title: Pro-angiogenic activity of astragaloside IV in HUVECs in vitro and zebrafish             in vivo.
abstract: Astragaloside IV (AS-IV) is a natural product isolated from the Chinese medical herb, Radix Astragali, which has been reported to be a potential candidate for treating diseases associated with abnormal angiogenesis; however, the effect of AS-IV on angiogenesis and its underlying mechanisms are yet to be fully elucidated. In the present study, we investigated the angiogenic effect of AS-IV in vitro using human umbilical vein endothelial cells (HUVECs), and in vivo using zebrafish. AS-IV was found to stimulate the proliferation and migration of HUVECs in an XTT assay and a wound healing migration assay, respectively. Moreover, AS-IV stimulated the invasive ability of HUVECs and significantly increased the mean tube length of HUVECs in Matrigel. AS-IV induced an angiogenic response in HUVECs and enhanced mRNA expression of vascular endothelial growth factor (VEGF) and a VEGF receptor known as kinase‑domain region/fetal liver kinase-1/VEGF receptor 2 (KDR/Flk-1/VEGFR2), as well as activation of Akt as demonstrated by quantitative real-time PCR and Western blot analysis, respectively. The AS-IV-induced proliferation of HUVECs was capable of being suppressed by a KDR inhibitor (SU5416) and an Akt inhibitor (SH-6). AS-IV also rescued blood vessel loss in Tg (fli-1:EGFP) zebrafish. Altogether, our results suggest that AS-IV exerts potential pro-angiogenic effects in vitro and in vivo, and that its pro-angiogenic activity probably involves both VEGF- and Akt-dependent signaling pathways.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Hu
authors.forename: Shang
authors.initials: S
authors.lastname: Li
authors.forename: Zhen Hua
authors.initials: ZH
authors.lastname: Li
authors.forename: Che Oi
authors.initials: CO
authors.lastname: Lam
authors.forename: Si-Jia
authors.initials: SJ
authors.lastname: Hong
authors.forename: Yiu-Wa
authors.initials: YW
authors.lastname: Kwan
authors.forename: Shun Wan
authors.initials: SW
authors.lastname: Chan
authors.forename: George Pak-Heng
authors.initials: GP
authors.lastname: Leung
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D027885:Astragalus propinquus; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010716:Phosphatidylinositols / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish
chemical_list: D043925:Angiogenesis Inducing Agents; D004365:Drugs, Chinese Herbal; D007211:Indoles; D010716:Phosphatidylinositols; D011758:Pyrroles; C516024:SH-6 compound; D012503:Saponins; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; C052064:astragaloside A; C116890:Semaxinib; C027492:Huang Qi; D040262:Receptors, Vascular Endothelial Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt