Single-cell analysis reveals synergistic therapeutic mechanisms of Shenqi Fuzheng formula against acute myocardial infarction

The Shenqi Fuzheng (SQ) formula, made from Codonopsis Radix (Dangshen, DS) and Astragali Radix (Huangqi, HQ), has been used in Traditional Chinese Medicine (TCM) and exhibits cardio-protective effects against acute myocardial infarction (AMI). However, the molecular basis of DS-HQ synergy remains unclear. Here, we combined RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) to explore their synergistic mechanisms. Transcriptomic analyses showed that SQ influenced the AMI network more effectively than either herb alone. ScRNA-seq analysis revealed that these synergistic effects involve both direct and indirect pro-angiogenic pathways. The combination treatment synergistically activates microvascular endothelial subpopulations and promotes angiogenesis in the border zone. It also enhances the anti-inflammatory role of a specific reparative macrophage subset and stimulates increased vascular endothelial growth factor A (VEGFA) secretion from these cells, supporting the VEGFA-VEGFR interaction between macrophages and microvascular endothelial cells. This coordinated regulation provides a plausible mechanistic explanation for the reduced infarct size and improved cardiac outcomes seen in vivo, highlighting the therapeutic value of TCM.