Angelicin regulates LPS-induced inflammation via inhibiting MAPK/NF-κB pathways

J Surg Res. 2013 Nov;185(1):300-9. doi: 10.1016/j.jss.2013.05.083. Epub 2013 Jun 19.

Abstract

Background: Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit. The purpose of this study was to investigate the protective ability of angelicin against inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced in vivo acute lung injury model.

Materials and methods: The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 in the culture supernatants of RAW 264.7 cells were determined 24 h after LPS administration. ALI was induced by intratracheal instillation of LPS. Six hours after LPS inhalation, bronchoalveolar lavage fluid and lung tissue samples were obtained for enzyme-linked immunosorbent assay, histologic, and Western blotting analyses.

Results: The results showed that pretreatment with angelicin markedly downregulated TNF-α and IL-6 levels in vitro and in vivo, and significantly decreased the amount of inflammatory cells, lung wet-to-dry weight ratio, and myeloperoxidase activity in LPS-induced ALI mice. Furthermore, Western blotting analysis results demonstrated that angelicin blocked the phosphorylation of IκBα, NF-κBp65, p38 MAPK, and JNK in LPS-induced ALI.

Conclusions: These results suggest that angelicin was potentially advantageous to prevent inflammatory diseases by inhibiting NF-κB and MAPK pathways. Our data indicated that angelicin might be a potential new agent for prevention of inflammatory reactions and diseases in the clinic.

Keywords: Angelicin; Cytokines; Lipopolysaccharide; MAPK; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / immunology
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Disease Models, Animal
  • Furocoumarins / chemistry
  • Furocoumarins / pharmacology*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / immunology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / immunology*
  • NF-kappa B / metabolism
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy*
  • Pneumonia / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Furocoumarins
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • angelicin