Qigui jiangzhi formula ameliorates atherosclerosis by inhibiting macrophage foam cell formation via the PI3K/AKT/ABCA1 pathway

OBJECTIVE: Qigui Jiangzhi Formula (QGJZF) is a traditional Chinese medicine formulation developed based on the principles of regulating Qi, warming Yang, and resolving dampness. All of its herbs have historically been used to treat obesity, hypertension, and hyperlipidemia. However, its therapeutic mechanism in atherosclerosis (AS)-related cardiovascular disease remains unclear. This study aimed to investigate the anti-atherosclerotic activity and explain the mechanism of QGJZF. METHODS: PCSK9 overexpressing mice induced by high-fat diet were used to establish an in vivo model. Aortic pathology and inflammation were assessed via histology, immunofluorescence, and Enzyme-linked immunosorbent assay. Chemical characterisation was performed by LC-MS. Network pharmacology and multi-omics were combined to elucidate the mechanism of QGJZF, validated by molecular docking and surface plasmon resonance (SPR). An in vitro foam cell model using ox-LDL-induced RAW264.7 macrophages was analysed by qPCR and Western blot. RESULTS: QGJZF effectively reduced aortic lipid plaque deposition, ameliorated plaque pathology, and suppressed macrophage infiltration in AS mice. LC-MS identified 93 non-volatile components, including 16 blood-entering constituents and 23 metabolites. Network pharmacology and multi-omics analyses indicated QGJZF regulates lipid metabolism via the PI3K-AKT pathway. Molecular docking and SPR confirmed strong binding of five major blood-entering components to PI3K/AKT proteins. In vitro, QGJZF activates the PI3K-AKT pathway, upregulated ABCA1 expression, inhibited macrophage foam cell formation, and improved lipid metabolism. CONCLUSION: QGJZF inhibits the formation of foam macrophages through the PI3K-AKT-ABCA1 signalling pathway, thereby improving AS. This provides a scientific foundation for the clinical application of QGJZF in AS-related cardiovascular disease.