title: Inhibitory effects of 4-hydroxyderricin and xanthoangelol on lipopolysaccharide-induced inflammatory responses in RAW264 macrophages.
abstract: The Japanese herb, Ashitaba (Angelica keiskei Koidzumi), contains two prenylated chalcones, 4-hydroxyderricin and xanthoangelol, which are considered to be the major active compounds of Ashitaba. However, their effects on inflammatory responses are poorly understood. In the present study, we investigated the effects and underlying molecular mechanisms of 4-hydroxyderricin and xanthoangelol on lipopolysaccharide (LPS)-induced inflammatory responses in RAW264 mouse macrophages. LPS-mediated production of nitric oxide (NO) was markedly reduced by 4-hydroxyderricin (10 μM) and xanthoangelol (5 μM) compared with their parent compound, chalcone (25 μM). They also inhibited LPS-induced secretion of tumor necrosis factor-alpha (TNF-α) and expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). Although chalcone decreased the DNA-binding activity of both activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB), 4-hydroxyderricin and xanthoangelol suppressed only AP-1 and had no effect on NF-κB. On the other hand, all of the tested chalcones reduced the phosphorylation (at serine 536) level of the p65 subunit of NF-κB. 4-Hydroxyderricin and xanthoangelol may be promising for the prevention of inflammatory diseases.
authors.affiliation: Organization of Advanced Science and Technology, Kobe University , 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Yasuda
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Miki
authors.initials: M
authors.lastname: Miyashita
authors.forename: Mayu
authors.initials: M
authors.lastname: Okumura
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
authors.forename: Hajime
authors.initials: H
authors.lastname: Ohigashi
mesh_terms: D029969:Angelica / Q000737:chemistry; D000818:Animals; D002460:Cell Line; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C068243:4-hydroxyderricin; D002599:Chalcone; C068244:xanthoangelol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2
keywords: 4-hydroxyderrin; AP-1; Angelica keiskei Koidzumi (Ashitaba); NF-κB; anti-inflammation; xanthoangelol