PUBLICATION

Exposure to the natural alkaloid Berberine affects cardiovascular system morphogenesis and functionality during zebrafish development

Authors
Martini, D., Pucci, C., Gabellini, C., Pellegrino, M., Andreazzoli, M.
ID
ZDB-PUB-201020-28
Date
2020
Source
Scientific Reports   10: 17358 (Journal)
Registered Authors
Andreazzoli, Massimiliano
Keywords
none
MeSH Terms
  • Animals
  • Berberine/toxicity*
  • Cardiovascular System/embryology*
  • Morphogenesis/drug effects*
  • Teratogens/toxicity
  • Zebrafish/embryology*
PubMed
33060638 Full text @ Sci. Rep.
Abstract
The plant-derived natural alkaloid berberine displays therapeutic potential to treat several pathological conditions, including dyslipidemias, diabetes and cardiovascular disorders. However, data on berberine effects during embryonic development are scarce and in part controversial. In this study, using zebrafish embryos as vertebrate experimental model, we address the effects of berberine treatment on cardiovascular system development and functionality. Starting from the observation that berberine induces developmental toxicity and pericardial edema in a time- and concentration-dependent manner, we found that treated embryos display cardiac looping defects and, at later stages, present an abnormal heart characterized by a stretched morphology and atrial endocardial/myocardial detachment. Furthermore, berberine affected cardiac functionality of the embryos, promoting bradycardia and reducing the cardiac output, the atrial shortening fraction percentage and the atrial stroke volume. We also found that, during development, berberine interferes with the angiogenic process, without altering vascular permeability. These alterations are associated with increased levels of vascular endothelial growth factor aa (vegfaa) mRNA, suggesting an important role for Vegfaa as mediator of berberine-induced cardiovascular defects. Altogether, these data indicate that berberine treatment during vertebrate development leads to an impairment of cardiovascular system morphogenesis and functionality, suggesting a note of caution in its use during pregnancy and lactation.
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
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Orthology
Engineered Foreign Genes
Mapping