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Cardiovascular Research Advance Access first published online on February 27, 2009
This version [Corrected Proof] published online on March 19, 2009

Cardiovascular Research, doi:10.1093/cvr/cvp078
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Berberine prevents hyperglycemia-induced endothelial injury and enhances vasodilatation via adenosine monophosphate-activated protein kinase and endothelial nitric oxide synthase

Yiqun Wang1,{dagger}, Yu Huang4,{dagger}, Karen S.L. Lam1,3, Yiming Li5, Wing Tak Wong4, Hongying Ye5,{dagger}, Chi-Wai Lau4, Paul M. Vanhoutte2,3 and Aimin Xu1,2,3,*

1 Department of Medicine, University of Hong Kong, L8-40, New Laboratory Block, 21 Sassoon Road, Hong Kong
2 Department of Pharmacology, University of Hong Kong, Hong Kong
3 Research Center for Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong, Hong Kong
4 Department of Physiology, Institute of Vascular Medicine, Chinese University of Hong Kong Hong Kong
5 Division of Endocrinology, Hua Shan Hospital, Fudan University, Shanghai, China

* Corresponding author. Tel: +86 852 2819 9754; fax: +86 852 2816 2095.E-mail address: 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 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-{kappa}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 adenosine monophosphate-activated protein kinase (AMPK) or adenovirus-mediated overexpression of a dominant negative version of AMPK.

Conclusion: 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.

KEYWORDS Endothelium; Nitric oxide; Hyperglycemia; Vascular injury; Oxidative stress


Time for primary review: 19 days

{dagger} The first two authors contribute equally to the study.


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