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

Area of Science:

• Developmental Biology
• Cardiovascular Biology
• Pharmacology

Background:

• Berberine, a plant alkaloid, shows therapeutic promise for metabolic and cardiovascular diseases.
• Limited and conflicting data exist on berberine's effects during embryonic development.
• Zebrafish embryos serve as a vertebrate model to investigate developmental impacts.

Purpose of the Study:

• To investigate the effects of berberine on cardiovascular system development and function in zebrafish embryos.
• To determine the concentration- and time-dependency of berberine-induced developmental toxicity.
• To elucidate the molecular mechanisms underlying berberine's cardiovascular teratogenicity.

Main Methods:

• Zebrafish embryos were exposed to varying concentrations of berberine.
• Cardiovascular morphology and cardiac looping were assessed.
• Cardiac function parameters (heart rate, cardiac output, stroke volume) were measured.
• Angiogenesis and vascular permeability were evaluated.
• Vascular endothelial growth factor aa (vegfaa) mRNA levels were quantified.

Main Results:

• Berberine induced developmental toxicity and pericardial edema in a dose- and time-dependent manner.
• Cardiac looping defects and abnormal heart morphology (stretched, atrial detachment) were observed.
• Berberine treatment resulted in bradycardia, reduced cardiac output, and impaired atrial contractility.
• Angiogenesis was disrupted, but vascular permeability remained unaffected.
• Increased vegfaa mRNA levels suggest its role in mediating berberine's cardiovascular effects.

Conclusions:

• Berberine impairs cardiovascular system development and function in vertebrate embryos.
• The observed defects are linked to altered angiogenesis and elevated vegfaa expression.
• Caution is advised regarding berberine use during pregnancy and lactation due to potential teratogenic effects.