Mechanistic Investigation of Cyclovirobuxine D in Hepatocellular Carcinoma Treatment Through Network Pharmacology, Molecular Docking Simulations, and ADMET Prediction Analyses

The present study investigated the mechanism of cyclovirobuxine D in the treatment of liver neoplasms through network pharmacology and ADMET prediction. Potential targets of cyclovirobuxine D (CVB‐D) and hepatocellular carcinoma (HCC)‐related targets were retrieved from databases. The PPI network was constructed to screen core targets. GO and KEGG pathway enrichment analyses were performed. Molecular docking and molecular dynamics simulations were conducted for validation. Comprehensive ADMET prediction analyses(absorption, distribution, metabolism, excretion, and toxicity) profiling was conducted. PPI analysis revealed 10 core targets (AR, CDK2, NFKB1, MTOR, ESR1, etc.). Enrichment analyses demonstrated CVB‐D's potential therapeutic mechanisms through the hypoxia‐inducible factor‐1 (HIF‐1) signaling pathway. Molecular docking confirmed strong binding affinity between CVB‐D and core targets, while molecular dynamics simulations demonstrated conformational stability with the targets. ADMET studies demonstrated favorable safety profiles of this bioactive compound. It is hypothesized that CVB‐D may treat HCC by targeting MTOR, thereby inhibiting the PI3K/AKT/MTOR signaling pathway in HIF‐1. In addition, it is predicted that the expression of autophagy‐related factors will be influenced, thus playing a significant role in the treatment of HCC. ADMET profiling supported CVB‐D's pharmacological safety and therapeutic potential. This study provides new insights for research on CVB‐D in treating HCC.