title: Anti-inflammatory effect of sinomenine by inhibition of pro-inflammatory mediators in PMA plus A23187-stimulated HMC-1 Cells.
abstract: OBJECTIVE
  Sinomenine is an alkaloid compound and a prominent anti-inflammatory agent found in the root of the climbing plant Sinomenium acutum. However, its effects on the mechanism of human mast cell line (HMC)-1-mediated inflammation remained unknown.
  
  
  METHODS
  To provide insight into the biological effects of sinomenine, we examined its influence on the pro-inflammatory cytokine production in HMC-1 cells stimulated by phorbol 12-myristate-13-acetate (PMA) plus A23187 by evaluating the stimulated cells in the presence or absence of sinomenine. In the present study, the pro-inflammatory cytokine production was measured using ELISA, Reverse Transcription-polymerase chain reaction (RT-PCR) and nuclear factor (NF)-kappaB, mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Also, cyclooxygenase (COX)-2 expression was measured through Western blot and RT-PCR analysis.
  
  
  RESULTS
  Sinomenine inhibited the pro-inflammatory cytokine production induced by PMA plus A23187 in a dose-dependent manner. Furthermore, sinomenine inhibited the phosphorylations of extracellular signal-regulated kinase (ERK) and p38 MAPKs as well as the translocation of NF-kappaB p65 through reduced IkappaBalpha degradation. In addition, sinomenine suppressed COX-2 protein and mRNA expression dose-dependently.
  
  
  CONCLUSIONS
  Taken together, the results of this study indicate that the anti-inflammatory effects of sinomenine may occur via the inhibition of pro-inflammatory cytokine and COX-2 production through the inhibition of MAPKs and NF-kappaB pathway activation by PMA plus A23187 stimulation in HMC-1 cells.
authors.affiliation: College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk, Korea
authors.forename: Y C
authors.initials: YC
authors.lastname: Oh
authors.forename: O H
authors.initials: OH
authors.lastname: Kang
authors.forename: S B
authors.initials: SB
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Mun
authors.forename: C B
authors.initials: CB
authors.lastname: Park
authors.forename: Y G
authors.initials: YG
authors.lastname: Kim
authors.forename: Y I
authors.initials: YI
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Han
authors.forename: J H
authors.initials: JH
authors.lastname: Keum
authors.forename: D W
authors.initials: DW
authors.lastname: Shin
authors.forename: J Y
authors.initials: JY
authors.lastname: Ma
authors.forename: D Y
authors.initials: DY
authors.lastname: Kwon
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009019:Morphinans / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D009019:Morphinans; D016328:NF-kappa B; D000001:Calcimycin; C009271:sinomenine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013755:Tetradecanoylphorbol Acetate