Inhibitory effect of citral on NO production by suppression of iNOS expression and NF-κB activation in RAW264.7 cells

Lee, Hwa Jeong; Jeong, Heon Sang; Kim, Dae Joong; Noh, Young Hee; Yuk, Dong Yeon; Hong, Jin Tae

doi:10.1007/s12272-001-1162-0

Cited by 88 publications

(65 citation statements)

References 32 publications

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“…Some studies have been conducted with citral, the main volatile compound of the essential oil of Cymbopogon citratus (Cy) (Cheel et al, 2005;Lee et al, 2008), however little is known about the properties and mechanisms of action of the fixed compounds, namely polyphenols. Therefore, in the present study we analyzed their anti-inflammatory potential and evaluated some molecular targets of these extracts in LPS-stimulated Raw 264.7 cells.…”

Section: Evaluation Of the Anti-inflammatory Properties And Molecularmentioning

confidence: 99%

Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages

Francisco

Figueirinha

Neves

et al. 2011

Journal of Ethnopharmacology

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Please cite this article as: Francisco, V., Figueirinha, A., Neves, B.M., García-Rodríguez, C., Lopes, M.C., Cruz, M.T., Batista, M.T., Cymbopogon citratus as source of new and safe anti-inflammatory drugs: bio-guided assay using lipopolysaccharide-stimulated macrophages, Journal of Ethnopharmacology (2010Ethnopharmacology ( ), doi:10.1016Ethnopharmacology ( /j.jep.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 30A c c e p t e d M a n u s c r i p t 1 Graphical abstractIn this report it was demonstrated that a lipid-and essential oil-free infusion of Cymbopogon citratus leaves (Cy), as well its polyphenols, have anti-inflammatory properties through inhibition of proinflammatory signaling pathways and nitric oxide production in lipopolysaccharide-stimulated macrophages. These evidences support the use of Cymbopogon citratus in traditional medicine and indicate that it could be a natural source of new and safe anti-inflammatory drugs. TitleCymbopogon citratus as source of new and safe anti-inflammatory drugs: bio-guided assay using lipopolysaccharide-stimulated macrophages Aim of the study: The aim of this study is to explore the anti-inflammatory properties of Cymbopogon citratus leaves and their polyphenol-rich fractions (PFs), as well its mechanism of action in murine macrophages. Materials and Methods:A lipid-and essential oil-free infusion of Cy leaves was prepared (Cy extract) and fractionated by column chromatography. Anti-inflammatory properties of Cy extract (1.115 mg/ml) and its PFs, namely phenolic acids (530 µg/ml), flavonoids (97.5 µg/ml) and tannins (78 µg/ml), were investigated using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages as in vitro model. As inflammatory parameters, nitric oxide (NO) production was evaluated by Griess reaction, as well as effects on cyclooxygenase (COX-2), inducible NO synthase (iNOS) expression and on intracellular signaling pathways activation, which were analyzed by Western blot using specific antibodies. Page 3 of 30A c c e p t e d M a n u s c r i p t Conclusions: Our data provide evidence that support the usage of Cymbopogon citratus leaves extract in traditional medicine, and suggest that Cy, in particular its polyphenolic compounds, could constitute a natural source of a new and safe anti-inflammatory drugs.

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Section: Evaluation Of the Anti-inflammatory Properties And Molecularmentioning

confidence: 99%

Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages

Francisco

Figueirinha

Neves

et al. 2011

Journal of Ethnopharmacology

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“…Our data suggest that citral may also suppress COX-2 promoter activity in a PPARγ-independent manner, since activation of PPARγ was similar with citral and carvacrol. Citral has been reported to suppress the expression of inducible nitric synthase (iNOS) gene by LPS, and suppress the DNA-binding activity of the NF-kB site of the iNOS gene (Lee et al, 2008). Moreover, it has been shown to activate several TRP thermosensitive channels with different affinities: that is TRPM8 (EC 50 = 33.5 μM) and TRPA1 (EC 50 = 200 μM) (Stotz et al, 2008) (Table 1) Inoue, H., Jiang, X., Katayama, T., Osada, S., Umesono, K. and Namura, S. (2003).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of Food-derived Functional Ingredients According to Activation of PPAR and Suppression of COX-2 Expression

Nakata

Takizawa

Takai

et al. 2013

FSTR

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The peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors belonging to the nuclear receptor family. They are considered molecular targets for the prevention of lifestyle-related diseases and are involved in the control of cyclooxygenase (COX)-2 expression. COX-2, the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis, and its expression is partly controlled by PPAR. We have identified several natural chemicals, such as resveratrol, that activate PPARs and suppress COX-2 expression. In this review, we provide an evaluation of food-derived functional ingredients that target PPARs and COX-2.Keywords: PPAR, COX-2, resveratrol, essential oil, anti-lifestyle-related disease *To whom correspondence should be addressed. E-mail: inoue@cc.nara-wu.ac.jp IntroductionThe prevention of lifestyle-related diseases, such as cardiovascular disease, diabetes, and stroke, is of worldwide interest. Individuals tend to focus not only on drug therapy for prevention of these diseases, but also on the functionality of natural chemicals found in food and beverages, such as polyphenols and their polymers. A growing body of evidence supports the theory that polyphenolic compounds have activities that maintain health. Epidemiological studies have demonstrated that dietary polyphenol intake, e.g., red wine consumption, may improve endothelial function and reduce risk for cardiovascular diseases (Stoclet et al., 2004; Cordova et al., 2005;Opie et al., 2007). Although there have been numerous studies investigating food-derived functional components, the molecular mechanisms for their actions remain to be determined. We found that several natural food-derived components, such as resveratrol, activate peroxisome proliferator-activated receptors (PPARs) and suppress expression of cyclooxygenase (COX)-2. These two properties targeted specifically to PPARs and COX-2 will be important for evaluating food-derived functional components. This review discusses the effects of food-derived functional components on PPARs and COX-2, and evaluates novel functions of these compounds in relation to prevention of lifestyle-related diseases. Linkage Between PPAR and COX-2PPARs are members of a nuclear receptor family of ligand-dependent transcription factors (Mangelsdolf et al., 1995). The PPAR subfamily comprises three isotypes, PPARα, β/δ and γ, which play various roles in lipid and carbohydrate metabolism, cell proliferation and differentiation, and inflammation; they are considered molecular targets in the prevention of lifestyle-related diseases (Michalik et al., 2006;Sonoda et al., 2008). For example, PPARα agonists, such as fibrates and thiazolidine derivatives, are used to treat dyslipidemia and diabetes, respectively. Moreover, eicosapentaenoic acid, a natural ligand for PPARα, has been used as a hypolipidemic drug and has been reported to lower plasma and liver cholesterol levels in a PPARα-dependent manner (Sugiyama et al., 2008).PPARs are also invo...

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“…In this regards, Katsukawa et al (2010) identified CIT as a suppressor of COX-2 and an activator of peroxisome proliferator-activated receptors (PPAR) α and γ. Moreover, Lee et al (2008) showed that CIT inhibits NO generation through suppression of iNOS expression via inhibition of NF-κB activation.…”

Section: Resultsmentioning

confidence: 99%

Citral reduces nociceptive and inflammatory response in rodents

Quintans‐Júnior¹,

Guimarães²,

Santana³

et al. 2011

Rev. bras. farmacogn.

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Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and antiinflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001) against acetic acid (0.8%) induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05) only at higher dose (200 mg/kg) of CIT in the first phase of the test. CIT significantly reduce (p<0.001) nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg) significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg) significantly reduced (p<0.001) the leukocyte migration in the carrageenaninduced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

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Inhibitory effect of citral on NO production by suppression of iNOS expression and NF-κB activation in RAW264.7 cells

Cited by 88 publications

References 32 publications

Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages

Cymbopogon citratus as source of new and safe anti-inflammatory drugs: Bio-guided assay using lipopolysaccharide-stimulated macrophages

Evaluation of Food-derived Functional Ingredients According to Activation of PPAR and Suppression of COX-2 Expression

Citral reduces nociceptive and inflammatory response in rodents

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