Pro-angiogenic activity of astragaloside IV in HUVECs in vitro and zebrafish in vivo

Mol Med Rep. 2012 Mar;5(3):805-11. doi: 10.3892/mmr.2011.716. Epub 2011 Dec 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology*
  • Animals
  • Astragalus Plant / chemistry
  • Cell Movement
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Drugs, Chinese Herbal / chemistry
  • Gene Expression Regulation / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Indoles / pharmacology
  • Neovascularization, Physiologic / drug effects*
  • Phosphatidylinositols / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyrroles / pharmacology
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Saponins / pharmacology*
  • Triterpenes / pharmacology*
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / genetics
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism
  • Zebrafish

Substances

  • Angiogenesis Inducing Agents
  • Drugs, Chinese Herbal
  • Indoles
  • Phosphatidylinositols
  • Pyrroles
  • SH-6 compound
  • Saponins
  • Triterpenes
  • Vascular Endothelial Growth Factor A
  • astragaloside A
  • Semaxinib
  • Huang Qi
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-2
  • Proto-Oncogene Proteins c-akt