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

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.