Objective:To investigate the protective effect and underlying mechanism(s) of icariin (ICA) in preventing hydrogen peroxide (H2O2)-induced vascular endothelial cell injury via endoplasmic reticulum stress (ERS).Methods:To study the effects of ICA on H2O2-induced damage,we used the cell counting kit-8 assay to detect cell viability and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay to determine cell adhesion and apoptosis,respectively.Spectrophotometry and enzyme-linked immunosorbent assay were used to measure the expression levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).Subsequently,glucose-regulated protein 78 (GRP78),activating transcription factor-4 (ATF4) and eukaryotic initiation factor-2α (eIF2α) were detected using West blotting.Results:In human umbilical vein endothelial cells,different concentrations of ICA exhibited multiple effects,including reduced H2O2 damage,improved cell viability and adhesion,reduced cell apoptosis and increased SOD and GSH-Px activity.Among the ICA concentrations used,only the H2O2 + 100 μmol/L ICA group had significant differences compared to the H2O2 group.ERS activators H2O2 and DL-dithiothreitol (DTT) significantly increased GRP78,ATF4 and elF2α expressions,decreased cell activity and reduced SOD and GSH-Px activity.In contrast,the H2O2+ 100μmol/L ICA and H2O2 + 100 μmol/L ICA+ DTT groups had significant inhibitory effects on the expressions of GRP78,ATF4 and eIF2α proteins,showing enhanced cell viability and SOD and GSH-Px activity.Conclusion:The results showed the dose-dependent effects of ICA against H2O2-induced injury in vascular endothelial cells.The inhibition of GRP78,ATF4 and eIF2α protein expressions in the ERS,and the subsequent alleviation of oxidative stress damage,might be the molecular mechanism.