In hyperglycemic conditions, levels of precursors of triose phosphate, such as glucose or fructose, are increased. After nonenzymatic fragmentation, high serum levels of MGO were observed in patients with either type 1 or type 2 diabetes. MGO as one of the most reactive dicarbonyls, is considered to be an important glycating agent to consider for glycation damage to the mitochondrial proteome. Moreover, the cytotoxicity of MGO is mediated by the modification of deoxyribonucleic acid and activation of apoptosis. Vascular disorders will induce several biochemical and cellular reactions such as inflammatory response, increased reactive oxygen species production, impairment of blood brain barrier and calcium overload. Edaravone, the first clinical drug of neuroprotection for ischemic stroke patients in the world, is used for the purpose of aiding neurological recovery following acute brain ischemia and subsequent cerebral infarction. In a recent study, edaravone has been proved to modulate endothelial barrier properties via the activation of S1P1 and a downstream signaling pathway. These findings provide new insights for edaravone as an effective therapeutic agent for diseases with systemic vascular endothelial disorders such as diabetes stroke. The present study was aimed to demonstrate the protective effect of edaravone on MGO-induced injury in the cultured human brain microvascular endothelial cells and accompanied by identifying the possible mechanism which is responsible for the protection. What’s more, the protective effect of edaravone was also investigated in MGO enhancing oxygenglucose deprivation induced injury. Data derived from the present study raise the possibility that edaravone may be a new strategy to prevent or improve vascular complications associated with diabetes stroke. In the present study, we demonstrated that MGO induced injury was associated with AGEs accumulation, enhancing RAGE expression and ROS release in the cultured HBMEC, which were alleviated by pretreatment of edaravone. Furthermore, MGO enhanced OGD-induced cell injury which was also protected by edaravone. It is well known that diabetes gain high serum levels of glucose or fructose-precursors of triose phosphate which would augment MGO AbMole Diniconazole formation by Maillard reaction. The dicarbonyl compound MGO is involved in a variety of detrimental processes under hyperglycemic conditions. In the present study, we provided evidence that MGO alone could induce the cultured HBMEC damage. MGO increases glycation of mitochondrial proteins which is associated with increased formation of ROS and increased proteome damage by oxidative and nitrosative processes. Edaravone has been reported to display the advantageous effects by protecting against oxidative stress on ischemic stroke both in animals and clinical trials. Notably, the effect of edaravone on diabetic cerebrovascular injury is still unclear. Our present work indicated that MGO-induced injury in the cultured HBMEC could be suppressed by edaravone treatment. In the AbMole Nitisinone development of diabetic complications, MGO reacted on and modified cellular proteins to form cross-links of amino groups, and then generates AGEs. To gain further insight into the mechanism, the temporal changes in AGEs protein levels following MGO treatment were addressed. Our results demonstrated that AGEs accumulation significantly increased after 24 h MGO treatment which was consistent with our previous reports. Intriguingly, edaravone could decrease AGEs accumulation, which was known to impair cellular function by increasing cellular oxidative stress on binding to their specific cell surface receptors, such as RAGE and galectin-3.