<p>In vivo Screening of Natural Products Against Angiogenesis and Mechanisms of Anti-Angiogenic Activity of Deoxysappanone B 7,4ʹ-Dimethyl Ether</p>

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 7.4ʹ-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.

Identification of mundulone and mundulone acetate as natural products with tocolytic efficacy in mono- and combination-therapy with current tocolytics

“…In vitro therapeutic index obtained by measuring compound`s cytotoxicity is commonly used to quantify the extent of the safety at the desired efficacious conditions of a single-or combination of compounds. The toxicity of mundulone has been previously reported on HEK293 cells and zebrafish embryo [64,65], however, mundulone acetate's toxicity is not reported. In the current study, mundulone by itself was found to be toxic at low concentrations (TI = 0.8).…”

The Role of SLIT3–ROBO4 Signaling in Endoplasmic Reticulum Stress–Induced Delayed Corneal Epithelial and Nerve Regeneration

“…In multiple studies on angiogenesis, it has been reported that there is a SLIT3-ROBO4 pathway. 50 , 59 – 61 Studies in vascular endothelial cells have shown that ligand SLIT3 inhibits ROBO4 shedding to enhance ROBO4 signaling. 62 In the present study, we found that the increased expression of SLIT3 and ROBO4 induced by TG were significantly inhibited by SLIT3-specific siRNA, indicating that TG induced ER stress enhanced ROBO4 expression by SLIT3.…”

Ethanol extract from Artemisia argyi leaves inhibits HSV-1 infection by destroying the viral envelope

“…However, the two flavones had never been isolated before, and their biological functions remain to be clarified. Interestingly, analogs of the two flavones, deoxysappanone B 7,4′-dimethyl ether, deoxysappanone B 7,3′-dimethyl ether acetate, and 5,7-dihydroxy-3′,4′-dimethoxyflavone have been demonstrated to have anti-cryptosporidial [ 25 ], anti-angiogenic [ 26 ] or antibacterial [ 27 ] activity. Therefore, isolation and purification of the two new flavones from AEE to determine whether they have similar antibacterial or antiviral activities are needed in the future.…”