Protective role of metformin in preeclampsia via the regulation of NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways by activating AMPK

• DOI: 10.1016/j.placenta.2023.10.003
• Publication Date: 2023-10-17T15:46:38Z
• Authors: Lidan He; Xiuyan Wu; Feng Zhan; Xuemei Li; Jianbo Wu
• Keywords: Viability assay; MTT assay

Preeclampsia (PE) is a pregnancy complication that leads to hypertension and proteinuria and causes maternal mortality. Metformin (MET) is an oral hypoglycemic agent that activates AMPK-regulated signaling pathways and inhibits inflammation and oxidative stress responses. This study explored MET's roles and molecular mechanisms in PE.The protein or mRNA expression of signaling pathways and inflammation-related genes were detected by Western blotting and RT-qPCR and cell viability was analyzed with MTT. In addition, flow cytometry was used to assess apoptosis, and mitochondrial membrane potential was detected using JC-1 staining with flow cytometry. Moreover, LDH Cytotoxicity Assay Kit detected the release of LDH, and ROS, MDA, or SOD kits detected oxidative stress-related factors.MET significantly inhibited inflammatory damage and oxidative stress responses in LPS-induced HTR-8/SVneo cells. Besides, MET could activate AMPK and then affect NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways in LPS-induced HTR-8/SVneo cells. Compound C (an AMPK inhibitor) significantly reversed MET's effects on LPS-stimulated HTR-8/SVneo cells.MET attenuated inflammatory and oxidative stress of HTR-8/SVneo cells in PE by activating AMPK to regulate NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways, suggesting that MET was a potential therapeutic drug for PE.