Epimagnolin A inhibits IL-6 production by inhibiting p38/NF-κB and AP-1 signaling pathways in PMA-stimulated THP-1 cells

Environ Toxicol. 2019 Jul;34(7):796-803. doi: 10.1002/tox.22746. Epub 2019 Mar 27.

Abstract

Epimagnolin A is a lignan obtained from the flower buds of Magnolia fargesii, which is traditionally used in Asian medicine for treating headache and nasal congestion. A herbal compound fargesin obtained from M. fargesii, has exerted anti-inflammatory effects in human monocytic THP-1 cells in the previous study. The anti-inflammatory effects of epimagnolin A, however, have been not elucidated yet. In this study, it was demonstrated that epimagnolin A reduced phorbol-12-myristate-13-acetate (PMA)-induced IL-6 promoter activity and IL-6 production in human monocytic THP-1 cells. Furthermore, it was investigated the modulating effects of epimagnolin A on mitogen-activated protein kinase, nuclear factor-kappa B (NF-κB), and activator protein 1 (AP-1) activities. Phosphorylation of p38 and nuclear translocation of p50 and c-Jun were down-regulated by epimagnolin A in the PMA-stimulated THP-1 cell. The results revealed that epimagnolin A attenuated the binding affinity of NF-κB and AP-1 transcription factors to IL-6 promoter and IL-6 production through p38/NF-kB and AP-1 signaling pathways in the PMA-stimulated THP-1 cells. These results suggest that epimagnolin A can be a useful drug for the treatment of inflammatory diseases.

Keywords: Epimagnolin A; NF-κB; THP-1 cells; activator protein-1; anti-inflammatory; p38 MPAK.

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Benzodioxoles / pharmacology
  • Down-Regulation / drug effects
  • Humans
  • Interleukin-6 / metabolism*
  • Lignans / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Macrophage Activation / drug effects
  • Monocytes / drug effects
  • Monocytes / metabolism
  • NF-kappa B / metabolism*
  • Phorbol Esters / pharmacology*
  • Signal Transduction / drug effects
  • THP-1 Cells
  • Transcription Factor AP-1 / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Benzodioxoles
  • Interleukin-6
  • Lignans
  • NF-kappa B
  • Phorbol Esters
  • Transcription Factor AP-1
  • phorbol-12-myristate
  • magnolin
  • p38 Mitogen-Activated Protein Kinases
  • fargesin