title: (E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one, a novel licochalcone B derivative compound, suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice.
abstract: Activated macrophages mediate inflammation, as they release nitric oxide and pro-inflammatory cytokines in various inflammatory diseases. Suppressing macrophage activation may alleviate inflammatory processes. Here, we report that (E)-3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one (DDP), a novel licochalcone B derivative compound, inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. In vitro experiments showed that DDP suppressed the generation of nitric oxide and pro-inflammatory cytokines by suppressing the activation of nuclear factor-κB and activator protein-1 and simultaneously inhibited its upstream inflammatory signaling cascades in lipopolysaccharide in RAW264.7 cells. In an animal model, DDP protected BALB/c mice from lipopolysaccharide-induced endotoxin shock, possibly through inhibition of the production of inflammatory cytokines. DDP inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.
authors.affiliation: Department of Biomedical Science, Catholic University of Daegu, Gyeongsan-Si, Republic of Korea.
authors.forename: Ju-Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Chemistry and Institute of Natural Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Jong-Gab
authors.initials: JG
authors.lastname: Jun
authors.affiliation: Department of Biomedical Science, Catholic University of Daegu, Gyeongsan-Si, Republic of Korea. Electronic address: toto0818@cu.ac.kr.
authors.forename: Jin-Kyung
authors.initials: JK
authors.lastname: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000032:analysis / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism; D013237:Stereoisomerism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors; D015850:Interleukin-6
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047188:Chalcones; D053583:Interleukin-1beta; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides; D048308:Mitogen-Activated Protein Kinase 14; D016328:NF-kappa B; D009569:Nitric Oxide; D009573:Nitrites; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C000614159:3-(3,4-dihydroxy-2-methoxyphenyl)-1-(2,4-dihydroxyphenyl)prop-2-en-1-one; C577686:interleukin-6, mouse; D015850:Interleukin-6; C440499:lipopolysaccharide, Escherichia coli O111 B4; C541528:licochalcone B
keywords: Cytokines; Endotoxin shock; Inflammation; LPS; Macrophages