Unraveling the mechanism of core prescription in primary liver cancer: integrative analysis through data mining, network pharmacology, and molecular simulation.

This study aims to identify core Traditional Chinese Medicine compound prescriptions (TCM CPs) for Primary Liver Cancer (PLC) and their underlying mechanisms. A comprehensive search was conducted using China National Knowledge Infrastructure (CNKI) and the Chinese Medical Code V5.0, identifying 151 TCM CPs. Medication frequency and association rules were analyzed with TCMICS V3.0, while active compounds were identified via TCMSP and TCMIP V2.0. Targets were predicted using Swiss Target Prediction, and disease targets from DisGeNET, OMIM, and GeneCards were cross-referenced. A protein-protein interaction (PPI) network was constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using DAVID. In the process of studying active compounds, an orthogonal experiment was carried out on the extraction process of relevant herbs. The results of the orthogonal experiment and range analysis showed that for the extraction rate of the extract and the content of paeoniflorin, the decoction cycles had the most significant impact, followed by soaking time and water volume. The optimal extraction conditions were determined as soaking time of 30 min, water volume of tenfold, and 3 decoction cycles. Under these conditions, the extract yield reached 42.49%, and the paeoniflorin content was 73.60 mg/25.02 g crude herb (equivalent to 2.94 mg/g). ANOVA analysis further confirmed the significance of these factors. The results revealed 109 common targets between TCM component targets and disease targets, with key targets including STAT3, SRC, AKT1, HRAS, and PIK3CA. Molecular docking showed strong binding affinities of paeoniflorin and 3,5,6,7-tetramethoxy-2-(3,4,5-trimethoxyphenyl) chromone to PLC targets, with ADME predictions favoring paeoniflorin. Furthermore, Molecular Dynamics (MD) simulations revealed that paeoniflorin maintains stable binding to the target proteins, demonstrating promising conformational stability. The CCK-8 assay demonstrated that the core TCM CP exerted a dose-dependent inhibitory effect on HepG2 cells. After 24 h of intervention, the IC Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-025-00352-2.