title: Berberine improves endothelial function by reducing endothelial microparticles-mediated oxidative stress in humans.
abstract: BACKGROUND
  Circulating endothelial microparticles (EMPs) lead to endothelial dysfunction by increasing oxidative stress. Berberine has a beneficial effect on endothelial function, but no data are available on the EMP-mediated oxidative stress. The present study tests the hypothesis that berberine contributes to the improvement of endothelial function in humans via inhibiting EMP-mediated oxidative stress in vascular endothelium.
  
  
  METHODS
  Twelve healthy subjects received a 1-month berberine therapy and eleven healthy subjects served as control. Endothelium-dependent and -independent function in the brachial artery was assessed by flow-mediated vasodilation (FMD) and sublingual nitroglyceride-mediated vasodilation (NMD). Circulating EMPs and serum malondialdehyde (MDA) were measured before and after therapy. Furthermore, in vitro human umbilical vein endothelial cells (HUVECs) were stimulated by EMPs with or without presence of anti-oxidant compound apocynin or berberine. Intracellular reactive oxygen species (ROS), nitric oxide (NO) production and NADPH oxidase 4 (Nox4) protein expressions were examined, respectively.
  
  
  RESULTS
  The levels of serum MDA and circulating CD31+/CD42- MPs were significantly reduced in the berberine group compared with the control group, which were associated with improvement of FMD. The EMPs in vitro facilitated ROS production and Nox4 protein expression and reduced NO synthesis in HUVECs. These alterations can be reversed by the presence of apocynin or berberine, respectively.
  
  
  CONCLUSIONS
  The present study demonstrated for the first time that EMP-induced upregulation of Nox4 expression may enhance ROS production in HUVECs. Berberine treatment contributes to the amelioration of endothelial function through a partially reducing oxidative stress of vascular endothelium induced by circulating CD31+/CD42- microparticles in humans.
authors.affiliation: Department of Hypertension and Vascular Disease, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Su
authors.forename: Fang
authors.initials: F
authors.lastname: Wu
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Xia
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Bing-Bo
authors.initials: BB
authors.lastname: Yu
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Qiu
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
mesh_terms: D001599:Berberine / Q000494:pharmacology*; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D001599:Berberine; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human