Artemisinin protects endothelial function and vasodilation from oxidative damage via activation of PI3K/Akt/eNOS pathway.

Abstract

Previous studies showed that artemisinin (ART) may be useful in the protection against the early development of atherosclerosis, but the effects of ART on vasodilation and eNOS remained unclear. In the current study, we investigated the protective effect of ART on endothelial cell injury induced by oxidative stress and its underlying mechanism via MTT assay, Flow Cytometry Assay, Vasodilation study, Western blotting and vivo assay. We found that pretreatment of human umbilical vein endothelial cells (HUVECs) with ART significantly suppressed H2O2-induced cell death by decreasing the extent of oxidation and MDA activity, activating SOD, increasing NO production and inhibiting caspase 3/7 activity. Meanwhile, we also found that ART was able to activate PI3K/Akt/eNOS pathway. PI3K inhibitor LY294002 or Akt kinase specific inhibitor Akt inhibitor VIII blocked the protective effect of ART. To explore the effect of ART in the damage of vasodilation induced by H2O2 in mice, we treated the aortic ring from C57BL/6 mice with H2O2 with or without ART, the results demonstrated that ART ameliorated endothelium-dependent vasodilation damage induced by H2O2. Taken together, these data suggest that ART is able to protect endothelial function and vasodilation from oxidative damage, at least in part through activation of PI3K/Akt/eNOS pathway. Our findings indicate that artemisinin maybe as a potential therapeutic agent for patients with atherosclerosis.