Suppression of angiogenesis by the plant alkaloid, sanguinarine
Suppression of angiogenesis by the plant alkaloid, sanguinarine
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DOI：
10.1016/j.bbrc.2004.03.077
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发表时间：
2004-04-30
影响因子：
3.1
通讯作者：
Koh, GY
中科院分区：
文献类型：
--
作者：
Eun, JP;Koh, GY
血根碱是一种从加拿大血根中提取的苯并苯胺类生物碱。它的主要药理学用途是在牙科产品中，它具有抗菌、抗真菌和抗炎活性，可以减少牙龈炎症和牙龈上菌斑的形成。血管生成是炎症不可缺少的，而大多数血管生成依赖于血管内皮生长因子（VEGF）。然而，血根碱对血管生成的影响尚不清楚。在本研究中，我们研究了血根碱对vegf诱导的血管生成的体外和体内作用。有趣的是，在纳摩尔浓度下，血根碱以剂量依赖的方式显著抑制vegf诱导的内皮细胞迁移、发芽和体外存活。此外，血根碱还能有效抑制小鼠基质塞和鸡胚绒毛膜尿囊膜的血管形成。我们的生化实验表明，血根碱强烈抑制基础和vegf诱导的Akt磷酸化，而对vegf诱导的ERK1/2和PLCgammal的激活没有任何影响。因此，我们得出结论，血根碱是一种有效的抗血管生成天然产物，其作用方式可能涉及阻断vegf诱导的Akt激活。因此，除了抗菌、抗真菌和抗炎活性外，血根碱还具有新的抗血管生成作用。(C) 2004爱思唯尔公司版权所有。
Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinaria canadensis. Its principal pharmacologic use is in dental products where it has antibacterial, antifungal, and anti-inflammatory activities that reduce gingival inflammation and supragingival plaque formation. Angiogenesis is indispensable for inflammation, and most angiogenesis is dependent on vascular endothelial growth factor (VEGF). However, the effect of sanguinarine on angiogenesis is not known. In the present study, we examined the effect of sanguinarine on VEGF-induced angiogenesis in vitro and in vivo. Interestingly, sanguinarine markedly suppressed VEGF-induced endothelial cell migration, sprouting, and survival in vitro in a dose-dependent manner at nanomolar concentrations. Furthermore, sanguinarine potently suppressed blood vessel formation in vivo in mouse Matrigel plugs and the chorioallantoic membrane of chick embryos. Our biochemical assays indicated that sanguinarine strongly suppressed basal and VEGF-induced Akt phosphorylation, while it did not produce any changes in VEGF-induced activation of ERK1/2 and PLCgammal. Therefore, we conclude that sanguinarine is a potent antiangiogenic natural product, and its mode of action could involve the blocking of VEGF-induced Akt activation. Thus, in addition to antibacterial, antifungal, and anti-inflammatory activities, sanguinarine has a novel antiangiogenic role. (C) 2004 Elsevier Inc. All rights reserved.