基于网络药理学和分子对接技术研究蒲公英治疗乳腺增生的潜在机制

Study on the potential mechanism of Pu Gong Ying in treating breast hyperplasia based on network pharmacology and molecular docking

本研究应用网络药理学方法研究蒲公英治疗乳腺增生的作用靶点及作用路径,结合分子对接技术分析蒲公英中活性成分和关键靶点之间的亲和性。网络药理学结果发现蒲公英中的15个活性成分涉及的261个作用靶点与乳腺增生疾病关联的2455个作用靶点共有交集靶点90个(在蛋白质交互网络中包含89个相关靶点和1个无关靶点)。Cytoscope软件中cytoHubba插件获得的度值前10靶点与MOCDE插件获得的评分前10的靶点交集获得的CASP3、EGFR、ESR、ERBB2、MMP9和PTGS2靶点作为核心靶点。富集分析确定了284个具有统计学意义的基因本体论术语。京都基因与基因组百科全书分析了125条具有统计学意义通路,主要参与调控癌症通路、PI3K-Akt信号通路、MAPK信号通路、癌症中的小分子RNAs和化学致癌受体激活等。分子对接结果显示木犀草素、芹菜素和异鼠李素与核心靶点有很好的结合活性。蒲公英能够通过多路径、多靶点治疗乳腺增生,阐明了潜在作用机制,并为乳腺增生靶向治疗和乳腺癌预防提供重要启示。

In the present study, network pharmacology was employed to elucidate the targets and pathways involved in the treatment of breast hyperplasia(BH) by Pu Gong Ying(PGY). Molecular docking was utilized to analyze the interaction between PGY and key targets based on the findings of network pharmacology. The intersection of 261 targets associated with 15 PGY compounds and 2455 targets related to BH yielded 90 common targets(89 of which were included in the protein-protein interaction(PPI) network, while one target did not exhibit interactions with any other targets in the PPI network). The top 10 hub targets ranked in the PPI network and the top 10 targets according to the Molecular Complex Detection(MOCDE) score were intersected, resulting in the identification of CASP3, EGFR, ESR1, ERBB2, MMP9, and PTGS2 as key targets, as determined by different algorithms. Gene Ontology(GO) functional enrichment analysis revealed 284 biological components. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis identified 125 pathways, primarily associated with the regulation of pathways in cancer, the PI3K-Akt signaling pathway, the MAPK signaling pathway, microRNAs in cancer, chemical carcinogenesis-receptor activation, and others. Molecular docking results demonstrated the favorable binding efficacy of PGY9, PGY10, and PGY11 with the core targets. The findings suggested that PGY exerted its therapeutic effects on BH through multiple targets and biological pathways. This study contributed to the understanding of the molecular mechanisms underlying BH development and provided implications for BH-targeted therapy and even breast cancer prevention.