An active component containing pterodontic acid and pterodondiol isolated from Laggera pterodonta inhibits influenza A virus infection through the TLR7/MyD88/TRAF6/NF‑κB signaling pathway

Mol Med Rep. 2018 Jul;18(1):523-531. doi: 10.3892/mmr.2018.8947. Epub 2018 May 2.

Abstract

The influenza virus is a pathogen that can cause pandemic and epidemic outbreaks, and therefore represents a severe threat to human health. Antiviral drugs have an important role in the prevention and treatment of influenza, although the increasing emergence of drug resistance has given rise to a requirement for the development of novel antiviral drugs. In the present study, an active component (C8) isolated from Laggera pterodonta was evaluated. The nuclear magnetic resonance spectroscopy and mass spectrometry analysis results revealed that two eudesmane‑type sesquiterpene compounds were identified in C8; pterodontic acid and pterodondiol. C8 was demonstrated to have a broad‑spectrum effect against different influenza viruses, including human and avian influenza viruses, with a half maximal inhibitory concentration value of 19.9‑91.4 µg/ml. The antiviral mechanisms of C8 were further clarified. Western blot analysis verified that C8 inhibited Toll‑like receptor 7, myeloid differentiation primary response protein 88 and tumor necrosis factor (TNF) receptor associated factor 6 expression, in addition to p65 phosphorylation, at a concentration of 100 or 150 µg/ml. An indirect immunofluorescence assay demonstrated that C8 may inhibit p65/NF‑κB nuclear translocation. Additionally, C8 prevented an increase in cytokine mRNA expression, including interleukin (IL)‑1β, IL‑6, IL‑8 and C‑C motif chemokine 2 (MCP‑1). Furthermore, the Bio‑Plex assay results indicated that the protein expression of IL‑6, IL‑8, TNF‑α, C‑X‑C motif chemokine 10, MCP‑1 and C‑C motif chemokine 5 was inhibited. These findings suggest that C8 has the potential to be developed into an anti‑inflammatory drug for the prevention and treatment of influenza A virus infection.

MeSH terms

  • A549 Cells
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Asteraceae / chemistry
  • Cell Line
  • Dogs
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology*
  • Humans
  • Influenza A virus / drug effects*
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Sesquiterpenes / therapeutic use
  • Signal Transduction / drug effects*
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / metabolism

Substances

  • Antiviral Agents
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Sesquiterpenes
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 7
  • pterodondiol
  • pterodontic acid