The Mechanism of Buqi Jianzhong Decoction in Treating Hepatocellular Carcinoma via AI-assisted Network Pharmacology and Experimentation

Introduction: Hepatocellular carcinoma (HCC) is one of the deadliest cancers. Traditional Chinese medicine has been used as an adjuvant therapy for HCC. Buqi Jianzhong Decoction (BJD), a classic liver-soothing formula with an undefined mechanism, was studied via multi-databases and Artificial Intelligence (AI) to complete key drug development steps. Methods: First, potential active ingredients and target genes were screened using the TCMSP database, and gene expression data from the GEO database were combined with AI algorithms to construct a disease-related gene network. Then, through AI-assisted screening with the Chembl database, candidate compounds highly correlated with core targets were identified. Next, molecular docking and molecular dynamics simulation techniques were used to assess the binding performance. Finally, experiments were conducted to validate the efficacy and safety of the candidate complexes. Results: The study found 17 potential core targets through protein-protein interaction network and GEO dataset analysis. Finally, the core targets were obtained based on a multi-algorithm approach. KEGG analysis indicated that BJD may inhibit HCC by targeting pathways. The AIbased ChEMBL database screening based on core targets identified 82 highly active compounds, and the top 20 compounds of pIC50 were selected for molecular docking with the core targets. Finally, it was verified that BJD could inhibit the proliferation, cloning, and migration of hepatocellular carcinoma cells, while reducing the p-PI3K, p-AKT, and β-catenin expression. Discussion: BJD exerts therapeutic effects on HCC through multi-components, multi-targets, and multi-pathways, providing a theoretical basis for experimental studies. Conclusion: The results aided the modernization of TCM and the development of multitargeted cancer drugs.