PUBLICATION
In vivo Screening of Natural Products Against Angiogenesis and Mechanisms of Anti-Angiogenic Activity of Deoxysappanone B 7,4'-Dimethyl Ether
- Authors
- Chen, K., Fan, Y., Gu, J., Han, Z., Zeng, H., Mao, C., Wang, C.
- ID
- ZDB-PUB-200818-12
- Date
- 2020
- Source
- Drug design, development and therapy 14: 3069-3078 (Journal)
- Registered Authors
- Keywords
- 4สน-dimethyl ether, angiogenesis, delta-like ligand 4, deoxysappanone B 7, natural products, protein tyrosine phosphatase, receptor type B, slit guidance ligand/roundabout guidance receptor
- MeSH Terms
-
- Angiogenesis Inhibitors/therapeutic use*
- Animals
- Biological Products/therapeutic use*
- Chromones/therapeutic use*
- Drug Evaluation, Preclinical
- Guaiacol/analogs & derivatives*
- Guaiacol/therapeutic use
- Humans
- Neovascularization, Pathologic/drug therapy*
- Zebrafish/embryology
- PubMed
- 32801645 Full text @ Drug Des Devel Ther
Citation
Chen, K., Fan, Y., Gu, J., Han, Z., Zeng, H., Mao, C., Wang, C. (2020) In vivo Screening of Natural Products Against Angiogenesis and Mechanisms of Anti-Angiogenic Activity of Deoxysappanone B 7,4'-Dimethyl Ether. Drug design, development and therapy. 14:3069-3078.
Abstract
Introduction The aim of this study was to screen the leading compounds of natural origin with anti-angiogenic potential and to investigate their anti-angiogenic mechanism preliminarily.
Materials and methods An initial screening of 240 compounds from the Natural Products Collection of MicroSource was performed using the transgenic zebrafish strain Tg [fli1a: enhanced green fluorescent protein (EGFP)]y1 . The zebrafish embryos at 24 h post-fertilization were exposed to the natural compounds for an additional 24 h; then, morphological changes in the intersegmental vessels (ISVs) were observed and quantified under a fluorescence microscope. The expression profiles of angiogenesis-related genes in the zebrafish embryos were detected using quantitative real-time PCR.
Results Five compounds were identified with potential anti-angiogenic activity on the zebrafish embryogenesis. Among them, deoxysappanone B 7.4'-dimethyl ether (Deox B 7,4) showed anti-angiogenic activity on the formation of ISVs in a dose-dependent manner. The inhibition of ISV formation reached up to 99.64% at 5 μM Deox B 7,4. The expression of delta-like ligand 4 (dll4), hes-related family basic helix-loop-helix transcription factor with YRPW motif 2, ephrin B2, fibroblast growth factor receptor (fgfr) 3, cyclooxygenase-2, protein tyrosine phosphatase, receptor type B (ptp-rb), phosphoinositide-3-kinase regulatory subunit 2, slit guidance ligand (slit) 2, slit3, roundabout guidance receptor (robo) 1, robo2, and robo4 were down-regulated, while vascular endothelial growth factor receptor-2, fgfr 1, and matrix metallopeptidase 9 were up-regulated in the zebrafish embryos treated with Deox B 7,4.
Conclusion Deox B 7,4 has a therapeutic potential for the treatment of angiogenesis-dependent diseases and may exert anti-angiogenic activities by suppressing the slit2/robo1/2, slit3/robo4, cox2/ptp-rb/pik3r2, and dll4/hey2/efnb2a signaling pathways as well as activation of vegfr-2/fgfr1/mmp9.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping