title: Cinnamaldehyde prevents endothelial dysfunction induced by high glucose by activating Nrf2.
abstract: OBJECTIVE
  It is well documented that hyperglycemia-induced oxidative stress is an important causative factor of endothelial dysfunction. Cinnamaldehyde (CA) is a key flavor compound in cinnamon essential oil that can enhance the antioxidant defense against reactive oxygen species (ROS) by activating NF-E2-related factor 2 (Nrf2), which has been shown to have a cardiovascular protective effect, but its role in endothelial dysfunction induced by high glucose is unknown.
  
  
  METHODS
  Dissected male C57BL/6J mouse aortic rings and HUVECs were cultured in normal glucose(NG 5.5 mM) or high glucose(HG 30.0 mM) DMEM treatment with or without CA (10 µM).
  
  
  RESULTS
  Treatment with CA protected the endothelium relaxation, inhibited ROS generation and preserved nitric oxide (NO) levels in the endothelium of mouse aortas treated with high glucose . CA up-regulated Nrf2 expression, promoted its translocation to the nucleus'and increased HO-1, NQO1, Catalase and Gpx1 expression under high glucose condition. The increased level of nitrotyrosine in HUVECs under high glucose was also attenuated by treatment with CA. Dihydroethidium (DHE) and DAF-2DA staining indicated that CA inhibited the ROS generation and preserved the NO levels in HUVECs, but these effects were reversed by Nrf2-siRNA in high glucose conditions.
  
  
  CONCLUSIONS
  Our results indicated that CA protected endothelial dysfunction under high glucose conditions and this effect was mediated by Nrf2 activation and the up-regulation of downstream target proteins. CA administration may represent a promising intervention in diabetic patients who are at risk for vascular complications.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Pu
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Peijian
authors.initials: P
authors.lastname: Wang
authors.forename: Dengpan
authors.initials: D
authors.lastname: Liang
authors.forename: Qiulin
authors.initials: Q
authors.lastname: Wang
authors.forename: Yonghe
authors.initials: Y
authors.lastname: Hu
authors.forename: Binghu
authors.initials: B
authors.lastname: Li
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Hao
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000171:Acrolein; D005947:Glucose; C012843:cinnamaldehyde