Preventive effect of bis-eugenol, a eugenol ortho dimer, on lipopolysaccharide-stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages

Murakami, Yukio; Shoji, Masao; Hanazawa, Shigemasa; Tanaka, Shoji; Fujisawa, Seiichiro

doi:10.1016/s0006-2952(03)00419-2

Cited by 62 publications

(43 citation statements)

References 22 publications

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“…Expression of COX-2 is stimulated by NO through the cAMP-response element (14), and thus, the cytotoxicity of NO has been considered to be closely related to the action of increased prostaglandins resulting from the induction of COX-2 (10). Several lines of evidence showed that anti-inflammatory action of eugenol compounds depends on the inhibition of the COX-2 expression (6,13,17). As demonstrated in the present study, eugenol and isoeugenol decreased the production of NO by inhibiting the expression of iNOS protein, and further decreased the expression of COX-2 protein, implying that eugenol compounds can act as principal anti-inflammatory mediators.…”

Section: Discussionsupporting

confidence: 81%

“…antioxidant (15,16) and anti-inflammatory actions (6,13,17). Our recent studies showed that eugenol compounds exhibit antioxidant properties by inhibiting iron-mediated lipid peroxidation and copper-dependent LDL oxidation (5), which are regarded as an important risk factor of atherosclerotic vascular diseases (1,22).…”

Section: Fig 2 Effect Of Eugenol (A) and Isoeugenol (B)mentioning

confidence: 99%

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Inhibitory action of eugenol compounds on the production of nitric oxide in RAW264.7 macrophages

Tsubouchi

Qiao

et al. 2006

Biomed. Res.

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Effects of eugenol compounds on the production of nitric oxide (NO) in RAW264.7 macrophages were analyzed in relation to the anti-inflammatory action of these compounds. Eugenol and isoeugenol inhibited lipopolysaccharide (LPS)-dependent production of NO, which was due to the inhibition of protein synthesis of inducible nitric oxide synthase (iNOS). Isoeugenol showed the most effective inhibitory effect and eugenol was less effective. LPS-dependent expression of cyclooxygenase-2 (COX-2) protein was also inhibited markedly by isoeugenol, and less effectively by eugenol. Anti-inflammatory action of eugenol compounds may be explained by the inhibition of NO production and COX-2 expression, the pro-inflammatory mediators.Eugenol with a methoxyphenol structure is a principal constituent of bay leaves, allspice, and the oil of cloves that originate from the Syzygium species (7). Eugenol is widely used as a flavoring agent in cosmetic and food products (9), and is also utilized as an antiseptic drug in dentistry (2, 21). Isoeugenol, an isomer of eugenol is found in monkey orange (19), and shows anti-oxidant properties (15, 16). Recently we analyzed inhibitory effects of eugenol compounds on metal-mediated oxidation of membrane lipids and LDL (low density lipoprotein) that are an important risk factor for the development of atherosclerotic vascular disease (1, 22), and the metal-reducing activity of eugenol and isoeugenol may participate in the antioxidant action of these compounds (5). Development of oxidative damage is closely related to the reactive nitrogen species in addition to active oxygen: that is, peroxynitrite produced by the reaction of superoxide radical with nitric oxide shows potent cytotoxic effects. For further analyses of anti-oxidant, anti-inflammatory and anti-septic properties of eugenol compounds, we analyzed the effect of eugenol compounds on the production of NO and the expression of the iNOS protein. Eugenol compounds, in particular isoeugenol showed a potent inhibitory effect of LPS-mediated expression of iNOS protein, and COX2 protein in RAW264.7 macrophages. Anti-inflammatory action of eugenol compounds can be explained at least, in part by the inhibition of iNOS induction. MATERIALS AND METHODSReagents. The sources of materials used in this work were as follows: eugenol, isoeugenol, lipopolysaccharide (LPS), 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolidum bromide (MTT) from Sigma-Aldrich-Japan (Tokyo, Japan), rabbit anti-Cu/ Zn SOD and anti-nitric oxide synthase II (iNOS) antibodies from Stressgen Biotechnologies Corp (Victoria, BC, Canada), mouse anti-phospho-Iκ-Bα (Ser32/36) (5A5) antibody and mouse anti-COX2 antibody from Cell Signaling Technology (Heidel-

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Section: Discussionsupporting

confidence: 81%

Section: Fig 2 Effect Of Eugenol (A) and Isoeugenol (B)mentioning

confidence: 99%

Inhibitory action of eugenol compounds on the production of nitric oxide in RAW264.7 macrophages

Tsubouchi

Qiao

et al. 2006

Biomed. Res.

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“…However, limited scientific evidence regarding the effectiveness of these natural derivatives, and lack of mechanistic understanding has prevented their incorporation into mainstream medicine and their application in human therapy. Eugenol, an important bioactive compound, isolated from O. gratissimum, has a number of beneficial roles [17][18][19][20][21][22][23][41][42][43]. We initially observed its cytotoxic profile in murine peritoneal macrophages by MTT assay, and determined its least comparative cytotoxic concentration to be 15 μg/ml, whereas concentrations higher than 15 μg/ml showed significantly increased cytotoxicity (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Eugenol isolated from the cortex of Eugenol caryophyllata (clove) inhibited the activity and gene expression of inducible cyclooxygenase (COX-2) in lipopolysacharide (LPS) activated mouse macrophage cells [19]. Eugenol compounds show various biological effects including antioxidants [20,21], and antiinflammatory action [19,22]. It was also established that, eugenol could play a principal role in the anti-inflammatory mediators by decreasing LPS mediate NO production through inhibition of iNOS expression [23].…”

Section: Introductionmentioning

confidence: 99%

Alteration of immune functions and Th1/Th2 cytokine balance in nicotine-induced murine macrophages: Immunomodulatory role of eugenol and N-acetylcysteine

Mahapatra

Bhattacharjee

Chakraborty

et al. 2011

International Immunopharmacology

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“…For example, naturally occurring compounds isolated from sesaminol and eugenol were found to be anti-inflammatory through the inhibition of NF-κB activity in macrophages (Murakami et al, 2003(Murakami et al, , 2005Lee et al, 2006a). It is well known that macrophages play a crucial role in both non-specific and acquired immune responses, and that macrophage activation by LPS leads to a functionally diverse series of responses including the production of pro-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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Citral is a major compound of lemongrass (Cymbopogon citratus L.) that has many pharmacological activities such as anti-fungal and anti-bacterial effects. In this study, we investigated the anti-inflammatory effect of citral and defined its mechanism of action in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Citral (3-12 microg/mL) significantly inhibited LPS-induced nitric oxide (NO) production in a concentration-dependent manner (IC50: 6.5 microg/mL). Furthermore, it was found that citral effectively inhibited the transcriptional activity and expression of iNOS, and potently suppressed the DNA binding activity and nuclear translocation of NF-kappa B as well as I kappa B phosphorylation in a concentration dependent manner. These results suggest that citral is anti-inflammatory, and its effects may be due to the inhibition of NO production through the suppression of NF-kappa B activation.

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Preventive effect of bis-eugenol, a eugenol ortho dimer, on lipopolysaccharide-stimulated nuclear factor kappa B activation and inflammatory cytokine expression in macrophages

Cited by 62 publications

References 22 publications

Inhibitory action of eugenol compounds on the production of nitric oxide in RAW264.7 macrophages

Inhibitory action of eugenol compounds on the production of nitric oxide in RAW264.7 macrophages

Alteration of immune functions and Th1/Th2 cytokine balance in nicotine-induced murine macrophages: Immunomodulatory role of eugenol and N-acetylcysteine

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

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