Gastrodin produces therapeutic effects against preeclampsia by activating Wnt 3a signaling and inhibiting ferroptosis.

Abstract

Preeclampsia (PE) is a multisystem disorder with increased maternal and perinatal mortality and morbidity while the treatment of PE remains largely unknown in clinic. Therefore, it is necessary to find more effective therapeutic methods of PE. We report herein that, Tianma Gouteng Decoction (TGD) generates protective effects against PE by activating Wnt 3a/β-catenin signaling and simultaneously suppressing ferroptosis in placental trophoblast cells. Particularly, Gastrodin (Gtd), the active component in TGD, plays a major role in protection against PE. Mechanistically, Gtd up-regulates the Wnt 3a/β-catenin signaling activity by inducing Wnt 3a mRNA expression, resulting in the increased expression of β-catenin-controlled target genes. On the other hand, Gtd-triggered Wnt activation obviously exerts negative effects on ferroptosis by promoting expression levels of the anti-ferroptosis proteins accompanied by the down-regulated reactive oxygen species (ROS) production and total iron content but the up-regulated L-Glutathione (GSH) levels. Consistently, Gtd-administration reveals apparent anti-hypertensive effects in a PE-like mouse model with diminished ferroptosis, whereas deactivation of β-catenin by administration with the specific antagonist ICG001 disrupts the protective effects derived from Gtd. Therefore, our results provide an innovative basis for the role of Gtd as a new therapy for PE.