Abstract
Purpose:
Hepatocellular carcinoma (HCC) poses a significant global health burden with limited therapeutic options. Traditional Chinese medicine (TCM), particularly Yangyin Fuzheng Jiedu Prescription (YFJP), has shown promise in improving patient outcomes, but its mechanisms are poorly understood. This study aimed to elucidate the key components and mechanisms of YFJP in treating HCC using an integrative approach combining network pharmacology, molecular docking, and experimental validation.
Patients and methods:
We analyzed data from 1021 HCC patients (481 treated with YFJP and 540 with Western medicine alone) using propensity score matching to minimize bias. Network pharmacology identified key components and targets of YFJP, with a focus on Jiedu Prescription (JDP). Molecular docking and dynamics simulations validated the binding affinity between core components and targets. GO and KEGG analyses elucidated biological functions and pathways. In vivo experiments using a tumor-bearing mouse model further validated the mechanisms.
Results:
YFJP significantly improved overall survival (P < .0001) and increased CD4+T and CD8+T cell counts (P < .05) in HCC patients compared to the control group. Network pharmacology analysis identified JDP as the core component of YFJP, with quercetin, luteolin, and apigenin as the key active compounds. GO and KEGG pathway analyses revealed that JDP modulates HCC through the regulation of cell death, immune response, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that JDP increases the proportion of CD8+T cells in the tumor microenvironment and inhibits apoptosis by downregulating the IL-6/STAT3 pathway. Molecular docking and dynamics simulations further confirmed the strong binding affinity of JDP's key compounds to STAT3, supporting their role in modulating this pathway.
Conclusion:
YFJP, particularly its core component JDP, enhances anti-tumor immunity and improves survival in HCC patients by modulating the IL-6/STAT3 pathway. These findings highlight YFJP as a promising adjuvant therapy for HCC, offering a multi-target approach to enhance anti-tumor immunity.