Effects of esculetin on lipopolysaccharide (LPS)-induced acute lung injury via regulation of RhoA/Rho Kinase/NF-кB pathways in vivo and in vitro

Free Radic Res. 2015;49(12):1459-68. doi: 10.3109/10715762.2015.1087643.

Abstract

The purpose of the present study was to investigate the protective effect of esculetin (ES) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the lung epithelial A549 cells. Mice were intragastrically administered with ES (20 and 40 mg/kg) 1 h prior to LPS challenge. ES pretreatment at doses of 20 and 40 mg/kg effectively attenuated LPS-induced lung histopathological change, myeloperoxidase or MPO activity, inflammatory cells infiltration, pulmonary wet-to-dry weight ratio, and the generation of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vivo and in vitro. Furthermore, we demonstrated that ES blocked the activation of NF-кB and RhoA/Rho kinase pathways in LPS-induced mice and A549 cells. The results suggested that ES exhibited protective effect on ALI and might attribute partly to the inhibition of NF-кB and RhoA/Rho kinase pathways in vivo and in vitro.

Keywords: Esculetin; RhoA/Rho kinase/NF-кB; acute lung injury; lipopolysaccharide (LPS); lung epithelial A549.

MeSH terms

  • Acute Lung Injury / metabolism*
  • Animals
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Cell Line
  • Disease Models, Animal
  • Enzyme Activation / drug effects*
  • Female
  • Humans
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Signal Transduction / drug effects*
  • Umbelliferones / pharmacology*
  • rho GTP-Binding Proteins / metabolism
  • rho-Associated Kinases / metabolism
  • rhoA GTP-Binding Protein

Substances

  • Antioxidants
  • Lipopolysaccharides
  • NF-kappa B
  • Umbelliferones
  • rho-Associated Kinases
  • RhoA protein, mouse
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • esculetin