title: Naringin lauroyl ester inhibits lipopolysaccharide-induced activation of nuclear factor κB signaling in macrophages.
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.
authors.affiliation: a Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Sakai , Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hattori
authors.affiliation: b Department of Biological Science, Graduate School of Science , Osaka Prefecture University , Sakai , Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Tsutsuki
authors.affiliation: a Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Sakai , Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Nakazawa
authors.affiliation: a Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Sakai , Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ueda
authors.affiliation: b Department of Biological Science, Graduate School of Science , Osaka Prefecture University , Sakai , Japan.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Ihara
authors.affiliation: a Division of Applied Life Sciences, Graduate School of Life and Environmental Sciences , Osaka Prefecture University , Sakai , Japan.
authors.forename: Tatsuji
authors.initials: T
authors.lastname: Sakamoto
mesh_terms: D000215:Acylation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004800:Enzymes, Immobilized / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D005227:Fatty Acids / Q000737:chemistry; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry; D005786:Gene Expression Regulation; D008049:Lipase / Q000737:chemistry; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D020103:Rhizomucor / Q000737:chemistry; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004800:Enzymes, Immobilized; D004952:Esters; D005227:Fatty Acids; D044950:Flavanones; D005656:Fungal Proteins; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D008049:Lipase; C005274:naringin
keywords: Naringin; acylation; anti-inflammatory activity; nuclear factor κB