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.
Autors Affiliation: Cell and Developmental Biology Unit, Department of Biology, University of Pisa, SS12 Abetone e Brennero,
56127 Pisa, Italy; Sant’Anna School of Advanced Studies, Pisa, Italy; National Institute of Optics, National
Research Council, Pisa, Italy; Interdepartmental Research Center Nutrafood “Nutraceuticals and Food for Health”,
University of Pisa, Pisa, Italy.
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.
Journal/Review: SCIENTIFIC REPORTS
Volume: 10 (1) Pages from: 17358 to: 17358
KeyWords: TUMOR-INDUCED ANGIOGENESIS; VASCULAR DEVELOPMENT; CARDIAC DEVELOPMENT; EMBRYOID BODIES; IN-VIVO; EXPRESSION; VEGF;TOXICITY; GROWTH; METAANALYSISDOI: 10.1038/s41598-020-73661-5