Exploration of the mechanism of Tongmai Jiangzhuo Decoction in treating atherosclerosis based on network pharmacology and experimental validation.

OBJECTIVES

Atherosclerosis (AS) is a dyslipidemia-driven immunoinflammatory disease. While Tongmai Jiangzhuo Decoction (TMJZ) clinically improves cardiovascular outcomes through lipid-lowering effects, its molecular mechanisms against AS remain unelucidated. This study aimed to systematically investigate the anti-atherogenic mechanisms of TMJZ.

METHODS

Main active components of TMJZ and their targets were identified using Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Potential therapeutic targets were sourced from Online Mendelian Inheritance in Man (OMIM) and GeneCards. Protein-protein interactions (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted using Cytoscape. Molecular docking was performed with AutoDockTools, AutoDock Vina, and PyMOL. Apolipoprotein E (ApoE)-deficient mice were used to validate the targets.

RESULTS

A total of 395 predicted intersection target genes between TMJZ targets and atherogenic-related targets were identified. Key anti-atherosclerosis targets of TMJZ included Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), Cluster of Differentiation 36 (CD36, fatty acid translocase), Interleukin 6 (IL6), Insulin (INS), AKT Serine/Threonine Kinase 1 (AKT1), Tumor Necrosis Factor (TNF), Tumor Protein p53 (TP53), Interleukin 1 Beta (IL1B), Catenin Beta 1 (CTNNB1), and Apolipoprotein E (APOE). Among these, PPARγ/CD36 signaling emerged as a pivotal pathway. In vivo studies demonstrated that TMJZ improved blood lipids, reduced plaque area and lipid deposition, upregulated PPARγ expression, and downregulated CD36 expression in aortic tissues. Additionally, TMJZ upregulated Liver X Receptor Alpha (LXRα) and ATP Binding Cassette Subfamily A Member 1 (ABCA1), promoting reverse cholesterol transport.

CONCLUSIONS

TMJZ alleviates atherosclerosis by inhibiting lipid uptake via the PPARγ/CD36 pathway.