Toluhydroquinone from Aspergillus sp. suppress inflammatory mediators via nuclear factor-κB and mitogen-activated protein kinases pathways in lipopolysaccharide-induced RAW264.7 cells

J Pharm Pharmacol. 2015 Sep;67(9):1297-305. doi: 10.1111/jphp.12421. Epub 2015 Apr 23.

Abstract

Objectives: The purpose of this study is to investigate anti-inflammatory effects of toluhydroquinone in lipopolysaccharide (LPS)-stimulated RAW264.7 cells.

Methods: Toluhydroquinone was purified from a fungal strain, Aspergillus sp. We investigated that levels of nitric oxide (NO) using Griess reagent, production of prostaglandin E2 (PGE2 ) and pro-inflammatory cytokines using ELISA assay. We conducted Western blot analysis to investigate regulatory effects of toluhydroquinone on expression of inducible nitric oxide synthase (iNOS), cyclooxyganse-2 (COX-2), nuclear factor-κB (NF-κB), Akt and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW264.7 cells. The translocation of NF-κB was detected by immunofluorescence staining.

Key findings: Toluhydroquinone inhibited production of NO and PGE2 via suppressing protein expression of iNOS and COX-2, respectively. Secretion and expression of inflammatory cytokines were down-regulated by toluhydroquinone as well. Toluhydroquinone reduced phosphorylation of Akt, NF-κB and MAPKs. Moreover, toluhydroquinone inhibited translocation of NF-κB from the cytosol into the nucleus.

Conclusions: We revealed that inhibitory effects of toluhydroquinone on expression of inflammatory mediators are induced through inactivation of Akt, NF-κB and MAPKs. Thus, our results suggest that toluhydroquinone may be used for a potential anti-inflammatory reagent.

Keywords: MAPKs; NF-κB; RAW264.7 cells; anti-inflammatory effects; toluhydroquinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Aspergillus / metabolism*
  • Benzoquinones / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • HEK293 Cells
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Benzoquinones
  • Lipopolysaccharides
  • NF-kappa B
  • Nitric Oxide
  • quinone
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases
  • Dinoprostone