Hydroxytyrosol NO regulates oxidative stress and NO production through SIRT1 in diabetic mice and vascular endothelial cells

Background: Vascular complications are major causes of disability and death in people with diabetes mellitus (DM). Nitric oxide (NO) supplement may help prevent vascular complications and is an attractive treatment option for DM. Hydroxytyrosol (HT) is a major polyphenol in olive oil. It is mainly used as a dietary supplement because of its antioxidant effect. Purpose: We aimed to determine the effects of hydroxytyrosol nitric oxide (HT-NO) on oxidative stress and NO level as well as related mechanisms. Study Design/Methods: The effects of HT-NO on oxidative stress and NO level were examined by using diabetic mouse model and HUVECs. Results: Our results showed that HT-NO has antioxidant and NO-releasing activities in vitro and in DM mice. HT-NO not only decreased blood glucose and oxidative stress but also increased NO level and deacetylase Sirtuin 1 (SIRT1) expression in DM mice and high glucose (HG)-stimulated HUVECs. Further studies found that SIRT1 activation augmented the effect of HT-NO on eNOS phosphorylation in HG-stimulated HUVECs. However, the promotive effect of HT-NO on eNOS phosphorylation was abolished by SIRT1 knockdown. Most importantly, HT-NO inhibited reactive oxygen species (ROS) production through SIRT1 in HUVECs. The ROS scavenger enhanced the effect of HT-NO on eNOS phosphorylation. Conclusion: These results suggest that HT-NO regulates oxidative stress and NO production partly through SIRT1 in DM mice and HG-stimulated HUVECs.