Uncovering the Targets of Pueraria Associated with Programmed Cell Death and the Construction of a Diagnostic Model in Septic Cardiomyopathy

Background: Septic cardiomyopathy (SCM) is a fatal sepsis-induced dysfunction. While Pueraria (Pue) exhibits protective effects in sepsis, its regulatory role regarding programmed cell death (PCD) in SCM remains unclear. This study aimed to identify Pue’s PCD-related targets in SCM and construct a validated diagnostic model. Methods: We analyzed 14 PCD modalities across seven GEO transcriptomic datasets. A robust machine learning framework integrating 171 algorithm combinations built a diagnostic signature. The immune landscape was profiled using single-cell RNA sequencing and enrichment analyses. Experimental validation utilized SCM patient blood samples and heart tissues from an LPS-induced murine model. Results: Nine PCD patterns were significantly altered in SCM. Intersection analysis and machine learning identified five core Pue targets: STAT3, RIPK2, GM2A, ALOX5, and DPP4. A diagnostic model constructed with these genes achieved high AUCs across all datasets. Single-cell analysis revealed cell-type-specific expression within the myocardial immune landscape. Differential expression of these five genes was validated in both human and animal samples, correlating significantly with cardiac function indices. Conclusions: Our results demonstrate that Pueraria mitigates SCM and restores cardiac function by modulating the expression of core PCD-related targets. These targets are closely associated with the localized inflammatory response, providing potential therapeutic avenues for SCM.