Astragalus membranaceus ‐Derived Carbon Dots Nanozymes Ameliorate Myocardial Ischemia–Reperfusion Injury via Combined Pharmacological Action and Antioxidant Catalysis

Myocardial ischemia-reperfusion injury (MIRI) remains a major obstacle to functional recovery after myocardial infarction, primarily driven by excessive reactive oxygen species (ROS) generation, mitochondrial dysfunction, and apoptosis. In this study, we developed a straightforward hydrothermal method to synthesize Astragalus membranaceus-derived carbon dots (AM-CDs), using this medicinal herb, known for its cardiovascular protective effects, as a biomass precursor. The resulting AM-CDs exhibited broad-spectrum ROS-scavenging activity and pronounced biological effects against oxidative stress, inflammation, and apoptosis. In vitro experiments revealed that AM-CDs restored mitochondrial membrane potential and reduced DNA damage, as indicated by decreased γ-H2AX expression. Furthermore, AM-CDs downregulated pro-inflammatory cytokine mRNA expression in LPS-stimulated macrophages. In a rat model of MIRI, direct intramyocardial administration of AM-CDs resulted in a significant reduction in infarct size, improved left ventricular ejection fraction and fractional shortening in a dose-dependent manner, and exhibited no notable systemic toxicity. Transcriptomic and protein analyses further demonstrated that AM-CDs downregulate pro-apoptotic proteins and modulate the PI3K-AKT and NF-κB-apoptosis signaling pathways, thereby disrupting the vicious cycle of oxidative stress, inflammation, and cell death. Collectively, these findings indicate that AM-CDs offer a promising therapeutic approach that integrates traditional medicine with nanotechnology to provide effective cardioprotection against MIRI.