Identification of mundoserone by zebrafish in�vivo screening as a natural product with anti‑angiogenic activity

Abstract

The present study aimed to screen natural products with anti-angiogenic potential from the Natural Products Collection of MicroSource. The anti-angiogenic activity of 240 natural products was assessed using the zebrafish line Tg(fli1a: EGFP)y1. At 24 h post-fertilization, the embryos were treated with the library compounds for 24 h and, the morphology of the intersegmental vessels (ISVs) was then assessed using a fluorescence microscope, followed by counting of ISVs and calculation of the inhibition ratio. The expression of angiogenesis-associated genes was determined by quantitative polymerase chain reaction. The results indicated that mundoserone inhibited ISV formation in zebrafish embryos in a dose-dependent manner, with a significant anti-angiogenic activity observed at a concentration of 10 µM, leading to an ISV inhibition ratio of 73.6±1.3%. Mundoserone significantly reduced the expression of slit guidance ligand 3 (SLIT3), roundabout guidance receptor 1 (ROBO1) and −2, fibroblast growth factor receptor (FGFR)2 and −3, as well as protein tyrosine phosphatase, receptor type B (PTP-RB), but increased the expression of NOTCH1A. Accordingly, mundoserone may be an effective angiogenic inhibitor, which acts via downregulation of SLIT/ROBO1 and FGFR/PTP-RB, and upregulation of NOTCH1A signaling.

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

“…13 Besides, the anti-angiogenic activity of Mundoserone has been reported in our previous study. 14 In this study, we used zebrafish strain Tg (fli1a:EGFP) y1 as the in vivo model for screening of natural products because of its high genetic, pharmacologic and physiologic similarity with humans. Besides, the zebrafish is usually small, optical transparency and produces a large number of embryos.…”

“…12 Among the screened compounds, five compounds, dihydromunduletone, deoxysappanone B 7,4ʹ-Dimethyl Ether (Deox B 7,4), Mundoserone, ononetin, and pomiferin, were identified to have potential anti-angiogenic activity on the zebrafish embryogenesis. Since the anti-angiogenic activity of dihydro-munduletone and mundoserone has been reported in previous studies, 13,14 we focused on the anti-angiogenic activity of Deox B 7,4 on the zebrafish embryos in this study. qRT-PCR was used to examine the expression pattern of various genes that regulate angiogenesis in the zebrafish embryos treated with Deox B 7,4.…”

Transcriptional regulation in model organisms: recent progress and clinical implications

“…zebrafish Zebrafish as experimental models, in addition to being used for screening of drug targets, such as screening natural products with anti-angiogenesis potential, are often used to study some molecular mechanisms; for example, in a zebrafish model, researchers found that the thymus cells Foxn1 by MCM2 maintain thymic epithelial cells and T-cell development and help to control the opening of important genes [25][26][27].…”

“…Recently, a research team used the zebrafish model to evaluate the anti-angiogenic drug mundoserone. The researchers found that mundoserone could inhibit zebrafish blood vessel formation by downregulating SLIT3/ROBO1 and FGFR/PTP-RB, as well as upregulating NOTCH1A [25].…”

“…Xylose isomerase can reduce the activity of neurons that produce the neurotransmitter octopamine, which inhibits the movement of fruit flies [22–24]. zebrafishZebrafish as experimental models, in addition to being used for screening of drug targets, such as screening natural products with anti-angiogenesis potential, are often used to study some molecular mechanisms; for example, in a zebrafish model, researchers found that the thymus cells Foxn1 by MCM2 maintain thymic epithelial cells and T-cell development and help to control the opening of important genes [25–27]. mouseMice are widely used in experiments because they are mammals like humans and many mechanisms of the human body are also present in mice.…”