PUBLICATION

Pro-angiogenic activity of Tongnao decoction on HUVECs in vitro and zebrafish in vivo

Authors
Wang, J., Zhang, X.H., Xu, X., Zhu, Q., Yao, B., Liang, S., Chen, Z., Wang, Y., He, M.F., Wu, M.
ID
ZDB-PUB-200403-7
Date
2020
Source
Journal of ethnopharmacology   254: 112737 (Journal)
Registered Authors
Keywords
Chinese herbal decoction, HUVECs, Inhibitors, Pro-angiogenic activity, Tongnao decoction, Zebrafish
MeSH Terms
  • Angiogenesis Inducing Agents/pharmacology*
  • Animals
  • Animals, Genetically Modified
  • Blood Vessels/drug effects
  • Cell Movement/drug effects
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Cells, Cultured
  • Embryo, Nonmammalian/blood supply
  • Human Umbilical Vein Endothelial Cells/drug effects
  • Human Umbilical Vein Endothelial Cells/physiology
  • Humans
  • Wound Healing/drug effects
  • Zebrafish
PubMed
32147480 Full text @ J. Ethnopharmacol.
Abstract
Tongnao Decoction (TND) is a Chinese decoction approved and used in Jiangsu Province Hospital for the treatment of ischemic stroke. It shows conclusive efficiency in the improvement of neurologic impairment and activities of daily living of the patients.
Recently, angiogenesis has been recognized as a potential therapeutic strategy for treating cerebral ischemia. This study was aimed to provide comprehensive evidence for the pro-angiogenic effect of TND and characterize the underlying mechanism.
We firstly established the chemical fingerprinting of TND. Then, the in vitro pro-angiogenic activities of TND were tested on human umbilical vein endothelial cells (HUVECs) through cell viability, wound healing and tube formation assays. The in vivo pro-angiogenic effects were evaluated on transgenic zebrafish embryos [Tg (fli-1: EGFP)] through the formation of intersegmental vessels (ISVs), subintestinal vessels (SIVs) and central arteries (CtAs). Lastly, the potential mechanisms of TND were analyzed by a blocking assay with eight pathways-specific kinase inhibitors.
TND promoted the proliferation, migration and tube formation of HUVECs. TND also rescued the impairment of ISVs, SIVs and CtAs caused by VRI in a dose-dependent manner in zebrafish embryos. TND could activate vascular endothelial growth factor receptor-2 (VEGFR-2), phosphoinositide 3-kinase (PI3K) - protein kinase B (Akt) and Raf - mitogen-activated protein kinase1/2 (MEK1/2) - extracellular regulated kinase 1/2 (ERK1/2) signaling pathways.
Our study firstly demonstrated the pro-angiogenic activities of TND. Our work provided evidences for the clinical usage of TND in restoring neurovascular function through promoting angiogenesis in the ischemic cerebral microvascular.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping