In vivo Screening of Natural Products Against Angiogenesis and Mechanisms of Anti-Angiogenic Activity of Deoxysappanone B 7,4ʹ-Dimethyl Ether
| Autor: | Yuqi Fan, Kan Chen, Chengyu Mao, Changqian Wang, Jun Gu, Huasu Zeng, Zhihua Han |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pharmacology education.field_of_study Delta-like ligand 4 biology Chemistry Fibroblast growth factor receptor 1 Pharmaceutical Science Protein tyrosine phosphatase biology.organism_classification Molecular biology Green fluorescent protein 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Fibroblast growth factor receptor 030220 oncology & carcinogenesis embryonic structures Drug Discovery Signal transduction education Receptor Zebrafish |
| Zdroj: | Drug Design, Development and Therapy. 14:3069-3078 |
| ISSN: | 1177-8881 |
| DOI: | 10.2147/dddt.s252681 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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