays a critical role in vascular biology and pathophysiology. Its activity is regulated by multiple mechanisms such as calcium/calmodulin, protein-protein interactions, sub-cellular locations and phosphorylation at various sites. Phosphorylation of eNOS-Ser1177 (based on mouse sequence) has been identified as an important mechanism of eNOS activation. However, signaling pathway leading to it phosphorylation remains controversial. The regulation of eNOS-Ser1177 phosphorylation by Src and protein kinase A (PKA) was investigated in the present study using cultured mouse aorta endothelial cells. Expression of a constitutively active Src mutant in the cells enhanced phosphorylation of eNOS and protein kinase B (Akt). The Src-stimulated phosphorylation was not attenuated by the expression of a dominant negative PKA regulatory subunit. Neither activation nor inhibition of PKA activity had any significant effect on tyrosine phosphorylation of activation or inactivation site in Src. Based on the results of this study, it is suggested that Src/Akt pathway and PKA signaling may regulate eNOS phosphorylation independently. The existence of multiple mechanisms for eNOS phosphorylation may guarantee endothelial nitric oxide production in various cellular contexts which is essential for maintenance of vascular health.

Anti-inflammatory and radical scavenging properties of Verbena officinalis

  • Shim, Hwan-Ki;Kim, Seong-Yeol;Kim, Bo-Rim;Cho, Jae-Park;Park, Yae-Jeong;Ji, Won-Geun;Cha, Dong-Seok;Jeon, Hoon
    • Advances in Traditional Medicine
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    • v.10 no.4
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    • pp.310-318
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    • 2010
  • Verbena officinalis (Verbenaceae) has been used as herbal medicine or health supplement in both Western and Eastern countries for centuries. In the present study, we examined the anti-inflammatory and antioxidant activities of the methylene chloride fraction of V. officinalis (VMC). To elucidate the anti-inflammatory properties of VMC, we investigated the inhibition effects of nitric oxide production in interferon-gamma (IFN-$\gamma$) and lipopolysaccharide-stimulated mouse peritoneal macrophages. VMC suppressed nitric oxide production, inducible nitric oxide synthase and cyclooxygenase-2 expression dose-dependently without notable cytotoxicity. In various radical scavenging assays, VMC exhibited strong scavenging effect on DPPH radical, superoxide radical, nitric oxide radical and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radical. VMC also showed potent reducing power. These findings strongly suggest that VMC may be beneficial in oxidative stress-mediated inflammatory disorders.

Effect of Gagam-Danguieumja through Regulation of MAPK on LPS-Induced Inflammation in RAW 264.7 Cells (LPS로 유도된 RAW 264.7 cell의 염증반응에서 MAPK 조절에 의한 가감당귀음자(加減當歸飮子)의 항염증 효과)

  • Kim, Tae-Yeon
    • The Journal of Internal Korean Medicine
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    • v.34 no.4
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    • pp.339-348
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    • 2013
  • Objectives : Danguieumja is a traditional medicinal prescription to treat skin disease. It was commonly used for the treatment of itching, chronic urticaria and atopic dermatitis in Korea by the addition or omission of several herbs. This study investigated the anti-inflammatory potential of Gagam-Danguieumja (GDE) water extract. Methods : We examined the effects of GDE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in a murine macrophage cell line, RAW 264.7 cells. Results : GDE inhibited production of NO in a dose dependent manner and also decreased the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2). As a possible molecular mechanism of anti-inflammatory effect increased phosphorylation of mitogen-activating protein kinases (MAPK) by LPS were blocked by GDE treatment. Conclusions : These results suggest that GDE has an anti-inflammatory therapeutic potential through the inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes.

Comparison of the Scrophulariae Radix of Gyeongbuk's with that of Chinese: Content of Harpagoside and Inhibitory Effect of Nitric Oxide (경북산 현삼과 중국산 현삼의 비교: Harpagoside 함량 및 Nitric Oxide 저해활성)

  • Zhang, Hai-Yan;Kim, Geum-Jin;Hwang, In-Hyun;Cho, Hi-Jae;Lee, Seung-Ho;Na, Min-Kyun
    • Korean Journal of Pharmacognosy
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    • v.42 no.1
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    • pp.15-21
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    • 2011
  • Scrophulariae Radix (Scrophulariaceae) has been traditionally used to treat pharyngitis, laryngitis, tonsillitis, fever, and edema. To compare the quality of the Scrophulariae Radix produced from Gyeongbuk with that from China, a quantitative analysis on the major component, E-harpagoside, was performed by reversed-phase HPLC, and a relative inhibitory activity of nitric oxide (NO) was assayed in the Raw 264.7 cells. Using a Luna $C_{18}$(2) column, we carried out quantitative analysis with a gradient of 0.1% phosphoric acid in water and acetonitrile. Our results demonstrated that the content of E-harpagoside in Gyeongbuk's Scrophulariae Radix were three times higher than that of Chinese. Moreover, the inhibitory activity of Scrophulariae Radix of Gyeongbuk's in the lipopolysaccharide (LPS)-induced NO production was higher than that of Chinese.

Luteolin and Chicoric Acid, Two Major Constituents of Dandelion Leaf, Inhibit Nitric Oxide and Lipid Peroxide Formation in Lipopolysaccharide-Stimulated RAW 264.7 Cells

  • Park, Chung-Mu;Park, Ji-Young;Song, Young-Sun
    • Preventive Nutrition and Food Science
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    • v.15 no.2
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    • pp.92-97
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    • 2010
  • Luteolin and chicoric acid are the most abundant phytochemicals in dandelion (Taraxacum officinale) leaf. In this study, four kinds of extraction methods [hot water, ambient temperature (AT) water, ethanol, and methanol] were applied to analyze the contents of both phytochemicals and verify their anti-inflammatory and antioxidative activities. The methanol extract showed the most potent nitric oxide (NO) inhibitory effect. The luteolin and chicoric acid concentrations were 3.42 and $12.86\;{\mu}g/g$ dandelion leaf in the methanol extract. The NO-suppressive effect of luteolin and chicoric acid was identified in a dose-dependent manner with $IC_{50}$ values of $21.2\;{\mu}M$ and $283.6\;{\mu}M$, respectively, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells without cytotoxicity. Malondialdehyde (MDA) concentration, as an index for free radical injury on cell membrane, was also dose-dependently inhibited by the two compounds. The suppressive effect was further examined using mRNA and protein expression levels, which were attributable to the inhibition of inducible nitric oxide synthase (iNOS). These results suggest that two phytochemicals in dandelion leaf, luteolin and chicoric acid, may play an important role in the amelioration of LPS-induced oxidative stress and inflammation.

Effects of Vitex rotundifolia on radical scavenging and nitric oxide production

  • Choi, Jae-Ki;Cha, Dong-Seok;Lee, Yong-Jae;Ko, Sung-Hoon;Park, Ho-Jun;Lee, Se-Yeoun;Choi, Jae-Hyuk;Jeon, Hoon
    • Advances in Traditional Medicine
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    • v.10 no.2
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    • pp.51-58
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    • 2010
  • Vitex rotundifolia (V. rotundifolia) has been used for treating headache, dizziness, toothache and removal of fever as a traditional medicine in Korea. In the present study, we examined the antioxidant and anti-inflammatory activities of 85% methanol extract of V. rotundifolia. In various radical scavenging assays, V. rotundifolia exhibited strong scavenging effect on 1, 1-diphenyl-2-picrylhydrazyl free radical, superoxide radical, nitric oxide. To elucidate the anti-inflammatory properties of V. rotundifolia, we investigated the inhibition effects of nitric oxide production in IFN-gamma and LPS-stimulated mouse peritoneal macrophages. V. rotundifolia suppressed nitric oxide production, iNOS and COX-2 expression dose-dependently through suppression of NF-$\hat{e}B$ activation without notable cytotoxicity. These findings mean that V. rotundifolia may be beneficial in oxidative stress-mediated inflammatory disorders.

Inhibition of Nitric Oxide Synthesis by Coumarins from Polygonum cuspidatum in LPS-Activated RAW 264.7 cells (호장근의 쿠마린에 의한 RAW 264.7 세포주의 nitric oxide 생성 저해활성)

  • Rho, Tae-Cheol;Choi, Hee-Cheol;Lee, Seung-Woong;Kim, Young-Ho;Rho, Mun-Chual;Kim, Young-Kook;Lee, Hyun-Sun
    • Korean Journal of Pharmacognosy
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    • v.32 no.3 s.126
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    • pp.181-188
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    • 2001
  • During the screening for inhibitors of nitric oxide production in LPS-activated macrophage, RAW 264.7 cells, two coumarins were isolated from chloroform extract of the root of Polygonum cuspidatum. They were identified as decursin (1) and decursinol angelate (2) on the basis of spectroscopic methods. The $IC_{50}$ values of these compounds on NO production were $0.76\;{\mu}M$ (1) and $2.6\;{\mu}M$ (2), respectively. However, the iNOS activity was not inhibited by treatment with these compounds. Their inhibitory effect on NO production seems to result from the suppression of iNOS induction through the suppression of NF-kB activity.

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