Anti‑inflammatory effects of 6‑formyl umbelliferone via the NF‑κB and ERK/MAPK pathway on LPS‑stimulated RAW 264.7 cells

Int J Mol Med. 2019 Apr;43(4):1859-1865. doi: 10.3892/ijmm.2019.4078. Epub 2019 Jan 25.

Abstract

Inhibition of over‑activated inflammation has been demonstrated as one of the most efficient strategies for treating inflammatory diseases. In the present study, 6‑formyl umbelliferone (6FU) was used to evaluate its anti‑inflammatory effects on lipopolysaccharide (LPS)‑stimulated RAW 264.7 macrophages. 6FU inhibited chronic inflammatory processes, including increasing nitric oxide levels, and the expression of pro‑inflammatory genes and producing cytokines was investigated by a nitrite assay and reverse transcription‑polymerase chain reaction, respectively. Nitric oxide and pro‑inflammatory cytokines, including tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 were decreased by treatment with 6FU, without cell cytotoxicity in LPS‑stimulated RAW 264.7 cells, which was measured by a WST‑1 assay. In the western blot analysis, the expression levels of phosphorylated extracellular signal‑regulated kinase (ERK)1/2 was downregulated in 6FU‑treated cells. Furthermore, in the western blotting and immunofluorescence staining results, translocation activities of ERK1/2 and NF‑κB from the cytoplasm to the nucleus were suppressed, which may inhibit translation of numerous proteins associated with pro‑inflammation, including inducible nitric oxide synthase and cyclooxygenase‑2. Therefore, based on these results, it was suggested that 6FU may be a potential candidate for the development of agents against chronic inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enzyme Activation / drug effects
  • Lipopolysaccharides
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Umbelliferones / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Umbelliferones
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases