Tryptanthrin Down-Regulates Oncostatin M by Targeting GM-CSF-Mediated PI3K-AKT-NF-κB Axis

Nutrients. 2024 Nov 28;16(23):4109. doi: 10.3390/nu16234109.

Abstract

Background: Oncostatin M (OSM) is involved in several inflammatory responses. Tryptanthrin (TRYP), as a natural alkaloid, is a bioactive compound derived from indigo plants. Objectives/ Methods: The purpose of this study is to investigate the potential inhibitory activity of TRYP on OSM release from neutrophils using neutrophils-like differentiated (d)HL-60 cells and neutrophils from mouse bone marrow.

Results: The results showed that TRYP reduced the production and mRNA expression levels of OSM in the granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated neutrophils-like dHL-60 cells. In addition, TRYP decreased the OSM production levels in the GM-CSF-stimulated neutrophils from mouse bone marrow. TRYP inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT, and nuclear factor (NF)-κB in the GM-CSF-stimulated neutrophils-like dHL-60 cells.

Conclusions: Therefore, these results reveal for the first time that TRYP inhibits OSM release via the down-regulation of PI3K-AKT-NF-κB axis from neutrophils, presenting its potential as a therapeutic agent for inflammatory responses.

Keywords: inflammation; neutrophils; oncostatin M; tryptanthrin.

MeSH terms

  • Animals
  • Down-Regulation* / drug effects
  • Granulocyte-Macrophage Colony-Stimulating Factor* / metabolism
  • HL-60 Cells
  • Humans
  • Mice
  • NF-kappa B* / metabolism
  • Neutrophils* / drug effects
  • Neutrophils* / metabolism
  • Oncostatin M* / metabolism
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Quinazolines* / pharmacology
  • Signal Transduction* / drug effects

Substances

  • tryptanthrine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Proto-Oncogene Proteins c-akt
  • NF-kappa B
  • Oncostatin M
  • Phosphatidylinositol 3-Kinases
  • Quinazolines