TITLE:
Exploring the Molecular Mechanisms of Yinqiao Shihu Decoction in the Treatment of Hepatocellular Carcinoma Based on Network Pharmacology, Molecular Docking, and Single-Cell Sequencing Analysis
AUTHORS:
Yazhou Yang, Yongle Li, Xuanhua Chen, Xinling Shang, Jun Tang, Lihe Jiang
KEYWORDS:
Yinqiao Shihu Decoction, Hepatocellular Carcinoma, Network Pharmacology, Key Targets
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.13 No.12,
December
16,
2025
ABSTRACT: Objective: To explore the potential molecular mechanisms of Yinqiao Shihu Decoction (YSD) in the treatment of Hepatocellular Carcinoma (HCC) using a network pharmacology-based approach. Methods: The chemical constituents of each herb in YSD were retrieved from the TCMSP and TCMID databases, and the active compounds and their corresponding targets were identified. Differentially expressed genes were obtained from the GEO and TCGA databases, while key disease-related targets were screened using the TTD, OMIM, and GeneCards databases. Protein-protein interaction networks were constructed, followed by Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Molecular docking between core active components and hub target proteins was performed using AutoDock software. The correlation between the expression of core genes and overall survival in HCC patients was analyzed via the GEPIA2 online platform. Single-cell transcriptomic data (GSE290925) were analyzed using Seurat to explore the cellular distribution of hub genes. Results: A total of 161 active compounds and 101 key therapeutic targets of YSD for HCC were identified. ALB, IL6, CASP3, EGFR, and VEGFA were recognized as key hub proteins. Enrichment analysis indicated significant involvement in transcriptional regulation, apoptosis, and PI3K-Akt and MAPK signaling pathways. Quercetin, kaempferol, luteolin, wogonin, and β-sitosterol were identified as major active components, showing strong binding affinities with RAF1, PTGS1, and NCOA2. PTGS1 and RELA expression were negatively correlated with overall survival in HCC patients. Single-cell analysis revealed that NCOA2, RELA, and RAF1 were highly expressed in monocytes, PTGS1 in NK cells, and CCND1 in fibroblasts, highlighting their potential roles in the HCC microenvironment. Conclusion: YSD may treat HCC through a multi-component and multi-target mechanism. Core compounds such as quercetin, kaempferol, luteolin, wogonin, and β-sitosterol act on key targets including ALB, IL6, CASP3, VEGFA, and RAF1 via PI3K-Akt and MAPK pathways. Single-cell analysis indicated cell-type-specific expression of hub genes, suggesting that YSD may regulate tumor immunity and microenvironment. These findings provide a theoretical basis for YSD’s clinical application in HCC.