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.
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.
|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
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||05 Jan 2009 15:42|
|Last Modified:||23 Nov 2012 15:42|
|Funders:||Swiss National Science Foundation, Velux Foundation, Wolfermann Nägeli Foundation, Swiss Heart Foundation|
|Related URLs:||http://www.sciencedirect.com/science/journal/00222828 (Publisher)|
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