Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 27, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp078
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via AMP-activated protein kinase and eNOS
1 Department of Medicine, University of Hong Kong
2 Department of Pharmacology, University of Hong Kong
3 Research Center for Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong
4 Institute of Vascular Medicine and Department of Physiology, Chinese University of Hong Kong
5 Division of Endocrinology, Hua Shan Hospital, Fudan University, Shanghai, China
* Address correspondence to Aimin Xu, Department of Medicine, The University of Hong Kong, L8-40, New Laboratory Block, 21 Sassoon Road, Hong Kong. Tel: 852 28199754; Fax: 852 28162095. Email: amxu{at}hkucc.hku.hk
Aims: 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.
Methods and 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 (HSP) 90, leading to an increased production of nitric oxide (NO). Furthermore, berberine attenuated high glucose-induced generation of reactive oxygen species (ROS), cellular apoptosis, nuclear factor-
B 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 AMP-activated protein kinase, 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 signaling cascade. Berberine or its derivatives may be useful for the treatment and/or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.
Time for primary review: 19 Days
W.Y and H.Y contribute equally to this work.
![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
J. Xu and M.-H. Zou Molecular Insights and Therapeutic Targets for Diabetic Endothelial Dysfunction Circulation, September 29, 2009; 120(13): 1266 - 1286. [Full Text] [PDF] |
||||
