Berberine, a natural lipid-lowering drug, exerts prothrombotic effects on vascular cells
Berberine, a natural lipid-lowering drug, exerts prothrombotic effects on vascular cells
复制标题
DOI：
10.1016/j.yjmcc.2008.10.011
复制
发表时间：
2009-02-01
影响因子：
5
通讯作者：
Tanner, Felix C.
中科院分区：
文献类型：
--
作者：
Holy, Erik W.;Akhmedov, Alexander;Tanner, Felix C.
小檗碱（BBR）是一种新型的天然降血脂药物。本研究探讨是否BBR，类似他汀类药物，发挥多效性作用的内皮组织因子（TF）的表达。BBR增强肿瘤坏死因子-α（TNF-α）和凝血酶诱导的人内皮细胞TF表达3.5倍。这些影响被增强的TF表面活性所抵消。相反，TF通路抑制剂的表达受损。BBR增强TNF-α诱导的TF mRNA表达，然而，TF启动子活性被抑制。ERK和p38的激活不受影响，而c-Jun末端NH 2激酶被抑制。BBR降低TF mRNA降解速率，使其半衰期从1.1小时延长至4.3小时。HMG-CoA还原酶抑制剂辛伐他汀损害凝血酶诱导的TF表达，而BBR减弱了这种抑制作用。辛伐他汀不影响TNF-α诱导的TF表达，BBR在这些条件下增强TF。给药BBR（100 mg/kg/d）可增加ApoE（-/-）小鼠颈动脉TF活性并损害TFPI表达。在临床相关浓度下，BBR通过mRNA稳定化增强TF。BBR的临床应用，无论是作为替代或与他汀类药物联合，应谨慎考虑。(C)2008年爱思唯尔公司All rights reserved.
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-a (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 NH2 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. (C) 2008 Elsevier Inc. All rights reserved.