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基于网络药理学、分子对接和体外验证探索[药物名称]治疗肝癌的作用机制

Exploration of the Mechanism of Action of in the Treatment of Liver Cancer Based on Network Pharmacology, Molecular Docking and in vitro Validation.

作者信息

Zhan Shuimeng, Lu Xinyan, Guo Hongyan, Liu Yang, Li Zhi, Xu Wei, Xia Fang, Tang Huanjun, Tian Yi, Chen Jing, Lin Xuan

机构信息

Department of Endocrinology, CR & WISCO General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, People's Republic of China.

School of Medicine, Wuhan University of Science and Technology, Wuhan, Hubei, People's Republic of China.

出版信息

J Hepatocell Carcinoma. 2025 Aug 28;12:1973-1990. doi: 10.2147/JHC.S527095. eCollection 2025.

DOI:10.2147/JHC.S527095
PMID:40904605
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12402425/
Abstract

PURPOSE

The anti-tumor effects of , as a medicinal and dietary Chinese medicine, have long been documented. However, the mechanism of action for its therapeutic effect has not been fully elucidated.

METHODS

The chemical constituents of were screened using PubMed, CNKI, and Wanfang databases. Swiss Target Prediction was used to predict ingredient targets, while liver cancer targets were obtained from multiple databases. Venny 2.1.0 software identified intersection genes between the drug and disease, and a Protein-Protein Interaction (PPI) network was constructed. The DAVID database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Following this, the compound molecules were docked onto the core targets, and a visual analysis was conducted. The network pharmacology results were experimentally validated through in vitro studies with HepG2 cells.

RESULTS

The study identified 17 core components and 374 ingredient targets, with 1,249 disease targets collected from databases, yielding 50 overlapping targets. GO analysis revealed 284 Biological Process (BP) terms, 38 Cellular Component (CC) terms, and 75 Molecular Function (MF) terms. KEGG enrichment highlighted key pathways, including Pathways in cancer, PI3K-AKT signaling, Prostate cancer, and Proteoglycans in cancer. Molecular docking showed strong activity of Butin, Skimmin, and N-p-Coumaroyltyramine with core targets AKT1, EGFR, and CCND1. In vitro experiments demonstrated that aqueous extracts significantly inhibited HepG2 cell proliferation. Western blotting analysis further revealed that the extracts downregulated the expression levels of p-PI3K, PI3K, AKT1, EGFR, and CCND1 proteins.

CONCLUSION

The key active components of in treating liver cancer include butin, skimmin, and N-p-coumaroyltyramine, etc. The specific mechanism of action may be related to the modulation of targets such as p-PI3K/PI3K, AKT1, EGFR, and CCND1, and signaling pathways such as PI3K-Akt.

摘要

目的

作为一种药食同源的中药,其抗肿瘤作用早已被记载。然而,其治疗效果的作用机制尚未完全阐明。

方法

利用PubMed、CNKI和万方数据库筛选该中药的化学成分。使用瑞士靶点预测工具预测成分靶点,同时从多个数据库获取肝癌靶点。Venny 2.1.0软件确定药物与疾病之间的交集基因,并构建蛋白质-蛋白质相互作用(PPI)网络。利用DAVID数据库进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。在此之后,将化合物分子与核心靶点进行对接,并进行可视化分析。通过对HepG2细胞的体外研究对网络药理学结果进行实验验证。

结果

该研究确定了17种核心成分和374个成分靶点,从数据库收集了1249个疾病靶点,得到50个重叠靶点。GO分析显示有284个生物过程(BP)术语、38个细胞成分(CC)术语和75个分子功能(MF)术语。KEGG富集突出了关键通路,包括癌症通路、PI3K-AKT信号通路、前列腺癌和癌症中的蛋白聚糖。分子对接显示柯因、紫铆因和N-对香豆酰酪胺与核心靶点AKT1、表皮生长因子受体(EGFR)和细胞周期蛋白D1(CCND1)具有较强活性。体外实验表明该中药水提取物显著抑制HepG2细胞增殖。蛋白质印迹分析进一步显示提取物下调了p-PI3K、PI3K、AKT1、EGFR和CCND1蛋白的表达水平。

结论

该中药治疗肝癌的关键活性成分包括柯因、紫铆因和N-对香豆酰酪胺等。具体作用机制可能与调节p-PI3K/PI3K、AKT1、EGFR和CCND1等靶点以及PI3K-Akt等信号通路有关。

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