Endothelial protective effects of ferulic acid in preeclampsia treatment

Preeclampsia (PE) is a complex gestational disorder marked by vascular abnormalities and elevated blood pressure yet remains without widely effective treatments. This study investigates the efficacy of ferulic acid (FA) in alleviating PE symptoms by targeting the signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) signaling axis to enhance endothelial integrity and reduce inflammation. An N^G-nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced PE mouse model was used, with FA administration to pregnant mice to assess therapeutic effects on key outcomes such as blood pressure, proteinuria, and placental function. Single-cell RNA sequencing (scRNA-seq) and molecular assays were conducted to examine FA's impact on endothelial cell balance, inflammation, and pathway-specific activity. The results showed that FA treatment significantly reduced hypertension, proteinuria, and inflammation, while improving endothelial cell balance in PE mice. In addition, inhibition of STAT3 phosphorylation by FA enhanced endothelial barrier function, stabilized vascular integrity, and supported improved fetal development outcomes. Overall, these findings demonstrate the protective effects of FA in PE by alleviating endothelial impairment and dampening inflammatory activity, offering a promising strategy to improve maternal and fetal health in PE, with implications for managing pregnancy-related vascular dysfunctions.NEW & NOTEWORTHY Our study investigates ferulic acid (FA) as a potential therapeutic intervention for preeclampsia (PE), a severe pregnancy complication with limited treatment options. By targeting the STAT3/VEGF signaling pathway, FA demonstrated significant reductions in hypertension, inflammation, and improved endothelial cell balance in PE mice. These results highlight FA's promise in enhancing maternal and fetal health by addressing endothelial dysfunction, suggesting its potential for broader applications in managing pregnancy-related vascular dysfunctions.