The natural compound puerarin alleviates inflammation and apoptosis in experimental cell and rat preeclampsia models

Puerarin (Pue), an isoflavone derived from Radix puerariae, exerts anti-apoptosis and anti-inflammatory effects. However, the protective effect of Pue on PE is still unknown. The present study aimed to investigate whether Pue alleviates symptoms of PE and suppresses inflammation and apoptosis in vitro and in vivo. A cell model of PE was established by exposing HTR8/SVneo cells to LPS and an RNA-SEQ study was performed in LPS-stimulated HTR8/SVneo cells. We also established a rat model of PE by injecting pregnant rats with LPS and the basic preeclamptic symptoms were evaluated. Additionally, the placental histology, placental inflammation cytokines, and apoptosis markers were also measured. Pue protected HTR8/SVneo cells from LPS-evoked cytotoxicity, decreased the levels of sFlt-1, ET-1, and tPA in HTR8/SVneo cells. RNA-SEQ results revealed the significant changes in the expression levels of hub genes (TNF, IL-6, Jun, and NFKBIA) related to multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, inflammatory disease, and NF-κB signaling pathway. After administration of Pue, we observed that LPS-evoked PE symptoms (hypertension, proteinuria, and fetal growth restriction), were reversed. Besides, Pue improved placental pathology change and reducing placental sFlt-1, ET-1, and tPA mRNA expression. Abnormal placental inflammatory cytokines (TNF, IL-6, IFN-γ, and IL-4) and apoptosis markers (Bcl-2, Bax, caspase-3, caspase-8, and caspase-9) expressions in the LPS-treated group were reversed after Pue treatment. Our findings revealed that Pue plays beneficial roles in PE models, and therefore possesses the therapeutic potential for prevention and treatment of PE.