Luteolin Alleviates the TNF- α-Induced Inflammatory Response of Human Microvascular Endothelial Cells via the Akt/MAPK/NF- κ B Pathway

Mediators Inflamm. 2024 Dec 11:2024:6393872. doi: 10.1155/mi/6393872. eCollection 2024.

Abstract

Endothelial dysfunction and pathological alterations are pivotal in the pathogenesis of cardiovascular disease. To date, effective interventions for these endothelial changes are lacking. Tumor necrosis factor-alpha (TNF-α) is known to significantly contribute to these alterations. It has been reported the potential of luteolin to mitigate TNF-α-induced inflammation, yet its specific mechanisms and targets still remain to be elucidated. This study aims to investigate the effects and mechanisms of luteolin on TNF-α-induced inflammatory injury in human microvascular endothelial cells, thereby advancing the understanding of luteolin's medicinal properties. Our findings demonstrate that luteolin notably inhibits TNF-α-induced phosphorylation of Akt, mitogen activated protein kinase (MAPK), and the nuclear factor-kappaB (NF-κB) p65. It significantly reduces the transcriptional activity of NF-κB p65 and AP-1 and decreases the expression of mRNA and proteins related to adhesion molecules and inflammatory mediators. Additionally, luteolin inhibited the reduction in STAT3 phosphorylation. In conclusion, luteolin effectively suppresses TNF-α-induced inflammatory injury in endothelial cells via the Akt/MAPK/NF-κB pathway.

Keywords: TNF-α; endothelial cells; inflammation; luteolin; signal pathways.

MeSH terms

  • Endothelial Cells* / drug effects
  • Endothelial Cells* / metabolism
  • Humans
  • Inflammation* / metabolism
  • Luteolin* / pharmacology
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B* / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Luteolin
  • Tumor Necrosis Factor-alpha
  • Proto-Oncogene Proteins c-akt
  • NF-kappa B
  • Mitogen-Activated Protein Kinases