Systematic Identification of Active Compounds in Yiqi Huoxue Granule and Their Therapeutic Mechanisms against Atherosclerosis

Background Yiqi Huoxue Granule (YQHX), a traditional Chinese medicine formula, is widely used for the treatment of atherosclerotic diseases, including coronary heart disease and arrhythmias. However, its active components and molecular mechanisms remain unclear. Methods The active components of YQHX were identified using UPLC-Q-Exactive Orbitrap-MS. Potential therapeutic targets and mechanisms against atherosclerosis (AS) were systematically predicted through network pharmacology and molecular docking analyses. The effects of YQHX on atherosclerotic plaque formation and associated mechanisms were further validated in ApoE ^⁻/⁻ mice. Results A total of 36 absorbable compounds were identified in the serum of rats following YQHX administration, and 252 potential therapeutic targets were predicted. Protein-protein interaction analysis identified 10 hub targets, including IL-6, TNF, EGFR, TP53, AKT, STAT3, SRC, CTNNB1, TLR4, and MMP-9. Enrichment analyses suggested that YQHX may exert its effects through modulation of lipid metabolism and inflammation. Molecular docking demonstrated strong binding affinities between the proteins EGFR, SRC, and AKT and their corresponding compounds. In ApoE ^⁻/⁻ mice fed a high-fat diet, YQHX significantly attenuated atherosclerotic plaque progression, improved lipid metabolism disorders, suppressed inflammatory responses, reduced macrophage infiltration in plaque areas, and inhibited the phosphorylation of key target proteins, including SRC and AKT, within atherosclerotic plaques. Conclusion This study provides novel insights by identifying potential active compounds and elucidating that YQHX may improve AS via the SRC/ AKT signaling pathway.