The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo
The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo
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DOI：
10.1002/jcb.21403
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Lee, Simon Ming-Yuen
中科院分区：
文献类型：
--
作者：
Lam, Hio-Wa;Lin, Hui-Chao;Lee, Simon Ming-Yuen
血管生成在伤口愈合和胎儿发育等一系列生理过程中发挥着重要作用。许多疾病都与血管生成调节的不平衡有关，要么是血管生成过度，要么是血管生成不足。当归（Angelica sinensis， AS）常用于中药处方中，是治疗此类疾病的潜在候选者。然而，AS对血管生成的生物学作用及其机制尚未完全阐明。本研究描述了芦笋提取物在体外对人内皮细胞（HUVEC）和斑马鱼体内的血管生成作用。XTT法和显微镜下细胞计数证实提取物对HUVEC有促进作用；此外，流式细胞术分析表明，提取物增加了S期HUVEC的百分比。伤口愈合迁移实验表明，在AS提取物处理的HUVEC中可以测量到迁移的急剧增加。同时，黄芪提取物处理组侵染细胞数和平均管长均显著增加。该提取物还被证明可以促进斑马鱼肠下血管（SIVs）的变化，这是血管生成的一个特征。实时荧光定量PCR检测发现，紫菀提取物可增强血管内皮生长因子（VEGF） mRNA的表达。在基于珠的免疫分析中，与对照细胞相比，在积液中也观察到更高水平的p38和JNK 1/2表达。上述结果表明，当归提取物具有促进血管生成的作用，其作用机制可能与p38和JNK 1/2磷酸化有关。
Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. Many diseases are associated with imbalances in regulation of angiogenesis, in which it is either excessive or there is insufficient blood vessel formation. Angelica sinensis (AS), commonly used in the prescriptions of Chinese medicine, is a potential candidate for curing such diseases. However, biological effects of AS on angiogenesis and underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of AS extract on human endothelial cells (HUVEC) in vitro and zebrafish in vivo. The extract was demonstrated, by XTT assay and microscopic cell counting, to stimulate the proliferation of HUVEC; in addition, flow cytometry analysis indicated that the extract increased the percentage of HUVEC in the S phase. The wound healing migration assay illustrated that a dramatic increase in migration could be measured in AS extract-treated HUVEC. Meanwhile, the number of invaded cells and the mean tube length were significantly increased in AS extract treatment groups. The extract was also demonstrated to promote changes in subintestinal vessels (SIVs) in zebrafish, one feature of angiogenesis. In addition, AS extract was found by real-time PCR to enhance vascular endothelial growth factor (VEGF) mRNA expression. In a bead-based immunoassay, higher levels of p38 and JNK 1/2 expression were also observed in effusions compared with control cells. All results suggest that Angelica sinensis extract can promote angiogenesis, and that the angiogenic effects involve p38 and JNK 1/2 phosphorylation.