Study on the Active Constituents and Molecular Mechanism of Zhishi Xiebai Guizhi Decoction in the Treatment of CHD Based on UPLC-UESI-Q Exactive Focus, Gene Expression Profiling, Network Pharmacology, and Experimental Validation

[Image: see text] As one of the most common clinical cardiovascular diseases (CVDs), coronary heart disease (CHD) is the most common cause of death in the world. It has been confirmed that Zhishi Xiebai Guizhi decoction (ZXGD), a classical prescription of the traditional Chinese medicine (TCM), has achieved certain effects in the treatment of CHD; however, the mechanism still remains controversial. In this paper, an integrated approach, including UPLC-UESI-Q Exactive Focus, gene expression profiling, network pharmacology, and experimental validation, was introduced to systematically investigate the mechanism of ZXGD in the treatment of CHD. First, UPLC-UESI-Q Exactive Focus was applied to identify the chemical compounds of ZXGD. Then, the targets of the components for ZXGD were predicted by MedChem Studio software embed in the integrative pharmacology-based research platform of TCM, and the differentially expressed genes (DEGs) of CHD were obtained by gene expression profiling in gene expression omnibus database. The common genes of the above two genes were obtained by Venn analysis as the targets of GXGD in treatment with CHD. Third, the core targets were screened out by protein–protein interaction network analysis, and the kyoto encyclopedia of genes and genomes pathway enrichment analysis was performed by the database for annotation, visualization, and integrated discovery bioinformatics resources. After that, the formula–herb–compound–target–pathway network was constructed to explore the mechanism of ZXGD in the treatment of CHD. Finally, molecular docking and the vitro experiment were carried out to validate some key targets. As a result, a total of 39 compounds, 12 core targets, and 4 pathways contributed to ZXGD for the treatment of CHD. This study preliminarily provided a foundation for the study on the mechanism against CHD for ZXGD and may be a reference for the compatibility mechanism and the extended application of TCM compound prescription.