Sophoraflavanone G from Sophora alopecuroides inhibits lipopolysaccharide-induced inflammation in RAW264.7 cells by targeting PI3K/Akt, JAK/STAT and Nrf2/HO-1 pathways

Int Immunopharmacol. 2016 Sep:38:349-56. doi: 10.1016/j.intimp.2016.06.021. Epub 2016 Jun 25.

Abstract

Sophoraflavanone G (SG), a prenylated flavonoid from Sophora alopecuroides, has been reported to have many pharmacological activities including anti-inflammation. However, the molecular mechanisms of its anti-inflammatory activity remain largely unclear. In this study we investigated the effects and the underlying molecular mechanisms of SG on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. Pretreatment with SG inhibited LPS-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2) through reducing the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). SG also decreased the expressions of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), both in the protein and gene levels. Further experiments demonstrated that SG downregulated the LPS-induced upregulation of phosphorylated phosphoinositide-3-kinase and Akt (PI3K/Akt). SG also attenuated the expression of phosphorylated Janus kinase signal transducer and activator of transcription (JAK/STAT). In addition, SG upregulated heme oxygenase-1 (HO-1) expression via nuclear translocation of nuclear factor E2-related factor 2 (Nrf2). Taken together, SG may act as a natural agent to treat some inflammatory diseases by targeting PI3K/Akt, JAK/STAT and Nrf2/HO-1 pathways.

Keywords: Inflammation; LPS; RAW264.7; Sophoraflavanone G.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Flavanones / pharmacology*
  • Heme Oxygenase-1 / metabolism
  • Inflammation / drug therapy*
  • Janus Kinases / metabolism
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Membrane Proteins / metabolism
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RAW 264.7 Cells
  • STAT Transcription Factors / metabolism
  • Sophora / immunology*

Substances

  • Anti-Inflammatory Agents
  • Flavanones
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • STAT Transcription Factors
  • vexibinol
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Phosphatidylinositol 3-Kinases
  • Janus Kinases
  • Proto-Oncogene Proteins c-akt