Cimifugin Inhibits Inflammatory Responses of RAW264.7 Cells Induced by Lipopolysaccharide

Med Sci Monit. 2019 Jan 14:25:409-417. doi: 10.12659/MSM.912042.

Abstract

BACKGROUND RAW264.7 cells are induced by lipopolysaccharide (LPS) as a rheumatoid arthritis (RA) model. The present study investigated the effect of cimifugin on the proliferation, migration, chemotaxis, and release of inflammation-related factors and inflammation-related signaling pathways of LPS-induced RAW264.7 cells. MATERIAL AND METHODS MTS assay was used to determine the proliferation of RAW264.7 cells. Transwell assay was employed to examine the migration and chemotaxis of the cells. ELISA was performed to measure the contents of chemotactic factors and inflammatory factors in cell culture supernatants. Western blotting was carried out to detect the expression of factors related with MAPKs and NF-κB signaling pathways. RESULTS Cimifugin (0-100 mg/L) had no cytotoxicity for RAW264.7 cells. LPS stimulation induced morphological differentiation of RAW264.7 cells, but intervention by cimifugin inhibited the activation effect by LPS by about 50%. Cimifugin (100 mg/L) decreased the migration and chemotaxis of RAW264.7 cells to 1/3 of that in control cells by decreasing the release of migration- and chemotaxis-associated factors by at least 30%. Cimifugin (100 mg/L) suppressed the release of inflammatory factors from RAW264.7 cells to less than 60% of that in the LPS group. In addition, cimifugin (100 mg/L) inhibited the activities of MAPKs and NF-κB signaling pathways. CONCLUSIONS The present study demonstrates that cimifugin reduces the migration and chemotaxis of RAW264.7 cells and inhibits the release of inflammatory factors and activation of related signaling pathways induced by LPS. Cimifugin may have potential pharmacological effects against RA.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Cell Movement / drug effects
  • Chromones / pharmacology*
  • Chromones / toxicity
  • Cyclooxygenase 2 / metabolism
  • Inflammation / drug therapy*
  • Lipopolysaccharides / pharmacology
  • Macrophages / metabolism
  • Mice
  • Models, Biological
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells / drug effects
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Chromones
  • Lipopolysaccharides
  • NF-kappa B
  • cimifugin
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2