Hydroxysafflor Yellow a Promotes Zebrafish Cardiac Regeneration

Abstract

Regenerative medicine holds great promise for repairing damaged heart tissue and restoring cardiac function. The zebrafish (Danio rerio) has become a valuable model organism for studying heart regeneration due to its remarkable regenerative capacity. In this study, we explored the potential of hydroxysafflor yellow A (HSYA), a natural compound found in safflower, for promoting cardiac regeneration and repair in zebrafish. First, we examined the effects of HSYA on heart regeneration following cryoinjury. Histological analysis revealed that HSYA treatment significantly enhanced cardiac tissue regeneration, as indicated by increased cardiomyocyte proliferation and reduced scar formation.Additionally, we explored the molecular mechanisms underlying HSYA's regenerative effects. Gene expression profiling revealed the upregulation of key genes involved in signaling molecules and interaction and signal transduction, transporter activity, metabolic process, and organic hydroxy compound upon HSYA treatment. These findings suggest that HSYA promotes cardiac repair through multiple pathways, including stimulating estrogen and adrenergic signaling and enhancing peroxisome proliferator-activated receptor signaling. Overall, our study provides strong evidence for the potential therapeutic use of HSYA in heart regeneration. Further investigation into HSYA's mechanism of action and its application in mammalian models could pave the way for novel regenerative therapies for human heart diseases.

Note:
Funding declaration: The article was funded by the Innovation Fund for Science and Technology of Putuo District Health Commission, Shanghai (ptkwws202221).

Conflict of Interests: The authors declare no conflict of interest.

Ethical Approval: All zebrafish experiments adhered to ethical guidelines and were approved by the Institutional Animal Care and Use Committee (No. KY2023-119).

Keywords: Hydroxysafflor yellow A, cardiac regeneration, zebrafish, cryoinjury, cardiomyocyte proliferation