Liang Bixing, Wu Wenyu, He Fan, Yang Bing, Tang Dongxin
Guizhou University of Traditional Chinese Medicine, Guiyang, 550005, China.
The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine oncology department, No.50 Shidong Road, Nanming District, Guiyang, 550001, Guizhou, China.
Discov Oncol. 2025 Jun 6;16(1):1016. doi: 10.1007/s12672-025-02633-w.
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with limited therapeutic options and poor long-term survival. Hypericum japonicum Thunb. (Tianjihuang), a traditional Chinese medicine exhibits promising anticancer properties. This study aims to elucidate the multi-target mechanisms of Tianjihuang in treating HCC using network pharmacology and molecular docking techniques.
The active components of Tianjihuang and their targets were retrieved from TCMSP, PubChem, and Swiss Target Prediction databases. HCC-related targets were identified using GeneCard, OMIM, and TTD databases, and overlapping targets were analyzed. Protein-protein interaction (PPI) networks were constructed and analyzed using Cytoscape. Functional enrichment analysis of key targets was performed via GO and KEGG pathways. Kaplan-Meier curves assessed the clinical relevance of core targets, and molecular docking evaluated the binding affinities between Tianjihuang components and key targets.
Tianjihuang contained seven bioactive components targeting 207 genes, with 77 overlapping HCC-related targets. PPI analysis identified key targets, including AKT1, STAT3, EGFR, and ESR1, which play pivotal roles in HCC pathogenesis. GO and KEGG analysis revealed that Tianjihuang's anti-HCC effects involve multiple biological processes and pathways, such as cell proliferation, apoptosis, and PI3K-Akt signaling. Molecular docking results showed high binding affinities of key components, such as quercetin and gallic acid, with core targets supporting their potential therapeutic effects.
This study demonstrates that Tianjihuang exerts its anti-HCC effects through a multi-component, multi-target, and multi-pathway mechanism. These findings provide a scientific foundation for the clinical application of Tianjihuang and highlight its potential as a complementary therapy for HCC.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因，治疗选择有限且长期生存率低。地锦草，一种传统中药，具有有前景的抗癌特性。本研究旨在利用网络药理学和分子对接技术阐明地锦草治疗HCC的多靶点机制。
从中药系统药理学数据库与分析平台（TCMSP）、美国国立医学图书馆的化学物质数据库（PubChem）和瑞士靶点预测数据库中检索地锦草的活性成分及其靶点。使用基因卡片数据库（GeneCard）、在线人类孟德尔遗传数据库（OMIM）和治疗靶点数据库（TTD）鉴定HCC相关靶点，并分析重叠靶点。使用Cytoscape构建和分析蛋白质-蛋白质相互作用（PPI）网络。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）通路对关键靶点进行功能富集分析。Kaplan-Meier曲线评估核心靶点的临床相关性，分子对接评估地锦草成分与关键靶点之间的结合亲和力。
地锦草含有七种生物活性成分，靶向207个基因，其中77个与HCC相关的重叠靶点。PPI分析确定了关键靶点，包括AKT1、STAT3、表皮生长因子受体（EGFR）和雌激素受体1（ESR1），它们在HCC发病机制中起关键作用。GO和KEGG分析表明，地锦草的抗HCC作用涉及多个生物学过程和通路（如细胞增殖、凋亡和PI3K-Akt信号传导）。分子对接结果显示，关键成分（如槲皮素和没食子酸）与核心靶点具有高结合亲和力，支持它们的潜在治疗作用。
本研究表明，地锦草通过多成分、多靶点和多通路机制发挥其抗HCC作用。这些发现为地锦草的临床应用提供了科学依据，并突出了其作为HCC辅助治疗的潜力。
