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

Year: 2020

Authors: Martini D., Pucci C., Gabellini C., Pellegrino M., Andreazzoli M.

Autors Affiliation: Univ Pisa, Dept Biol, Cell & Dev Biol Unit, SS12 Abetone & Brennero, I-56127 Pisa, Italy; St Anna Sch Adv Studies, Pisa, Italy; CNR, Natl Inst Opt, Pisa, Italy; Univ Pisa, Interdept Res Ctr Nutrafood Nutraceut Food Hlth, Pisa, Italy; Catholic Univ, Inst Genom Med, I-00168 Rome, 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

More Information: We thank Prof Renata Batistoni for the gift of berberine and for helpful discussion, Prof Franco Cotelli for providing the transgenic Tg(kdrl:EGFP)S843/roya9/a9;nacrew2/w2 casper zebrafish line , Dr Letizia Pitto and Dr Elena Guzzolino for cmlc2, bmp4 and notch1b plasmids and technical advices. This work was supported by local funding of the University of Pisa (ex 60%) to M.A.
KeyWords: TUMOR-INDUCED ANGIOGENESIS; VASCULAR DEVELOPMENT; CARDIAC DEVELOPMENT; EMBRYOID BODIES; IN-VIVO; EXPRESSION; VEGF;TOXICITY; GROWTH; METAANALYSIS
DOI: 10.1038/s41598-020-73661-5

Citations: 13
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