title: Use of scopoletin to inhibit the production of inflammatory cytokines through inhibition of the IkappaB/NF-kappaB signal cascade in the human mast cell line HMC-1.
abstract: Scopoletin (6-methoxy-7-hydroxycoumarin) is a coumarin compound and a pharmacologically active agent that has been isolated from several plant species. However, as yet there is no clear explanation of how scopoletin affects the production of inflammatory cytokine. We therefore used cells from the human mast cell line (HMC-1) to investigate this effect. Scopoletin significantly and dose-dependently inhibits the way in which phorbol 12-myristate 13-acetate (PMA) plus A23187 induces the production of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 (P<0.05). The maximal rates at which scopoletin (0.2 mM) inhibited the production of TNF-alpha, IL-6, and IL-8 were 41.6%+/-4.2%, 71.9%+/-2.5%, and 43.0%+/-5.7%, respectively. In activated HMC-1 cells, the expression level of nuclear factor (NF)-kappaB/Rel A protein was increased in the nucleus whereas the level of NF-kappaB/Rel A in nucleus was decreased by treatment with scopoletin. Scopoletin decreased PMA plus A23187-induced luciferase activity. Scopoletin also inhibits IkappaBalpha phosphorylation and degradation in cytoplasm. These results indicate that scopoletin has a potential regulatory effect on inflammatory reactions that are mediated by mast cells.
authors.affiliation: College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea.
authors.forename: Phil-Dong
authors.initials: PD
authors.lastname: Moon
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: An
authors.forename: Seok-Jae
authors.initials: SJ
authors.lastname: Park
authors.forename: Hyung-Ryong
authors.initials: HR
authors.lastname: Kim
authors.forename: Seong-Gyu
authors.initials: SG
authors.lastname: Ko
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Um
authors.forename: Seung-Heon
authors.initials: SH
authors.lastname: Hong
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D012603:Scopoletin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D000001:Calcimycin; D006632:Histamine; D012603:Scopoletin; D013755:Tetradecanoylphorbol Acetate