title: Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase.
abstract: OBJECTIVE
  Endothelial dysfunction is a key event that links obesity, diabetes, hypertension, and cardiovascular diseases. The aim of the present study was to examine the protective effect of the alkaloid drug berberine against hyperglycemia-induced cellular injury and endothelial dysfunction.
  
  
  RESULTS
  In both cultured endothelial cells and blood vessels isolated from rat aorta, berberine concentration dependently enhanced phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 and promoted the association of eNOS with heat shock protein 90 (HSP90), leading to an increased production of nitric oxide. Furthermore, berberine attenuated high glucose-induced generation of reactive oxygen species, cellular apoptosis, nuclear factor-kappaB activation, and expression of adhesion molecules, thus suppressing monocyte attachment to endothelial cells. In mouse aortic rings, berberine elicited endothelium-dependent vasodilatations and alleviated high glucose-mediated endothelial dysfunction. All these beneficial effects of berberine on the endothelium were abolished by either pharmacological inhibition of adenosine monophosphate-activated protein kinase (AMPK) or adenovirus-mediated overexpression of a dominant negative version of AMPK.
  
  
  CONCLUSIONS
  Berberine protects against endothelial injury and enhances the endothelium-dependent vasodilatation, which is mediated in part through activation of the AMPK signalling cascade. Berberine or its derivatives may be useful for the treatment and/or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.
authors.affiliation: Department of Medicine, University of Hong Kong, L8-40, New Laboratory Block, 21 Sassoon Road, Hong Kong, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Karen S L
authors.initials: KS
authors.lastname: Lam
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Wing Tak
authors.initials: WT
authors.lastname: Wong
authors.forename: Hongying
authors.initials: H
authors.lastname: Ye
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Lau
authors.forename: Paul M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D001599:Berberine; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D055372:AMP-Activated Protein Kinases