Silibinin ameliorats H2O2-induced cell apoptosis and oxidative stress response by activating Nrf2 signaling in trophoblast cells

Preeclampsia is a pregnancy-specific syndrome and is one of the major causes of maternal mortality around the world. Cell apoptosis and oxidative stress are involved in development of preeclampsia. Silibinin has been known with anti-inflammatory, anti-oxidative and anti-tumor roles. In this study, hydrogen peroxide (H2O2) administration induced apoptosis in HTR-8/SVneo trophoblast cells, evidenced by decreased level of Bcl-2 and increased levels of Bax and cleaved caspase-3. Western blot and JC-1 staining revealed that H2O2 led to decline of mitochondrial membrane potential (Δψm) and release of cytochrome C from mitochondria to cytoplasm. H2O2 also resulted in reactive oxygen species production and oxidative stress response, evidenced by elevated levels of malondialdehyde, and reduced activity of superoxide dismutase and glutathione peroxidase. Silibinin suppressed H2O2-induced apoptosis, decrease of Δψm and oxidative stress response. In addition, immunofluorescent staining and electrophoretic mobility shift assay demonstrated that H2O2 enhanced expression and nuclear translocation of nuclear factor-erythroid 2-like 2 (Nrf2), and the expression levels of heme oxygenases-1 and quinone oxidoreductase 1 were increased, suggesting the activation of Nrf2 signaling. The activity of Nrf2 signaling was further promoted by silibinin administration. Interestingly, the effect of silibinin on apoptosis and oxidative stress was abolished by interference RNA of Nrf2. In conclusion, we demonstrated that silibinin ameliorated H2O2-induced apoptosis and oxidative stress response by activating Nrf2 signaling in trophoblast cells. These findings may provide novel insights for treatment of preeclampsia.