PUBLICATION

Pro-angiogenic activity of isoliquiritin on HUVECs in vitro and zebrafish in vivo through Raf/MEK signaling pathway

Authors
Zhang, X.H., Li, C.Y., Lin, Q.H., He, Z.H., Feng, F., He, M.F.
ID
ZDB-PUB-190317-4
Date
2019
Source
Life sciences   223: 128-136 (Journal)
Registered Authors
Keywords
HUVECs, Inhibitors, Isoliquiritin, Pro-angiogenic activity, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels/drug effects*
  • Blood Vessels/embryology
  • Cell Culture Techniques
  • Cell Survival/drug effects
  • Chalcone/analogs & derivatives*
  • Chalcone/pharmacology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/enzymology
  • Embryonic Development/drug effects*
  • Glucosides/pharmacology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mitogen-Activated Protein Kinases/metabolism
  • Neovascularization, Physiologic/drug effects*
  • Signal Transduction
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • raf Kinases/metabolism*
PubMed
30876941 Full text @ Life Sci.
Abstract
Liquorice is a widely used herbal medicine for treating various diseases native to southern Europe and parts of Asia. Isoliquiritin (ISL), a licorice root-derived flavonoid, has been reported to exhibit antioxidant, anti-inflammatory, anti-genotoxic activity and anti-depression activities. This study was aimed to explore the pro-angiogenic activity of ISL and explicate the underlying mechanism.
In vitro, ISL-treated human umbilical vein endothelial cells (HUVECs) were analyzed for cell viability, cell migration and tube formation. In vivo, pro-angiogenic effects were evaluated for the intersegmental vessels (ISVs) formation in transgenic zebrafish embryos [Tg(fli-1: EGFP)]. Furthermore, a blocking assay with eight pathways-specific kinase inhibitors were also used to determine the potential pro-angiogenic mechanism of ISL.
ISL counteracted tyrosine kinase inhibitor II (VRI)-induced endothelial cell apoptosis and promoted cell migration and tube formation in HUVECs. ISL markedly rescued ISVs loss induced by VRI in zebrafish embryos, probably by activating vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K), Raf and mitogen-activated protein kinase (MEK)-dependent signaling pathways.
Our study first discovered and confirmed the pro-angiogenic activity of ISL both in HUVECs and zebrafish. Thus, ISL could be developed as a potential therapeutic agent by the role of pro-angiogenic activity for the treatment of cardiovascular diseases, cerebrovascular diseases and other vascular diseases.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping