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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-7940

Holy, E W; Akhmedov, A; Lüscher, T L; Tanner, F C (2009). Berberine, a natural lipid-lowering drug, exerts prothrombotic effects on vascular cells. Journal of Molecular and Cellular Cardiology, 46(2):234-240.

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Berberine (BBR) is a novel natural hypolipidemic agent. This study investigates whether BBR, similar to statins, exerts pleiotropic effects on endothelial tissue factor (TF) expression. BBR enhanced tumor necrosis factor-alpha (TNF-alpha) and thrombin induced TF expression in human endothelial cells by 3.5-fold. These effects were paralleled by an enhanced TF surface activity. In contrast, expression of TF pathway inhibitor was impaired. BBR enhanced TNF-alpha induced TF mRNA expression; however, TF promoter activity was inhibited. Activation of ERK and p38 remained unaffected, while c-Jun terminal NH(2) kinase was inhibited. BBR reduced TF mRNA degradation rates, prolonging its half-life from 1.1 to 4.3 h. The HMG-CoA reductase inhibitor simvastatin impaired thrombin induced TF expression, and BBR blunted this inhibition. Simvastatin did not affect TNF-alpha induced TF expression, and BBR enhanced TF under these conditions. Administration of BBR (100 mg/kg/d) increased TF activity and impaired TFPI expression in carotid artery of ApoE(-/-) mice. BBR enhances TF via mRNA stabilization at clinically relevant concentrations. Clinical application of BBR, either as an alternative to or in combination with statins, should be considered with caution.


22 citations in Web of Science®
25 citations in Scopus®
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64 downloads since deposited on 05 Jan 2009
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:February 2009
Deposited On:05 Jan 2009 14:42
Last Modified:05 Apr 2016 12:42
Funders:Swiss National Science Foundation, Velux Foundation, Wolfermann Nägeli Foundation, Swiss Heart Foundation
Publisher DOI:10.1016/j.yjmcc.2008.10.011
Related URLs:http://www.sciencedirect.com/science/journal/00222828 (Publisher)
PubMed ID:19014947

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