Prevention properties on cerebral ischemia reperfusion of medicine food homologous Dioscorea yam-derived diosgenin based on mediation of potential targets

•Diosgenin (DIO) derived from MFH Dioscorea yams reveals excellent anti-I/R effects.•Potential targets of DIO against I/R are firstly uncovered with proteomics approach.•BICD2, HNRNPK, CEP41, PPM1K, and ARL2BP targets are validated in vivo and in vitro.•This paper suggests consumption of Dioscorea yams benefit from protection of I/R. I/R (cerebral ischemia reperfusion injury) is the secondary complication of ischemic stroke patients that are immediately treated with drug thrombolysis or vascular recanalization in clinic. Diosgenin (DIO) purified from medicine food homologous (MFH) Dioscorea yam source is served as a fatal starting material to synthesize multifarious steroidal anti-inflammatory drugs in medicinal field, and has previously been demonstrated the potential prevention of I/R. However, the detailed mechanisms of neuroprotective effects against I/R remain elusively understood. Here, a global proteomic dynamics of rat right hemisphere brains was executed to investigate the protein expression patterns with a quantitative LC-MSn. In total, 5043 proteins were identified and 418 ones were determined to be significantly dysregulated DEPs (differentially expressed proteins) in comparison of Sham verse I/R and I/R verse DIO after onset stage of I/R, among which 5 DEPs namely BICD2, HNRNPK, CEP41, PPM1K, and ARL2BP, whose biological functions were mainly clustered into the mediation of nervous system, were selected for further validation in vitro and in vivo, and the change tendency expectedly supported the proteomic findings. Additionally, the AUC value of the combined ROC of these 5 DEPs was 0.988 with P