TITLE:
The Network Pharmacology and Multi-Omics Study on the Anti-Hepatocellular Carcinoma Effects of Zhuang Medicine Compound Tiecao Capsules
AUTHORS:
Shuhan Wang, Yongle Li, Zhenzhen Ren, Xiaomei Xie, Rong He, Lihe Jiang
KEYWORDS:
Liver Cancer, Zhuang Medicine Compound Tiecao Capsule, Network Pharmacology, Bioinformatics
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.11,
November
10,
2025
ABSTRACT: Objective: To elucidate the mechanism of the Zhuang medicine compound Tiecao Capsule against Hepato-Cellular Carcinoma (HCC) using network pharmacology. Methods: Active ingredients and their targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) Database and literature. Disease-drug common targets were screened using GeneCards. A PPI network was constructed using STRING, and the top 30 key targets were screened using R software. Human Protein Atlas (HPA) was used to explore the protein expression levels of core targets, and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) was used to analyze correlations among the targets. Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Eighteen metabolites related to liver cancer were selected from Human Metabolome Database (HMDB), and HCC-related metabolic pathways were analyzed using the metabolomics analysis platform MetaboAnalyst. Molecular docking was validated using AutoDock. Prognostic validation was performed using The Cancer Genome Atlas (TCGA) clinical data combined with Grammar of Graphics Plot 2(GGPLOT2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Single-cell sequencing was used to locate target expression. Results: 113 intersecting genes and 6 core targets (AKT1, VEGFA, IL6, MAPK8, EGFR, SRC) were obtained. Significant correlations were found between IL6-AKT1, MAPK8-SRC, and VEGFA-EGFR; MAPK8, SRC, and VEGFA proteins were highly expressed and correlated with TNM stage and Grade, with low expression associated with better survival; bile acid and D-arginine metabolism were abnormal; SRC/VEGFA were mainly enriched in macrophages and fibroblasts. Conclusion: Zhuang medicine compound Tiecao Capsule may potentially inhibit the progression of hepatocellular carcinoma by targeting multiple proteins such as AKT1/VEGFA/SRC through active ingredients including quercetin and kaempferol. This proposed mechanism involves the regulation of the tumor microenvironment at both protein and metabolomic levels, and the modulation of pathways such as PI3K-AKT signaling and tumor microenvironment metabolism.