Weirong Wang1, Chenxu Shang2, Wei Zhang3, Zhen Jin2, Feng Yao2, Yanhao He2, Bo Wang2, Yanan Li4, Jiye Zhang5, Rong Lin6. 1. Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an 710061, China; Laboratory Animal Center, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. 2. Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. 3. Department of Pharmacy, Yangquan Coalmine Group General Hospital, Yangquan 045000, China. 4. Department of Pharmacy, the First Affiliated Hospital of Xi'an Medical College, Xi'an 710061, China. 5. School of Pharmacy, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. 6. Department of Pharmacology, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China. Electronic address: linrong@xjtu.edu.cn.
Abstract
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.
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 hydroxytyrosolnitric 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 diabeticmouse model and HUVECs. RESULTS: Our results showed that HT-NO has antioxidant and NO-releasing activities in vitro and in DMmice. HT-NO not only decreased blood glucose and oxidative stress but also increased NO level and deacetylase Sirtuin 1 (SIRT1) expression in DMmice 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 DMmice and HG-stimulated HUVECs.
Authors: Marta Varela-Eirín; Paula Carpintero-Fernández; Agustín Sánchez-Temprano; Adrián Varela-Vázquez; Carlos Luis Paíno; Antonio Casado-Díaz; Alfonso Calañas-Continente; Virginia Mato; Eduardo Fonseca; Mustapha Kandouz; Alfonso Blanco; José Ramón Caeiro; María D Mayán Journal: Aging (Albany NY) Date: 2020-08-03 Impact factor: 5.955