Abstract
Naringin (Nar) has antioxidant and anti-inflammatory properties. It was recently reported that enzymatic modification of Nar enhanced its functions. Here, we acylated Nar with fatty acids of different sizes (C2-C18) using immobilized lipase from Rhizomucor miehei and investigated the anti-inflammatory effects of these molecules. Treatment of murine macrophage RAW264.7 cells with Nar alkyl esters inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production, with Nar lauroyl ester (Nar-C12) showing the strongest effect. Furthermore, Nar-C12 suppressed the LPS-induced expression of inducible NO synthase by blocking the phosphorylation of inhibitor of nuclear factor (NF)-κB-α as well as the nuclear translocation of NF-κB subunit p65 in macrophage cells. Analysis of Nar-C12 uptake in macrophage cells revealed that Nar-C12 ester bond was partially degraded in the cell membrane and free Nar was translocated to the cytosol. These results indicate that Nar released from Nar-C12 exerts anti-inflammatory effects by suppressing NF-κB signaling pathway.
Keywords:
Naringin; acylation; anti-inflammatory activity; nuclear factor κB.
MeSH terms
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Acylation
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Line
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Cell Nucleus / drug effects
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Cell Nucleus / metabolism
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Cytosol / drug effects
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Cytosol / metabolism
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Enzymes, Immobilized / chemistry
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Esters / chemistry
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Fatty Acids / chemistry
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Flavanones / chemistry
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Flavanones / pharmacology*
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Fungal Proteins / chemistry
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Gene Expression Regulation
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Lipase / chemistry
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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 / cytology
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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Nitric Oxide / antagonists & inhibitors*
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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Phosphorylation / drug effects
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Protein Transport / drug effects
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Rhizomucor / chemistry
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Signal Transduction
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Transcription Factor RelA / antagonists & inhibitors*
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Transcription Factor RelA / genetics
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Transcription Factor RelA / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Enzymes, Immobilized
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Esters
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Fatty Acids
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Flavanones
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Fungal Proteins
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Lipopolysaccharides
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Rela protein, mouse
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Transcription Factor RelA
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Lipase
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naringin