Pro-angiogenic effects of Ilexsaponin A1 on human umbilical vein endothelial cells in vitro and zebrafish in vivo.

Abstract

BACKGROUND:

Ilexsaponin A1 is the major bioactive ingredient of Ilex pubescens Hook. et Arn. This plant has been conventionally used in Traditional Chinese Medicine for the treatment of cardiovascular diseases including stroke, coronary arterial disease, and peripheral vascular diseases.

PURPOSE:

To investigate the pro-angiogenic effect of Ilexsaponin A1 and its mechanism of action.

STUDY DESIGN:

Human umbilical vein endothelial cells (HUVECs) and transgenic zebrafish Tg(fli1:EGFP) were employed as an in vitro and in vivo model respectively.

METHODS:

Pro-angiogenic effects of Ilexsaponin A1 were examined by assessing endothelial cell proliferation, migration, invasion and tube formation. The mechanism of pro-angiogenic effects was investigated by measuring the expression level of various signalling proteins. Furthermore, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor II (VRI)-induced vascular insufficient transgenic zebrafish model was used to confirm the results of the HUVECs results in vivo.

RESULTS:

Ilexsaponin A1 significantly promoted cell proliferation, migration, invasion and tube formation in HUVECs, and rescued blood vessel loss in VRI-induced vascular insufficient zebrafish. Ilexsaponin A1 upregulated p-Akt, p-mTOR, p-Src, p-FAK, p-MEK, and p-Erk1/2 in HUVECs.

CONCLUSION:

This study showed that Ilexsaponin A1 exhibits pro-angiogenic activity in HUVECs and VRI-induced vascular insufficient zebrafish, probably by activating Akt/mTOR, MAPK/ERK and Src- and FAK-dependent signalling pathways. The findings suggest that Ilexsaponin A1 and probably I. pubescens, a major source of Ilexsaponin A1, could be developed as a potential therapeutic agent for preventing or treating cardiovascular diseases and/or other diseases related to vascular insufficiency.

• Authors: Jingjing Li, Jinming Zhang, Liang Zou, Simon Ming-Yuen Lee, Cui Yang, Sai-Wang Seto, George Pak-Heng Leung
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 36 Pg. 229-237 (Dec 01 2017) ISSN: 1618-095X [Electronic] Germany
• PMID: 29157819 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier GmbH. All rights reserved.

Chemical References

• Angiogenesis Inducing Agents
• Saponins
• enhanced green fluorescent protein
• ilexsaponin A1
• Green Fluorescent Proteins
• Mitogen-Activated Protein Kinases

Topics

• Angiogenesis Inducing Agents (pharmacology)
• Animals
• Animals, Genetically Modified
• Cell Proliferation (drug effects)
• Embryo, Nonmammalian
• Green Fluorescent Proteins (genetics)
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Mitogen-Activated Protein Kinases (metabolism)
• Neovascularization, Physiologic (drug effects)
• Saponins (pharmacology)
• Signal Transduction (drug effects)
• Zebrafish (embryology, genetics, metabolism)