Study on the mechanism of scutellarin's protective effect against ZEA-induced mouse ovarian granulosa cells injury

Zearalenone (ZEA), a mycotoxin produced by Fusarium, can cause reproductive disorders by targeting ovarian granulosa cells (GCs). We previous showed that scutellarin (Scu) rescues ZEA-induced GCs damage in mice. In this study, we employed iTRAQ-based proteomics to investigate the mechanism underlying the restorative effects of Scu in this model. Compared to the model group, we identified 415 differentially expressed proteins (DEPs) in both the control and Scu-treated groups, and found that these were enriched mainly in the biosynthesis and metabolism, drug metabolism, and pentose phosphate pathway. Moreover, the MAPK and heat shock protein-necroptosis pathway were implicated in regulating ZEA toxicity and the protective effect of Scu. Receptor-interacting serine threonine-protein kinase 1 (RIPK1) showed the highest fold-change in expression in the Scu-treated group. Small-interfering RNA-mediated RIPK1 knockdown further promoted the increase in cleaved-caspase-3 expression induced by ZEA, but not in the cells treated with Scu. These data indicated the involvement of multiple targets and pathways in the protective effect of Scu against ZEA-induced damage. Our findings also indicated that RIPK1 may be involved in the inhibition of GCs apoptosis induced by ZEA.