Advanced oxidation protein products (AOPPs), as a novel indicator of oxidative stress, are thought to be involved in agingrelated diseases.The excessive AOPPs were served as independent risk factor for coronary artery disease (CAD), atherosclerosis and carotid intima media thickness, which mainly through hypoxia inducible factor1t (HIF1 α) and vascular endothelial growth factor (VEGF) pathway.Paeoniflorin, a monoterpene glycoside, exerts well protective effect in vascular as its good antioxidant property.However, there is no research that has reported whether Paeoniflorin has the protective effect on oxidative damage induced by AOPPs in HUVECs, and also it is little known about this underlying mechanism.The protective effect of Paeoniflorin on oxidative darnage induced by AOPPs was investigated in HUVECs.The cell viability was assessed by MTT colorimetric assay.The fluorescence intensity of2′, 7′dichlorofluoresceindiacetate (DCFHDA) staining was detected for intracellular reactive oxygen species(ROS) production.And mitochondrial membrane potential (MMP) was measured byflow cytometry and confocal microscopy staining with Mito Tracker(R) Deep Red/ MitoTracker(R) Green.The intracellular adenosine triphosphate(ATP) was measured by ATP Determination Kit.Nox2, Nox4, HIF1α, VEGF and NFκB p65 protein expressions were detected by western blot.The results showed that AOPPs significantly decreased MMP and ATP in a dosedependent manner.Furthermore, AOPPs increased HIF1α, VEGF protein expression, and also partly increased NFκB p65 expression may through increase of ROS production by upregulations of Nox2, Nox4 and RAGE expression in HUVECs.These effects were remarkably reversed by pretreatment of Paeoniflorin, which indicated that Paeoniflorin inhibited Nox2/Nox4 expression, restored ATP depletion and mitochondria dysfunction via ROS suppression, and downregulated HIF1α/VEGF possibly via ROSNFκB axis.In conclusion, these results suggesting that Paeoniorin had a protective effect against AOPPinduced oxidative damage in HUVECs and that HIF1α/VEGF might be intervention site in this process.