Integrating Network Pharmacology and Clinical Observation to Elucidate the Therapeutic Mechanisms of Yangzheng Xiaoji Decoction in Primary Liver Cancer.

Background: Primary liver cancer (PLC) is a leading cause of global cancer mortality. Yangzheng Xiaoji Decoction (YZXJD), a traditional Chinese medicine based on "Fuzheng Xiaoji" principles, is used as adjunctive PLC therapy, yet its underlying molecular mechanisms require further characterization. Methods: Active compounds from 13 herbs were retrieved via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database (OB ≥ 30%, DL ≥ 0.18). After identifying drug-disease target intersections, a compound-target-disease network was constructed using Cytoscape. PPI, GO, and KEGG analyses were performed. Concurrently, 40 patients with PLC were assigned, in a non-randomized prospective controlled design, to conventional therapy (control, n=20) or conventional therapy plus YZXJD (observation, n=20) for 4 weeks. Biochemical markers (AFP, AST, ALT, ALB, PT) and TCM syndrome scores were evaluated. Results: Network pharmacology identified 195 active compounds and 135 potential therapeutic targets. PPI screening revealed 25 core targets, with GRM5, TRPA1, ADRA1D, GRIA2, and NPY2R showing the highest connectivity. GO analysis yielded 215 enriched terms, while KEGG analysis highlighted 14 pathways, notably neuroactive ligand-receptor interaction and cGMP-PKG signaling. Clinically, both groups showed within-group reductions in AST, ALT, and AFP, but under a Bonferroni-adjusted threshold (P < 0.01) the between-group advantage for the observation group was most clearly evident for prothrombin time (PT), which improved in the observation group while it worsened in the control group. TCM syndrome scores decreased significantly in the observation group (P < 0.001) but worsened in the control group (P = 0.004). The total effective rate was 80.0% in the observation group versus 65.0% in controls (P = 0.048). Conclusion: Network pharmacology suggests that YZXJD may act against PLC through multi-component, multi-pathway mechanisms. In this preliminary, non-randomized observation, the addition of YZXJD was associated with improvements in hepatic function markers, serum AFP, and symptom burden. These findings are hypothesis-generating; the computational predictions and clinical signals require confirmation in adequately powered, randomized, and experimentally validated studies before YZXJD can be recommended for routine integration into PLC management.