scholarly journals Methanol Extract ofArtemisia apiaceaHance Attenuates the Expression of Inflammatory Mediators via NF-κB Inactivation

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Ji Choul Ryu ◽  
Sang Mi Park ◽  
Min Hwangbo ◽  
Sung Hui Byun ◽  
Sae Kwang Ku ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Potential ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Paw Edema ◽  
Concentration Dependent Manner ◽  
Proinflammatory Mediators ◽  
Inducible Nitric Oxide

Artemisia apiaceaHance is one of the most widely used herbs for the treatment of malaria, jaundice, and dyspeptic complaint in oriental medicine. This study investigated the effects of methanol extracts ofA. apiaceaHance (MEAH) on the induction of inducible nitric oxide synthase (iNOS) and proinflammatory mediators by lipopolysaccharide (LPS) in Raw264.7 macrophage cells and also evaluated thein vivoeffect of MEAH on carrageenan-induced paw edema in rats. MEAH treatment in Raw264.7 cells significantly decreased LPS-inducible nitric oxide production and the expression of iNOS in a concentration-dependent manner, while MEAH (up to 100 μg/mL) had no cytotoxic activity. Results from immunoblot analyses and ELISA revealed that MEAH significantly inhibited the expression of cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in LPS-activated cells. As a plausible molecular mechanism, increased degradation and phosphorylation of inhibitory-κBαand nuclear factor-κB accumulation in the nucleus by LPS were partly blocked by MEAH treatment. Finally, MEAH treatment decreased the carrageenan-induced formation of paw edema and infiltration of inflammatory cells in rats. These results demonstrate that MEAH has an anti-inflammatory therapeutic potential that may result from the inhibition of nuclear factor-κB activation, subsequently decreasing the expression of proinflammatory mediators.

Tetrahydrobiopterin synthesis and inducible nitric oxide production in pulmonary artery smooth muscle

1994 ◽  
Vol 266 (4) ◽  
pp. L455-L460 ◽  
Author(s):  
D. K. Nakayama ◽  
D. A. Geller ◽  
M. Di Silvio ◽  
G. Bloomgarden ◽  
P. Davies ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
De Novo ◽  
Interleukin 1 ◽  
No Production ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Pulmonary Artery Smooth Muscle ◽  
Inducible Nitric Oxide

We recently reported (Am. J. Respir. Cell Mol. Biol. 7: 471-476, 1992) that a mixture of lipopolysaccharide (LPS) and cytokines produced a time-dependent increase in mRNA and protein expression of inducible nitric oxide synthase (iNOS) in cultured rat pulmonary artery smooth muscle cells (RPASM). In the current study we extend observations on regulation of iNOS in RPASM by showing that de novo synthesis of tetrahydrobiopterin (BH4) is critical for LPS and cytokine-induced NO production. A mixture of LPS and the cytokines gamma-interferon, interleukin-1 beta, and tumor necrosis factor-alpha increased steady-state levels of mRNA of GTP-cyclohydrolase-I (GTP-CH), the rate-limiting enzyme in BH4 biosynthesis. Levels of mRNA to GTP-CH became detectable by 4 h, with further increases at 24 h by Northern blot analysis and reverse-transcriptase polymerase chain reaction. Total intracellular biopterin levels, undetectable under basal conditions, increased after 24 h exposure to LPS and cytokines (to 32.3 +/- 0.8 pmol/mg protein). LPS and cytokine-induced NO production, determined by nitrite concentrations in the medium, was decreased in a concentration-dependent manner by the GTP-CH inhibitor, 2,4-diamino-6-hydroxypyrimidine (DAHP) at 24 h. DAHP also inhibited completely the LPS- and cytokine-induced accumulation of intracellular biopterins. Sepiapterin, which supplies BH4 through a salvage pathway independent of GTP-CH, reversed the effect of DAHP on LPS and cytokine-induced NO production.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Coptis chinensisand Myrobalan (Terminalia chebula) Can Synergistically Inhibit Inflammatory Response In Vitro and In Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Enhui Cui ◽  
Xiaoyan Zhi ◽  
Ying Chen ◽  
Yuanyuan Gao ◽  
Yunpeng Fan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Potential ◽  
In Vitro Cytotoxicity ◽  
High Dose ◽  
Dependent Manner ◽  
Paw Edema ◽  
Coptis Chinensis ◽  
Anti Inflammatory

Objectives. To investigate the anti-inflammatory effect ofCoptis chinensisplus myrobalan (CM) in vitro and in vivo.Methods. The inflammation in mouse peritoneal macrophages was induced by lipopolysaccharide (LPS). Animal models were established by using ear swelling and paw edema of mouse induced by xylene and formaldehyde, respectively. In vitro, cytotoxicity, the phagocytosis of macrophages, the levels of nitric oxide (NO), induced nitric oxide synthase (iNOS), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) in cell supernatant were detected. In vivo, swelling rate and edema inhibitory rate of ear and paw were observed using CM-treated mice.Results. At 150–18.75 μg·mL−1, CM had no cytotoxicity and could significantly promote the growth and the phagocytosis of macrophages and inhibit the overproduction of NO, iNOS, TNF-α, and IL-6 in macrophages induced by LPS. In vivo, pretreatment with CM, the ear swelling, and paw edema of mice could be significantly inhibited in a dose-dependent manner, and the antiedema effect of CM at high dose was better than dexamethasone.Conclusion. Our results demonstrated thatCoptis chinensisand myrobalan possessed synergistically anti-inflammatory activities in vitro and in vivo, which indicated that CM had therapeutic potential for the prevention and treatment of inflammation-mediated diseases.

scholarly journals Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

2000 ◽  
Vol 68 (12) ◽  
pp. 7087-7093 ◽  
Author(s):  
Y.-H. Li ◽  
Z.-Q. Yan ◽  
J. Skov Jensen ◽  
K. Tullus ◽  
A. Brauner
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Alveolar Macrophages ◽  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

scholarly journals Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial V̇o2 during exercise

2012 ◽  
Vol 303 (1) ◽  
pp. R94-R100 ◽  
Author(s):  
Robert Boushel ◽  
Teresa Fuentes ◽  
Ylva Hellsten ◽  
Bengt Saltin
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Mitochondrial Respiration ◽  
Complex I ◽  
Ex Vivo ◽  
Knee Extension ◽  
Physiological Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner

Nitric oxide (NO) and prostaglandins (PG) together play a role in regulating blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome- c oxidase. Indomethacin uncouples and inhibits the electron transport chain in a concentration-dependent manner, and thus, inhibition of NO and PG synthesis may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG synthesis blockade (l-NMMA and indomethacin, respectively) on mitochondrial respiration in human muscle following knee extension exercise (KEE). Specifically, this study examined the physiological effect of NO, and the pharmacological effect of indomethacin, on muscle mitochondrial function. Consistent with their mechanism of action, we hypothesized that inhibition of nitric oxide synthase (NOS) and PG synthesis would have opposite effects on muscle mitochondrial respiration. Mitochondrial respiration was measured ex vivo by high-resolution respirometry in saponin-permeabilized fibers following 6 min KEE in control (CON; n = 8), arterial infusion of NG-monomethyl-l-arginine (l-NMMA; n = 4) and Indo ( n = 4) followed by combined inhibition of NOS and PG synthesis (l-NMMA + Indo, n = 8). ADP-stimulated state 3 respiration (OXPHOS) with substrates for complex I (glutamate, malate) was reduced 50% by Indo. State 3 O2 flux with complex I and II substrates was reduced less with both Indo (20%) and l-NMMA + Indo (15%) compared with CON. The results indicate that indomethacin reduces state 3 mitochondrial respiration primarily at complex I of the respiratory chain, while blockade of NOS by l-NMMA counteracts the inhibition by Indo. This effect on muscle mitochondria, in concert with a reduction of blood flow accounts for in vivo changes in muscle O2 consumption during combined blockade of NOS and PG synthesis.

scholarly journals Endothelium-Dependent Vasorelaxant Effect of Butanolic Fraction fromCaryocar brasilienseCamb. Leaves in Rat Thoracic Aorta

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Lais Moraes de Oliveira ◽  
Aline Gabriela Rodrigues ◽  
Elaine Fernanda da Silva ◽  
Letícia Bonancio Cerqueira ◽  
Carlos Henrique Castro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dependent Manner ◽  
Native Plant ◽  
Concentration Dependent Manner ◽  
Vascular Effect ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasorelaxant Effect ◽  
Antioxidant Agents

Caryocar brasilienseCamb. “pequi” is a native plant from the Cerrado region of Brazil that contains bioactive components reported to be antioxidant agents. Previous work has demonstrated that dietary supplementation with pequi decreased the arterial pressure of volunteer athletes. We found that the crude hydroalcoholic extract (CHE) ofC. brasilienseleaves relaxed, in a concentration-dependent manner, rat aortic rings precontracted with phenylephrine, and that the butanolic fraction (BF) produced an effect similar to that of the CHE. Aortic relaxation induced by BF was abolished by endothelium removal, by incubation of the nitric oxide synthase inhibitor L-NAME, or the soluble guanylatecyclase inhibitor ODQ. However, incubation with atropine and pyrilamine had no effect on the BF-induced vasorelaxation. Moreover, this effect was not inhibited by indomethacin and tetraethylammonium. The concentration-response curve to calcium in denuded-endothelium rings was not modified after incubation with BF, and the vasorelaxation by BF in endothelium-intact rings precontracted with KCl was abolished after incubation with L-NAME. In addition, administration of BF in anesthetized rats resulted in a reversible hypotension. The results reveal thatC. brasiliensepossesses both in vivo and in vitro activities and that the vascular effect of BF involves stimulation of the nitric oxide/cyclic GMP pathway.

Anti-Nociceptive and Anti-Inflammatory Effects of Angelicae Dahuricae Radix Through Inhibition of the Expression of Inducible Nitric Oxide Synthase and NO Production

2008 ◽  
Vol 36 (05) ◽  
pp. 913-928 ◽  
Author(s):  
Ok-Hwa Kang ◽  
Hee-Sung Chae ◽  
You-Chang Oh ◽  
Jang-Gi Choi ◽  
Young-Seob Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Formalin Test ◽  
No Production ◽  
Dependent Manner ◽  
Paw Edema ◽  
Sleeping Time ◽  
Anti Inflammatory ◽  
Angelicae Dahuricae Radix ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The extract of Angelicae Dahuricae Radix has traditionally been used as an anti-noceptive remedy in China. In this study, the methanol extract of Angelicae Dahuricae Radix (MEAD) was evaluated to determine if it has anti-noceptive and anti-inflammatory action. The anti-nociceptive activities of MEAD were evaluated by determining the writhing response and sleeping time, as well as by a formalin test. In addition, the anti-inflammatory activities of MEAD were evaluated by a vascular permeability test as well as by measuring the carrageenan-induced paw edema and conducting a myeloperoxidase (MPO) assay. MEAD (600 and 1200 mg/kg) exhibited anti-inflammatory effects on acetic acid-induced vascular permeability, carrageenan-induced paw edema, and MPO activity. Moreover, the results of the formalin test, the acetic acid-induced writhing response and the pentobarbital-induced sleeping time indicated that MEAD had anti-nociceptive effects that occurred in a concentration-dependent manner. To determine the mechanism by which MEAD exerted its effects on the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by treated murine macrophage RAW 264.7 cells was evaluated. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by MEAD in a dose-dependent manner. Furthermore, MEAD inhibited the activating phosphorylation of ERK1/2. These results provide a scientific basis that explains the mechanism by which Angelicae Dahuricae Radix relieves inflammatory pain.

scholarly journals Antiadipogenic Effects ofAster glehniExtract: In Vivo and In Vitro Effects

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Heon-Myung Lee ◽  
Gabsik Yang ◽  
Tae-Gue Ahn ◽  
Myung-Dong Kim ◽  
Agung Nugroho ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Control Diet ◽  
Epididymal Adipose Tissue ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Master Regulators ◽  
In Vitro Effects

Aster glehni(AG) is a Korean traditional herb that grows in Ulleungdo Island, Republic of Korea. None of the several reports on AG include a determination of the effect of AG on adipogenesis. The primary aim of this study was to determine whether AG attenuates adipogenesis in mouse 3T3-L1 cells and epididymal fat tissue. AG blocked the differentiation of 3T3-L1 preadipocytes in a concentration-dependent manner and suppressed the expression of adipogenesis-related genes such asPPARγ,C/EBPα, andSREBP1c, the master regulators of adipogenesis. Male C57BL/6J mice were divided randomly and equally into 4 diet groups: control diet (CON), high-fat diet (HFD), HFD with 1% AG extract added (AG1), and HFD with 5% AG extract added (AG5). The experimental animals were fed HFD and the 2 combinations for 10 weeks. Mice fed HFD with AG gained less body weight and visceral fat-pad weight than did the mice fed HFD alone. Moreover, AG inhibited the expression of important adipogenic genes such asPPARγ,C/EBPα,SREBP1c,LXR, and leptin in the epididymal adipose tissue of the mice treated with AG1 and AG5. These findings indicate antiadipogenic and antiobesity effects of AG and suggest its therapeutic potential in obesity and obesity-related diseases.

scholarly journals Monoterpenoids from the Fruits of Amomum tsao-ko Have Inhibitory Effects on Nitric Oxide Production

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 257
Author(s):  
Seong Su Hong ◽  
Ji Eun Lee ◽  
Yeon Woo Jung ◽  
Ju-Hyoung Park ◽  
Jung A. Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Diseases ◽  
Interleukin 1 ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Dependent Manner ◽  
Interleukin 1 Beta ◽  
Inhibitory Effects ◽  
Concentration Dependent Manner ◽  
First Time

In our search for novel plant-derived inhibitors of nitric oxide (NO) with potential for treating inflammatory diseases, the phytochemicals of Amomum tsao-ko fruits were investigated, leading to the isolation of one bicyclic nonane (1), three menthene skeleton monoterpenoids (2–4), and two acyclic monoterpenoids (5 and 6). Their structures were identified using one- and two-dimensional nuclear magnetic resonance spectroscopy, and mass spectrometry. To the best of our knowledge, compounds 2–5 were obtained from the genus Amomum for the first time. All isolates were tested for their ability to inhibit lipopolysaccharide-stimulated NO overproduction in RAW264.7 cells. Compound 4 was found to inhibit NO production. Western blotting analysis indicated that active compound 4 can regulate inducible NO synthase expression. In addition, lipopolysaccharide-induced interleukin 1 beta and interleukin-6 overproduction was reduced in a concentration-dependent manner.

Comparison of Antiplatelet Effects of Two Nitric Oxide-donating Agents, FR146801 and FK409

1998 ◽  
Vol 79 (03) ◽  
pp. 620-624 ◽  
Author(s):  
Yasuko Kato ◽  
Shinichi Fukuyama ◽  
Mitsuko Ohno ◽  
Shigetaka Nishino ◽  
Masayuki Kato ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Thrombus Formation ◽  
Hypotensive Effect ◽  
Cgmp Level ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Antiplatelet Effect

SummaryIn the present study, we examined the antiplatelet effects of the two nitric oxide (NO)-donating agents, (±)-N -[(E)-4-ethyl-3-[(Z)hydroxyimino]-6-methyl-5-nitro-3-heptenyl]-3-pyridinecarboxamide (FR146801), a more stable analog of FK409 ((±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide), and FK409 in in vitro and in vivo experiments. FR146801 and FK409 inhibited ADP- and collagen-induced platelet aggregation in human and rat platelet-rich plasma in a concentration-dependent manner, however, the inhibitory effect of FR146801 was weaker than that of FK409. In human washed platelets (WP), FR146801 and FK409 inhibited collagen-induced platelet aggregation in a concentration-dependent manner. The inhibitory effects of FR146801 and FK409 on platelet aggregation were closely reflected by the increase in the intraplatelet cGMP level. This intensely suggests that the antiplatelet activities of FR146801 and FK409 are due to NO-released from them. In the rat extracorporeal shunt model, FR146801 inhibited thrombus formation dose-dependently and its inhibition was significant at 10 mg/kg, p.o. FK409 suppressed thrombus formation significantly at 1.0 mg/kg, p.o., at which it induced significant hypotension, whereas FR146801 did not show any significant hypotensive effect even at 10 mg/kg, p.o. These results suggest that FR146801 has desirable antiplatelet effects both in vitro and in vivo and that its in vivo antiplatelet effect is more selective than its hypotensive effect, while FK409 does not show a selective antiplatelet effect in vivo.

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