Screening and Characterization of Natural Extracts as Dual-Functional Regulators for Cardiomyocyte Regeneration and Cardiac Repair
Cardiovascular diseases (CVDs), the leading cause of global mortality, demand novel strategies to enhance cardiac regeneration. This study was designed to systematically evaluate natural extracts for their potential to enhance cardiomyocyte differentiation and facilitate cardiac repair. We performed an extensive literature review and identified 23 natural extracts associated with cardiac regeneration and stem cell differentiation. Through the use of a Tnnt2H2B-mCherry reporter mouse embryonic stem cell (mESC) line, we determined that Salvia miltiorrhiza (SM) and Ganoderma lucidum water extract (GLW) are potent inducers of cardiomyocyte differentiation. Both extracts significantly increased the proportion of beating cardiomyocytes, upregulated cardiac-specific markers (e.g., Tnnt2, Myh6), and enhanced the expression of key transcription factors (Isl1, Nkx2.5, Gata4, Mef2c) during cardiac progenitor cell (CPC) specification. Mechanistically, SM and GLW modulated the wnt signaling pathway, which is critical for CPCs specification. In vivo studies demonstrated that the treatment of SM or GLW in myocardial infarction (MI) mice improved cardiac function, as evidenced by increased ejection fraction and fractional shortening, along with enhanced proliferation of cardiomyocytes. Our findings underscore the potential of SM and GLW as promising candidates for dual-functional therapies targeting myocardial regeneration and injury mitigation, providing novel insights into natural product-based interventions for CVD management.