PUBLICATION
Pro-angiogenic effects of Ilexsaponin A1 on human umbilical vein endothelial cells in vitro and zebrafish in vivo
- Authors
- Li, J., Zhang, J., Zou, L., Lee, S.M., Yang, C., Seto, S.W., Leung, G.P.
- ID
- ZDB-PUB-171122-6
- Date
- 2017
- Source
- Phytomedicine : international journal of phytotherapy and phytopharmacology 36: 229-237 (Journal)
- Registered Authors
- Keywords
- Endothelial cells, Ilex pubescens, Ilexsaponin A1, Pro-angiogenesis, Zebrafish
- MeSH Terms
-
- 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
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 29157819 Full text @ Phytomedicine
Citation
Li, J., Zhang, J., Zou, L., Lee, S.M., Yang, C., Seto, S.W., Leung, G.P. (2017) Pro-angiogenic effects of Ilexsaponin A1 on human umbilical vein endothelial cells in vitro and zebrafish in vivo. Phytomedicine : international journal of phytotherapy and phytopharmacology. 36:229-237.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping