The chemical composition analysis of Yixin Tongmai Granules using UHPLC-MS/MS and exploration of its potential mechanism in treatment of coronary artery disease based on network pharmacology and molecular docking

Yixin Tongmai Granules (YTG) is a popular Chinese herbal granules for the treatment of coronary artery disease (CAD), but its molecular pharmacological mechanism is still unclear. This article explores the mechanism of CAD treatment from the perspective of network pharmacology. We analyzed the chemical composition of YTG using UHPLC-MS/MS and identified 131 ingredients. The relative drug content of 33 ingredients exceeded 0.5%. These ingredients were further screened using the SwissADME platform with ADME criteria. Using the HIT database and SwissTargetPrediction platform, high probability targets for these ingredients were generated. Using Venn Diagram, 96 effective targets associated with CAD were identified, involving 14 core ingredients. This study imported these effective targets into the STRING platform and obtained the core targets through network topology analysis: TP53, STAT3, transcription factor Jun, MAPK3, MAPK1, AKT1, SRC, MYC, BCL2, transcription factor p65, TNF, and ESR2. Then enrichment analysis with Metascape platform indicated that, in the system network of YTG in anti-CAD, the principal pathways are "Lipid and Atherosclerosis", "Pathways in cancer", and "AGE-RAGE signaling pathway in diabetic complications." Next, the affinities between the core ingredients and their associated core targets were examined individually through molecular docking. Finally, based on deep mining of PubMed literature, this study investigated the relationship between each core target and CAD, the relationship between each core target and its associated core ingredients, and inferred the main pharmacological ingredients of YTG, namely Tanshinone IIA, Cryptotanshinone, Caffeic acid, Denshensu, Ononin, and Formononetin.