• Title/Summary/Keyword: Inducible NO synthase

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Inhibitors of Inducible Nitric Oxide Synthase Expression from Artemisia iwayomogi

  • Ahn, Hanna;Kim, Ji-Yeon;Lee, Hwa-Jin;Kim, Yong-Kyun;Ryu, Jae-Ha
    • Archives of Pharmacal Research
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    • v.26 no.4
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    • pp.301-305
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    • 2003
  • Nitric oxide (NO) is an important bioactive agent that mediates a wide variety of physiological and pathophysiological events. NO overproduction by inducible nitric oxide synthase (iNOS) results in severe hypotension and inflammation. This investigation is part of a study to discover new iNOS inhibitors from medicinal plants using a macrophage cell culture system. Two sesquiterpenes (1 and 2) were isolated from Artemisia iwayomogi (Compositae) and were found to inhibit NO synthesis ($IC_{50} 3.64 \mu g/mL and 2.81 \mu$g/mL, respectively) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Their structures were identified as 3-Ο-methyl-iso-secotanapartholide (1) and iso-secotanapartholide (2). Compounds 1 and 2 inhibited the LPS-induced expression of the iNOS enzyme in the RAW 264.7 cells. The inhibition of NO production via the down regulation of iNOS expression may substantially modulate the inflammatory responses.

Upregulation of Nitric Oxide Synthase Activity by All-trans Retinoic Acid and 13-cis Retinoic Acid in Human Malignant Keratinocytes

  • Moon, Ki-Young
    • Biomedical Science Letters
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    • v.25 no.2
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    • pp.196-200
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    • 2019
  • Effect of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, on the activity of nitric oxide synthase (NOS) was evaluated in human malignant keratinocytes to examine the possible correlation of retinoids with NOS activities. All-trans retinoic acid and 13-cis retinoic acid did not alter the nitric oxide (NO) production. However, in the presence of lipopolysaccharide (LPS, $1{\mu}g/mL$), they significantly increased NO release in a dose-dependent manner until 48 h at concentrations of $50{\sim}100{\mu}M$. The degree of upregulation of NO by all-trans retinoic acid and 13-cis retinoic acid increased up to 35% and 37%, respectively, compared to that by the control, which demonstrated the upregulation of LPS-inducible nitric oxide synthase (iNOS)-dependent generation of NO as well as showing a crucial link between retinoids-induced activity and NOS. Findings of this study now suggest that the upregulation of LPS-iNOS activity may be associated with modulation of retinoids-induced control of cellular developmental processes, which may produce new therapeutics of retinoids in the complexity of how NO affects human keratinocytes.

Anti-inflammatory effect of Distylium racemosum leaf biorenovate extract in LPS-stimulated RAW 264.7 macrophages cells (LPS로 유도된 RAW 264.7 세포에 대한 조록나무 잎 Biorenovation 추출물의 항염증 활성)

  • Hong, Hyehyun;Lee, Kyung-Mi;Park, Taejin;Chi, Won-Jae;Kim, Seung-Young
    • Journal of Applied Biological Chemistry
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    • v.64 no.4
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    • pp.375-382
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    • 2021
  • Biorenovation is a microbial enzyme-based structural modification of component compounds in natural products and synthetic compounds including plant extracts with the potential benefits of improved biological activities compared with its reaction substrates. In this study, we investigated the anti-inflammatory activity of Distylium racemosum leaf extract and D. racemosum leaf biorenovation extract (DLB). As a result, DLB inhibited nitric oxide, prostaglandin E2, and inflammatory cytokines including tumor necrosis factor-α, interleukin-6, interleukin-1β at non-toxic concentrations. In addition, DLB significantly inhibited inducible nitric oxide synthase and cyclooxygenase-2 on LPS-treated RAW 264.7 macrophages. Based on these results, we suggest that the DLB could be used as a potent anti-inflammatory agents. It also suggests that the application of biological evolution has potential usefulness to increase the practical value of natural products.

Puerariae flos inhibits inflammatory responses in interferon-γ and lipopolysaccharide-stimulated mouse peritoneal macrophages

  • Hong, Seung-Heon;Kim, Hong-Joon;Cha, Dong-Seok;Lee, Ju-Young;Na, Ho-Jeong
    • Advances in Traditional Medicine
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    • v.7 no.3
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    • pp.229-234
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    • 2007
  • In macrophages, nitric oxide (NO) is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions including inflammation. In this study, we have examined the inhibition effects of NO production by 85% methanol extract of the flower of Pueraria thunbergiana (PF) in mouse macrophages. Extract of PF (1, 10, 100 ${\mu}g/ml$) inhibited NO production, inducible NO synthase and cyclooxygenase-2 expression in interferon-g and lipopolysaccharide-stimulated mouse peritoneal macrophages and it had no cytotoxicity. These data suggest that 85% methanol extract of PF might be useful in controlling macrophages mediated inflammatory disease.

Inhibitory Effect of a Sesquiterpene from Artemisia iwayomogi on Expression of Inducible Nitric Oxide Synthase by Suppression of I-κBα Degradation in LPS-stimulated RAW 264.7 Cells

  • Kim, Na Yeon;Koh, Hye Jin;Li, Hua;Lee, Hwa Jin;Ryu, Jae-Ha
    • Natural Product Sciences
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    • v.23 no.2
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    • pp.92-96
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    • 2017
  • A sesquiterpene was purified from Artemisia iwayomogi methanolic extract during the course of searching anti-inflammatory principle from medicinal plants. A sesquiterpene identified as armefolin inhibited the production of nitric oxide (NO) and attenuated inducible nitric oxide synthase (iNOS) protein level in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Armefolin also down-regulated mRNA expressions of iNOS and pro-inflammatory cytokines, interleukin-$1{\beta}$ and interleukin-6 in LPS-activated macrophages. Moreover, armefolin suppressed the degradation of inhibitory-${\kappa}B{\alpha}$ (I-${\kappa}B{\alpha}$) in LPS-activated macrophages. These data suggest that armefolin from A. iwayomogi can suppress the LPS-induced production of NO and the expression of iNOS gene through inhibiting the degradation of I-${\kappa}B{\alpha}$. Taken together, armefolin from A. iwayomogi might be a candidate as promising anti-inflammatory agent.

Inhibition of Inducible Nitric Oxide Synthase by Agaricus bisporus Extract in RAW 264.7 Macrophages

  • Ahn, Ji-Yun;Lee, Hyun-Jung;Moon, Mi-Kyung;Kim, Su-Na;Ha, Tae-Youl
    • Preventive Nutrition and Food Science
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    • v.13 no.4
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    • pp.362-365
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    • 2008
  • Agaricus bisporus, also known as white button mushroom, is one of the most popular mushrooms consumed in Korea. This mushroom contains high concentrations of flavanoids and exhibits antioxidant activity. In this study, we examined the effects of Agaricus bisporus ethanol extract (ABE) on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 cells. Nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) protein levels were assessed in cells treated with $100\;{\mu}M$ LPS in the presence or absence of ABE. 0.5 mg/mL of ABE suppressed NO production significantly. Moreover, ABE inhibited levels of iNOS protein. Taken together, these results suggest that ABE exerts anti-inflammatory activity in LPS-induced inflammation in RAW 264.7 cells.

Inhibitory Effect of Galangin from Alpinia officinarum on Lipopolysaccharide-induced Nitric Oxide Synthesis in RAW 264.7 macrophages (고량강으로부터 분리된 galangin의 RAW 264.7 세포주에서 LPS로 유도된 nitric oxide 생성 저해활성)

  • Lee, Hwa Jin
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.511-515
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    • 2014
  • In a screen for plant-derived inhibitors of nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells, a flavonol isolated from the chloroform extract of Alpinia officinarum was isolated. The structure of the flavonol was found to be 3,5,7-trihydroxy-2-phenylchromen-4-one (galangin, GLG) by using spectroscopy. GLG exhibited an inhibitory effect ($IC_{50}$ value: $26.8{\mu}M$) on NO production in LPS-stimulated RAW 264.7 murine macrophage cells. Moreover, GLG suppressed expressions of inducible nitric oxide synthase (iNOS) protein and mRNA in a dose-dependent manner.

Inhibitory Effect of Panax notoginseng on Nitric Oxide Synthase, Cyclo-oxygenase-2 and Neutrophil Functions

  • Park, Soon-Gi;Joo, Shin-Tak;Ban, Chang-Gyu;Moon, Jin-Young;Park, Sun-Dong;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1295-1302
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    • 2006
  • Our preliminary aim is to elucidate the pharmacokinetic features of the PNS(Panax notoginseng Buck F.H. Chen. (Arialiaceae) root). First, we assessed the prevention of neurtrophil functions. A Panax notoginseng inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. This Panax notoginseng reduced nitric oxide (NO) and prostaglandin E2 production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. Panax notoginseng significantly reduced mouse paw oedema induced by carrageenan. The results indicate that Panax notoginseng exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.

The Effects of Diesel Exhaust Particles on the Alveolar Macrophages for Inducible Nitric Oxide Synthase Induction and Nitric Oxide with Nitrotyrosilated-protein Formation (디젤분진이 폐포대식세포에서 nitric oxide의 생성과 inducible nitric oxide synthase의 발현 및 nitrotyrosilated-protein의 형성에 미치는 효과)

  • Lim Young;Choe Myung-Ok;Lee Kweon-Haeng;Kim Kyung-A;Kim Kil-Soo;Lee Myoung-Heon;Li Tian-Zhu;Lee Soo-Jin;Choe Nong-Hoon
    • Journal of Life Science
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    • v.16 no.2 s.75
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    • pp.192-198
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    • 2006
  • Epidemiological studies have demonstrated an association between exposure to diesel exhaust particles (DEP) and adverse cardiopulmonary effects. Despite the epidemiological proof, the pathogenesis of DEP-related pulmonary diseases remain poorly understood. So, comprehensive in vivo and in vitro researches are required to know the effects of DEP on diverse lung diseases. Alveolar macrophages (AM) and airway epithelial cells are known as important cellular targets in DEP-induced lung diseases. Other studies have shown that nitric oxide (NO) is involved in particle matter induced lung injury. The present study was undertaken to determine whether DEP has an synergistic effects on lipopolysaccharide (LPS)-induced NO formation and inducible nitric oxide synthase (iNOS) with nitrotyrosilated-protein formation in cultured primary alveolar macrophages. The formation of NO was determined through the Griess reaction in the cultured medium and iNOS with nitrotyrosilated-proteins are analyzed by immunohistochemical staining and Western analysis. The results indicate that DEP exposure does not induce NO formation by itself, however DEP showed significant synergistic effects on LPS-induced NO formation. So, our results suggest that DEP inhalation could aggravate inflammatory lung disease through NO formation.

Suppressive Effects of Chrysanthemum zawadskii var. latilobum Flower Extracts on Nitric Oxide Production and Inducible Nitric Oxide Synthase Expression (구절초 꽃 추출물의 Nitric Oxide 생성과 Inducible Nitric Oxide Synthase 발현 억제 효과)

  • Han, Ji-Young;Kim, Young-Hwa;Sung, Jee-Hye;Um, Yu-Rry;Lee, Yi;Lee, Jun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.12
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    • pp.1685-1690
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    • 2009
  • In this study, we investigated the effect of C. zawadskii extract on nitric oxide (NO) production, prostaglandin E2 (PGE2) production, protein and mRNA expression of inducible nitric oxide synthase (iNOS) in LPS-induced RAW 264.7 macrophage cells. C. zawadskii extract (5~50 μg/mL) significantly inhibited LPS-induced NO production in a concentration-dependent manner ranging from 23.3% to 100%. Consistent with the inhibitory effect on NO production, C. zawadskii extract inhibited the protein expression and mRNA expression of iNOS. Although flower extracts of C. zawadskii was not effective on the expression of PGE2 and COX-2, flower extracts of C. zawadskii, however, showed a strong anti-inflammatory activity through inhibition of NO production and iNOS expression. The present results suggest that C. zawadskii extract has an inhibitory effect on NO production, and thus can be used as an anti-inflammatory agent.