title: Dietary curcumin ameliorates aging-related cerebrovascular dysfunction through the AMPK/uncoupling protein 2 pathway.
abstract: OBJECTIVE
  Age-related cerebrovascular dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2) plays a crucial role in regulating reactive oxygen species (ROS) production. Dietary patterns are widely recognized as contributors to cardiovascular and cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related cerebrovascular dysfunction via UCP2 up-regulation.
  
  
  METHODS
  The 24-month-old male rodents used in this study, including male Sprague Dawley (SD) rats and UCP2 knockout (UCP2-/-) and matched wild type mice, were given dietary curcumin (0.2%). The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were observed by immunoblotting.
  
  
  RESULTS
  Dietary curcumin administration for one month remarkably restored the impaired cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice.
  
  
  CONCLUSIONS
  Curcumin improves aging-related cerebrovascular dysfunction via the AMPK/UCP2 pathway.
authors: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing, China.
authors: Yunfei
authors: Y
authors: Pu
authors: Hexuan
authors: H
authors: Zhang
authors: Peijian
authors: P
authors: Wang
authors: Yu
authors: Y
authors: Zhao
authors: Qiang
authors: Q
authors: Li
authors: Xing
authors: X
authors: Wei
authors: Yuanting
authors: Y
authors: Cui
authors: Jing
authors: J
authors: Sun
authors: Qianhui
authors: Q
authors: Shang
authors: Daoyan
authors: D
authors: Liu
authors: Zhiming
authors: Z
authors: Zhu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D003474:Curcumin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2; D014664:Vasodilation / Q000187:drug effects
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D003474:Curcumin