广西医学

目的基于网络药理学与分子对接技术探讨人参皂苷Rh2抗肝细胞癌的作用机制。方法在中药系统药理学数据库与分析平台、PharmMapper等数据库获取人参皂苷Rh2的作用靶点，在GeneCards®、OMIM®数据库中检索肝细胞癌相关靶点，通过Venny在线工具获取两者交集靶点。利用STRING数据库构建交集靶点，蛋白⁃蛋白相互作用（PPI）网络，并进行拓扑学分析筛选核心靶点，通过DAVID数据库进行交集靶点富集分析。采用AutoDockTools、PyMOL软件将人参皂苷Rh2与核心靶点进行分子对接。结果共筛选获得人参皂苷Rh2作用靶点252个，肝细胞癌相关靶点1 566个，两者的交集靶点共91个。核心靶点包括Caspase⁃3（CASP3）、肿瘤坏死因子（TNF）、前列腺素内过氧化物合酶2（PTGS2）、信号转导和转录激活因子3、表皮生长因子受体、白蛋白。富集分析结果显示，交集靶点主要富集于细胞质基质、细胞核、细胞质等细胞组分，主要涉及蛋白质结合、腺嘌呤核苷三磷酸结合、蛋白激酶活性等分子功能，以及细胞信号转导、磷酸化等生物过程，与癌症通路、丝裂原活化蛋白激酶（MAPK）信号通路、磷脂酰肌醇3激酶⁃蛋白激酶B（PI3K⁃AKT）信号通路等信号通路密切相关。分子对接结果显示，人参皂苷Rh2与CASP3、TNF、PTGS2之间的结合能均≤-7 kcal/mol。结论人参皂苷Rh2可能通过调控CASP3、TNF、PTGS2等靶点，干预癌症通路、MAPK信号通路、PI3K⁃AKT信号通路等信号通路发挥抗肝细胞癌作用。

Objective To explore the mechanism of ginsenoside Rh2 against hepatocellular carcinoma (HCC) based on network pharmacology and molecular docking technique. Methods Effect targets of ginsenoside Rh2 were retrieved from the databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and PharmMapper. HCC⁃related targets were searched in the GeneCards® and OMIM® databases. Intersection targets were obtained using the Venny online tool. Based on these intersection targets, a protein⁃protein interaction (PPI) network was constructed using the STRING database, and core targets were screened through topological analysis. Enrichment analysis of intersection targets was performed using the DAVID database. Molecular docking between ginsenoside Rh2 and the core targets was conducted using AutoDockTools and PyMOL software. Results A total of 252 effect targets for ginsenoside Rh2 and 1566 targets related to HCC were screened, resulting in 91 intersection targets. Core targets included Caspase⁃3 (CASP3), tumor necrosis factor (TNF), prostaglandin⁃endoperoxide synthase 2 (PTGS2), signal transducer and activator of transcription 3, epidermal growth factor receptor, and albumin. Enrichment analysis results revealed that the intersection targets were enriched in cellular components such as cytosol, nucleus, and cytoplasm. They were primarily involved in molecular functions including protein binding, adenosine triphosphate binding, and protein kinase activity, as well as biological processes such as cell signal transduction and phosphorylation. These targets were closely associated with pathways including pathways in cancer, mitogen⁃activated protein kinase (MAPK) signaling pathway, and phosphatidylinositol 3⁃kinase/protein kinase B (PI3K⁃AKT) signaling pathway. Molecular docking results indicated that the binding energies between ginsenoside Rh2 and CASP3, TNF, and PTGS2 were all ≤-7 kcal/mol. Conclusion Ginsenoside Rh2 may exert anti⁃HCC effects by regulating targets such as CASP3, TNF, and PTGS2, thereby intervening in pathways including pathways in cancer, MAPK signaling pathway, and PI3K⁃AKT signaling pathway.