Cornin, a compound from Verbena officinalis L, ameliorates preeclampsia progression through activating NO signaling...

Preeclampsia (PE) is a common gestational disorder with high morbidity and mortality. There is currently no effective treatment for PE in clinic. Therefore, it is necessary to find a more effective treatment scheme.

Extra-villous TEV-1 cells, EA. hy926 cells, and human induced pluripotent stem cells (hiPSC)-derived vascular organoids in vitro, different PE-like mouse models in vivo, a zebrafish model in vivo, and human placenta tissues as well as isolated primary cytotrophoblasts (CTBs) were used in this study.

We show herein that Cornin exerts protective effects against PE by activating the nitric oxide synthase 2/nitric oxide (NOS2/NO) signaling and suppressing the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling in both cultured trophoblasts and mouse placentas. Mechanistically, Cornin increases the stability of NOS2 by directly binding to ARG-536 of NOS2, while simultaneously, the interaction between NOS2 and NFκB is promoted, followed by the phosphorylation and activation of NOS2 as well as the dephosphorylation at Ser-536 and inactivation of NFκB. Ultimately, NO production is increased and inflammation is suppressed, accompanied by the reduced reactive oxygen species (ROS) levels, enhanced angiogenesis, and decreased expression of NFκB-directed target genes. Consistently, Cornin administration alleviates pregnant outcomes in PE mouse models.

Collectively, our results provide an innovative basis for Cornin to intervene in the development of PE and ameliorate PE outcomes.