Farrerol inhibits IL-6 and IL-8 production in LPS-stimulated human gingival fibroblasts by suppressing PI3K/AKT/NF-κB signaling pathway

Arch Oral Biol. 2016 Feb:62:28-32. doi: 10.1016/j.archoralbio.2015.11.007. Epub 2015 Nov 12.

Abstract

Objectives: Farrerol, a new type of 2,3-dihydro-flavonoid isolated from rhododendron, has been shown to have anti-bacterial and anti-inflammatory activities. In the present study, we investigated the anti-inflammatory effects of farrerol on the production of IL-6 and IL-8 in human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS).

Methods: The cytotoxicity of farrerol was determined using the MTT assay. The production of IL-6 and IL-8 was measured using ELISA and qRT-PCR. The effects of farrerol on PI3K, Akt phosphorylation, and NF-κB activation were detected using western blotting analyses.

Results: These results showed that farrerol inhibited LPS-induced IL-6 and IL-8 production in a dose dependent manner. LPS-induced NF-κB activation was suppressed by farrerol. Furthermore, farrerol suppressed LPS-induced PI3K and Akt phosphorylation, which are upstream molecules of NF-κB.

Conclusion: These results indicated that farrerol attenuated IL-6 and IL-8 production by inhibition of PI3K and AKT phosphorylation, resulting in an inhibition of NF-κB activation. Farrerol may be a therapeutic agent for the treatment of periodontal disease.

Keywords: Farrerol; Human gingival fibroblasts; IL-6; NF-κB; PI3K.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Inflammatory Agents / pharmacology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chromones / pharmacology*
  • Fibroblasts / drug effects*
  • Gingiva / cytology
  • Gingiva / drug effects*
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / antagonists & inhibitors*
  • Interleukin-8 / biosynthesis
  • Lipopolysaccharides / pharmacology*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Periodontal Diseases / therapy
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects

Substances

  • Anti-Bacterial Agents
  • Anti-Inflammatory Agents
  • Chromones
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • Phosphoinositide-3 Kinase Inhibitors
  • farrerol