title: Dimethyl cardamonin inhibits lipopolysaccharide-induced inflammatory factors through blocking NF-kappaB p65 activation.
abstract: This study has found that dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC), a naturally occurring chalcone, showed potent anti-inflammatory effects in vitro and in vivo. In a cellular model of inflammation, DMC inhibited production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and attenuated expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1 beta, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). DMC prevented nuclear translocation of the nuclear factor-kappaB (NF-kappaB) p65 subunit by reducing inhibitor of kappaB alpha (I-kappaB alpha) phosphorylation and degradation, which resulted in a suppression of NF-kappaB activities for its target genes. In a mouse model of endotoxin shock, the intraperitoneal injection (i.p.) of DMC (1-50mg/kg) suppressed TNF-alpha, IL-6 and IL-1 beta secretion in LPS-induced mouse blood serum. These results suggest that DMC exerts anti-inflammatory effects through blocking NF-kappaB activation, therefore, DMC may act as an effective therapeutic strategy against a variety of inflammatory diseases.
authors.affiliation: Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Hyeonseok
authors.initials: H
authors.lastname: Ko
authors.forename: Jin-Soo
authors.initials: JS
authors.lastname: Park
authors.forename: Im-Ho
authors.initials: IH
authors.lastname: Han
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; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047188:Chalcones / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000032:analysis; D015232:Dinoprostone / Q000032:analysis; D007249:Inflammation / Q000188:drug therapy; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D010766:Phosphorylation; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C501649:2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone