Xintongtai Granule: Investigating the serum pharmacology and mechanisms of action against atherosclerosis

•Conducting ex vivo chemical composition analysis of Xintongtai granule using UPLC-Q-TOF-MS/MS technology, we achieved high-resolution and high-sensitivity component detection. This has provided an advanced tool for in-depth research on traditional Chinese medicine formulations.•Successful attribution and analysis of the chemical composition of Xintongtai granule revealed their complex pharmacologically active components, laying the foundation for a deeper understanding of the mechanisms underlying traditional Chinese medicine in the treatment of atherosclerosis.•Through the study of medicated serum, the successful identification of the bloodstream components of Xintongtai Granule has been achieved, providing crucial clues for a deeper understanding of the metabolism and distribution of traditional Chinese medicine in the body.•Building upon the bloodstream components, a network pharmacology study was conducted, revealing the multi-level regulatory mechanisms of Xintongtai Granule on atherosclerosis. This provides profound theoretical support for the development of traditional Chinese medicine in the treatment of cardiovascular diseases. A serum medicinal chemistry analysis was performed to investigate the pharmacological basis of Xintongtai granule and to predict the potential mechanism of anti-atherosclerotic action based on the blood components. UPLC-Q-TOF-MS/MS was used to analyze the in vitro chemical composition and in vivo blood components of Xintongtai granule, and to detect the blood drug concentration. The PPI network was constructed by collecting blood components and disease targets through the network pharmacology method, and the key targets were subjected to GO and KEGG functional enrichment analyses, so as to construct the topology network of drug-component-target-disease, and to validate the network by molecular docking. The UPLC-Q-TOF-MS/MS analysis identified 69 chemical components in Xintongtai granule, including 19 prototype circulating components and 9 metabolites in the bloodstream. Network pharmacology analysis revealed 115 intersecting targets for the circulating components, from which 10 core targets were selected. GO and KEGG analyses unveiled associated signaling pathways and biological processes. The construction of a topology network and preliminary molecular docking provided insights into its mechanism of action. The mechanism underlying the anti- atherosclerosis effect of Xintongtai granule may be associated with the intervent