Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells
Asiaticoside Inhibits TNF-α-Induced Endothelial Hyperpermeability of Human Aortic Endothelial Cells
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DOI：
10.1002/ptr.5404
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发表时间：
2015-10-01
影响因子：
7.2
通讯作者：
Zuraini, Ahmad
中科院分区：
文献类型：
--
作者：
Fong, Lai Yen;Ng, Chin Theng;Zuraini, Ahmad
内皮渗透性的增加通常在各种病理条件下促进水肿形成。肿瘤坏死因子-α（TNF-alpha）是一种促动脉粥样硬化细胞因子，在动脉粥样硬化早期损害内皮屏障功能，导致内皮功能障碍。积雪草苷是从积雪草中提取的一种三萜类化合物，具有抗炎活性。为了研究积雪苷在保护内皮屏障中的作用，我们评估了其对人主动脉内皮细胞（HAEC）中TNF-α引起的内皮通透性过高和肌动蛋白丝破坏的影响。TNF-α导致内皮细胞对异硫氰酸荧光素（FITC）-葡聚糖的通透性增加。积雪苷预处理显著抑制TNF-α诱导的通透性增加。积雪苷还通过抑制应力纤维的形成来防止TNF-α诱导的肌动蛋白重新分布。然而，增加的F到G肌动蛋白的比例刺激TNF-α并没有改变积雪苷。细胞松弛素D是一种肌动蛋白解聚剂，用于将积雪苷的抗高通透性作用与肌动蛋白细胞骨架联系起来。令人惊讶的是，积雪苷未能防止细胞松弛素D诱导的通透性增加。这些结果表明，积雪苷对TNF-α引发的内皮屏障破坏和肌动蛋白重排没有显着变化的总肌动蛋白池。然而，积雪苷似乎通过其他机制来维持内皮屏障的完整性，而不是稳定F-肌动蛋白组织。版权所有（c）2015约翰威利父子有限公司
The increase in endothelial permeability often promotes edema formation in various pathological conditions. Tumor necrosis factor-alpha (TNF-alpha), a pro-atherogenic cytokine, impairs endothelial barrier function and causes endothelial dysfunction in early stage of atherosclerosis. Asiaticoside, one of the triterpenoids derived from Centella asiatica, is known to possess antiinflammatory activity. In order to examine the role of asiaticoside in preserving the endothelial barrier, we assessed its effects on endothelial hyperpermeability and disruption of actin filaments evoked by TNF-alpha in human aortic endothelial cells (HAEC). TNF-alpha caused an increase in endothelial permeability to fluorescein isothiocyanate (FITC)-dextran. Asiaticoside pretreatment significantly suppressed TNF-alpha-induced increased permeability. Asiaticoside also prevented TNF-alpha-induced actin redistribution by suppressing stress fiber formation. However, the increased F to G actin ratio stimulated by TNF-alpha was not changed by asiaticoside. Cytochalasin D, an actin depolymerizing agent, was used to correlate the anti-hyperpermeability effect of asiaticoside with actin cytoskeleton. Surprisingly, asiaticoside failed to prevent cytochalasin D-induced increased permeability. These results suggest that asiaticoside protects against the disruption of endothelial barrier and actin rearrangement triggered by TNF-alpha without a significant change in total actin pool. However, asiaticoside seems to work by other mechanisms to maintain the integrity of endothelial barrier rather than stabilizing the F-actin organization. Copyright (c) 2015 John Wiley & Sons, Ltd.