title: Inhibitory effects of aurentiacin from Syzygium samarangense on lipopolysaccharide-induced inflammatory response in mouse macrophages.
abstract: Aurentiacin is a chalcone isolated from Syzygium samarangense. In the present study, we examined the anti-inflammatory effects of aurentiacin in lipopolysaccharide (LPS)-stimulated mouse macrophages. Aurentiacin significantly inhibited LPS-induced nitric oxide (NO) production in RAW264.7 cells concomitantly with the suppression of inducible nitric oxide synthase (iNOS) expression. Aurentiacin also reduced the mRNA levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Electrophoretic mobility shift assays (EMSAs) and reporter gene assays indicated that DNA binding and transcriptional activities of nuclear factor-κB (NF-κB)/p65 were decreased by aurentiacin in LPS-stimulated RAW264.7 cells. Moreover, results from chromatin immunoprecipitation (ChIP) assays over the promoter region of the iNOS gene were in agreement with the EMSA results. Pretreatment with aurentiacin prevented the nuclear translocation of p65 by blocking the phosphorylation of I-κB kinase (IKK). Aurentiacin also attenuated the phosphorylation (Ser536) and acetylation (Lys310) of p65 and phosphorylation of MAPKs. In an inflammatory animal model, the intraperitoneal (i.p.) injection of aurentiacin suppressed the release of pro-inflammatory cytokines. Moreover, the level of iNOS protein ex vivo was decreased by aurentiacin similar to the result in vitro. Taken together, these results suggest that aurentiacin shows anti-inflammatory activity related to the inhibition of NF-κB activation.
authors.affiliation: Natural Medicine Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do 210-340, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Han-Cheon
authors.initials: HC
authors.lastname: Kim
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
authors.forename: Evangeline C
authors.initials: EC
authors.lastname: Amor
authors.forename: Jong Wha
authors.initials: JW
authors.lastname: Lee
authors.forename: Hyun Ok
authors.initials: HO
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D047188:Chalcones / Q000494:pharmacology / Q000627:therapeutic use*; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D051550:I-kappa B Kinase / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015848:Interleukin-5 / Q000235:genetics; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D027842:Syzygium / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: C573494:2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone; D047188:Chalcones; D015848:Interleukin-5; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051550:I-kappa B Kinase