Narcissin induces developmental toxicity and cardiotoxicity in zebrafish embryos via Nrf2/HO-1 and calcium signaling pathways

Narcissin is a natural flavonoid from some edible and traditional medicinal plants. It has been proven to have multiple biological functions and exhibits potential therapeutic effects on hypertension, cancer, and Alzheimer's disease. However, the toxicity of narcissin is largely unknown. Here, we revealed that narcissin treatment led to reduced hatchability, increased malformation rate, shorter body length, and slowed blood flow in zebrafish. Furthermore, bradycardia, pericardial edema, increased SV-BA distance, diminished stroke volume, ejection fraction, and ventricular short-axis shortening rate were also found. A large accumulation of ROS, increased apoptotic cells, and histopathological changes were detected in the heart region. Moreover, the gene expression profiles and molecular docking analysis indicated that Nrf2/HO-1 and calcium signaling pathways were involved in narcissin-induced toxicity. In conclusion, here we provide the first evidence that demonstrates narcissin-induced developmental toxicity and cardiotoxicity in zebrafish via Nrf2/HO-1 and calcium signaling pathways for the first time. Narcissin is a natural flavonoid from some edible and traditional medicinal plants, while its toxicity is largely unknown. Here, we revealed that narcissin treatment led to reduced hatchability, increased malformation rate, shorter body length, slowed blood flow, and cardiodevelopmental toxicity in zebrafish. A large accumulation of ROS, increased apoptotic cells, and histopathological changes were detected in the heart region. Nrf2/HO-1 and calcium signaling pathways were involved in narcissin-induced toxicity.