Abstract
Diospyros lotus is traditionally used for the treatment of diabetes, diarrhea, tumor, and hypertension. The purpose of this study was to investigate the anti-inflammatory effect and underlying molecular mechanisms of myricetin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Myricetin dose-dependently suppressed the production of pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in LPS-stimulated RAW264.7 macrophages. Myricetin administration decreased the production of NO, iNOS, TNF-α, IL-6, and IL-12 in mice. Myricetin decreased NF-κB activation by suppressing the degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Moreover, myricetin attenuated the phosphorylation of STAT1 and the production of IFN-β in LPS-stimulated RAW264.7 macrophages. Furthermore, myricetin induced the expression of HO-1 through Nrf2 translocation. In conclusion, these results suggest that myricetin inhibits the production of pro-inflammatory mediators through the suppression of NF-κB and STAT1 activation and induction of Nrf2-mediated HO-1 expression in LPS-stimulated RAW264.7 macrophages.
Keywords:
HO-1; NF-κB; STAT1; anti-inflammation; myricetin.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Line
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Diospyros / chemistry*
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Flavonoids / isolation & purification
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Flavonoids / pharmacology*
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Gene Expression Regulation
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Heme Oxygenase-1 / genetics
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Heme Oxygenase-1 / immunology
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Inflammation / prevention & control
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Interferon-beta / genetics
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Interferon-beta / immunology
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Lipopolysaccharides / antagonists & inhibitors
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Lipopolysaccharides / pharmacology*
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Macrophage Activation / drug effects
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Macrophages / drug effects
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Macrophages / immunology
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Macrophages / pathology
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Male
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Membrane Proteins / genetics
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Membrane Proteins / immunology
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Mice
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Mice, Inbred BALB C
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NF-E2-Related Factor 2 / genetics
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NF-E2-Related Factor 2 / immunology
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NF-KappaB Inhibitor alpha / genetics
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NF-KappaB Inhibitor alpha / immunology
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NF-kappa B / genetics*
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NF-kappa B / immunology
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / immunology
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Phosphorylation
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STAT1 Transcription Factor / genetics*
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STAT1 Transcription Factor / immunology
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Flavonoids
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Lipopolysaccharides
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Membrane Proteins
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NF-E2-Related Factor 2
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NF-kappa B
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Nfe2l2 protein, mouse
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STAT1 Transcription Factor
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Stat1 protein, mouse
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Tumor Necrosis Factor-alpha
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NF-KappaB Inhibitor alpha
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Nitric Oxide
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myricetin
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Interferon-beta
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Heme Oxygenase-1
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Hmox1 protein, mouse