Lobaric acid and pseudodepsidones inhibit NF-κB signaling pathway by activation of PPAR-γ

Bioorg Med Chem. 2018 Dec 1;26(22):5845-5851. doi: 10.1016/j.bmc.2018.10.035. Epub 2018 Oct 28.

Abstract

Herein we report the anti-inflammatory activity of lobaric acid and pseudodepsidones isolated from the nordic lichen Stereocaulon paschale. Lobaric acid (1) and three compounds (2, 7 and 9) were found to inhibit the NF-κB activation and the secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in LPS-stimulated macrophages. Inhibition and docking simulation experiments provided evidence that lobaric acid and pseudodepsidones bind to PPAR-γ between helix H3 and the beta sheet, similarly to partial PPAR-γ agonists. These findings suggest that lobaric acid and pseudodepsidones reduce the expression of pro-inflammatory cytokines by blocking the NF-κB pathway via the activation of PPAR-γ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Survival / drug effects
  • Depsides / chemistry
  • Depsides / isolation & purification
  • Depsides / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Lactones / chemistry
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Lichens / chemistry*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Molecular Docking Simulation
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Salicylates / chemistry
  • Salicylates / isolation & purification
  • Salicylates / pharmacology*
  • Signal Transduction / drug effects
  • Structure-Activity Relationship
  • U937 Cells

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Depsides
  • Lactones
  • Lipopolysaccharides
  • NF-kappa B
  • PPAR gamma
  • Salicylates
  • lobaric acid