Protective effect of sophocarpine on lipopolysaccharide-induced acute lung injury in mice

Int Immunopharmacol. 2019 May:70:180-186. doi: 10.1016/j.intimp.2019.02.020. Epub 2019 Feb 23.

Abstract

Sophocarpine (SOP) is a tetracyclic quinolizidine alkaloid isolated from Sophora alopecuroides L. A number of studies have shown that SOP has anti-inflammatory actions and protects against a variety of tissue and organ injuries. The purpose of this study was to investigate the protective effects of SOP on LPS-induced acute lung injury (ALI) in mice. Lung histological alterations, edema, and MPO activity were measured in this study. Furthermore, the production of inflammatory cytokines and the expression of NF-κB and MAPKs signaling pathways were measured. The results showed that the LPS-induced lung histological alterations, edema, protein concentration, inflammatory cell level in BALF, MDA content, and MPO activity were significantly attenuated by SOP. The LPS-induced inflammatory cytokine TNF-α, IL-1β, and IL-6 were also inhibited by SOP. SOP also inhibited the LPS-induced IL-6 and IL-8 production in A549 cells. Western blot analysis demonstrated that SOP remarkably inhibited the phosphorylation of IκBα and NF-κB. LPS-induced MAPKs activation and TLR4 expression were also suppressed by treatment with SOP. In conclusion, the results indicate that SOP protects against LPS-induced ALI by inhibiting TLR4 signaling pathway.

Keywords: Acute lung injury; LPS; TLR4; TNF-α.

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Alkaloids / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cytokines / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / immunology
  • Lung / drug effects
  • Lung / physiology*
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Sophora / immunology
  • Toll-Like Receptor 4 / metabolism

Substances

  • Alkaloids
  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • sophocarpine