Luteolin prevents TNF-α-induced NF-κB activation and ROS production in cultured human placental explants and endothelial cells.

INTRODUCTION

Preeclampsia (PE) is a serious hypertensive pregnancy disorder and a leading cause of maternal and perinatal morbidity and mortality. Despite the prevalence and complications, there are no approved therapeutics to relieve PE symptoms. Inflammation, oxidative stress, and angiogenic imbalance have been shown to contribute to the PE pathophysiology, though there is a lack of understanding in how best to target these pathways in PE. We recently demonstrated that the bioflavonoid luteolin is a potent inhibitor of the anti-angiogenic and pro-hypertensive soluble fms-like tyrosine kinase 1 (sFlt-1), and here we aimed to determine if luteolin was also capable of reducing inflammation and oxidative stress pathways.

METHODS

Tumor necrosis factor (TNF)-α, which is upregulated in PE, was utilized to stimulate these pathways in human placental explants and endothelial cells. Endothelin-1 (ET-1) and interleukin (IL)-6 in the media from explants and cells were measured via ELISA, and NF-κB localization and reactive oxygen species were detected via fluorescence microscopy.

RESULTS

Pretreatment with luteolin demonstrated significant reductions in NF-κB activation, reactive oxygen species, superoxide, and IL-6 and ET-1 expression in endothelial cells. We also saw a significant reduction in phosphorylation of NF-κB in human placental explants.

DISCUSSION

These data demonstrate that luteolin inhibits pathways implicated in the development of PE and should be explored further for its potential as a PE therapeutic.