Stimulatory effect of Cinnamomum cassia and cinnamic acid on angiogenesis through up-regulation of VEGF and Flk-1/KDR expression
Stimulatory effect of Cinnamomum cassia and cinnamic acid on angiogenesis through up-regulation of VEGF and Flk-1/KDR expression
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DOI：
10.1016/j.intimp.2009.04.001
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发表时间：
2009-07-01
影响因子：
5.6
通讯作者：
Park, Dong-Suk
中科院分区：
文献类型：
--
作者：
Choi, Do-Young;Baek, Yong-Hyeon;Park, Dong-Suk
补充和替代医学，肉桂是已被用于改善血液循环不足引起的各种疾病的药用植物之一。然而，关于C.肉桂及其活性化合物肉桂酸（CA），尽管其具有良好的药理作用。本实验研究了川楝子乙醇提取物对小鼠抗肿瘤作用的影响。在体内基质胶塞试验中，CCE和CA剂量依赖性地增加血管性血友病因子（vWF）抗原表达和血红蛋白含量，其升高预示血管生成的开始，并且被认为是内皮活化的早期指标。在体外，CCE和CA可诱导内皮细胞增殖、迁移和形成管状结构。在HUVEC和BAEC增殖中观察到的CCE（在1或10 ng/ml的低剂量下）的25-50%增加与用CA观察到的相似。用HUVEC和BAEC观察其迁移和微管样结构效应。然而. CCE、CA和VEGF对HUVEC细胞增殖、迁移和小管样结构的影响均大于对BAEC细胞的影响。此外，CCE和CA分别诱导血管内皮细胞VEGF的生成、VEGF和与内皮细胞增殖、迁移和小管样结构相关的受体Flk-1/KDR的mRNA表达增加2.2倍和2.5倍，提示CCE及其活性化合物CA在体内外诱导血管生成，该途径与内皮细胞VEGF和Flk-1/KDR的表达有关。(C)2009爱思唯尔有限公司版权所有。
Complementary and alternative medicine, Cinnamomum cassia is one of the medicinal plants that have been used to improve various diseases caused by insufficient blood circulation. However, relatively little work has been carried out on the angiogenic responses of C. cassia and its active compound cinnamic acid (CA), despite its excellent pharmacological action. In this study, we study the effect of the ethanol extract of C. cassia (CCE) and its active compound CA, on angiogenic processes in in vitro and in vivo.In the Matrigel plug assay in vivo, CCE and CA dose dependently increased von Willebrand Factor (vWF) antigen expression, and hemoglobin contents, whose elevation paralleled the onset of angiogenesis and was considered an early indicator of endothelial activation. CCE and CA induced endothelial cells proliferation, migration and tubule-like structure in vitro. The 25-50% increase observed with CCE (at low doses of 1 or 10 ng/ml) in HUVEC and BAEC proliferation was similar to that observed with CA. The migration and tubule-like structure effect were observed with HUVEC and BAEC. However. the effect of CCE, CA and VEGF on cell proliferation, migration and tubule-like structure in HUVEC were bigger than the effect of CCE, CA and VEGF in BAEC. In addition, CCE and CA each induced 2.2-fold and 2.5-fold increases the production of VEGF, the mRNA expression of VEGF and Flk-1/KDR, the receptor involved in proliferation, migration, and tubule-like structure of endothelial cells.These data suggest that CCE and its active compound CA induce angiogenesis in vivo and in vitro, and this pathway is related with VEGF and Flk-1/KDR expression of endothelial cells. (C) 2009 Elsevier B.V. All rights reserved.