基于网络药理学和分子对接法探讨黄芪治疗前列腺癌的机制

Exploring the Mechanism of Astragalus membranaceus in the Treatment of Prostate Cancer Based on Network Pharmacology and Molecular Docking

摘要: 运用网络药理学与分子对接探索黄芪治疗前列腺癌的作用机制。方法：通过借助中药系统药理学数据库及分析平台(TCMSP)筛选黄芪的成分及作用靶点，使用OMIM和GeneCards数据库筛选HT靶点；采用Cytoscape软件构建化学成分–潜在靶点网络图和蛋白相互作用网络图，进而筛选出关键靶点，借助DAVID数据库对靶点进行GO分析和KEGG通路分析；使用AutoDock Vina进行分子对接，初步筛选并进一步验证黄芪中的核心化学成分。结果：从黄芪中得到16个活性化合物及；筛选出与前列腺癌相关作用靶点172个；黄芪可以通过调节AGE-RAGE信号通路、PI3K-Akt信号通路、IL-17信号通路、MAPK信号通路、肿瘤坏死因子信号通路等对前列腺癌发挥治疗作用。其中CCND1、MYC、MAPK1、AKT1、ESR1、TNF、RELA、TP53、RB1、IL6、JUN、FOS、MAPK14等基因可能为关键靶点；分子对接结果显示：槲皮素与FOS蛋白的亲和力较好。结论：黄芪治疗前列腺癌的潜在作用机制具有多成分–多靶点–多通路的特点，为阐述黄芪治疗前列腺癌的作用机制和开展进一步研究提供依据。

Abstract: Objective: Using network pharmacology and molecular docking to explore the mechanism of Astragalus membranaceus in the treatment of prostate cancer. Methods: The components and action targets of Astragalus membranaceus were screened by the pharmacological database and analysis platform (TCMSP), and the HT targets were screened by OMIM and GeneCards database. Cytoscape software was used to construct the chemical components-potential target network and protein in-teraction network, and then the key targets were screened out. The GO analysis and KEGG pathway analysis of the targets were performed with the help of DAVID database. AutoDock Vina was used for molecular docking to preliminarily screen and further to verify the core chemical components in Astragalus membranaceus. Results: Sixteen active compounds were obtained from Astragalus membranaceus. 172 targets related to prostate cancer were screened out. Astragalus membranus can play a therapeutic role in prostate cancer by regulating AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, IL-17 signaling pathway, MAPK signaling pathway, tumor necrosis factor signal-ing pathway, etc. Among them, CCND1, MYC, MAPK1, Akt1, ESR1, TNF, RELA, TP53, RB1, IL6, Jun, FOS, MAPK14 and other genes may be key targets. The results of molecular docking showed that quercetin had a good affinity with FOS protein. Conclusion: The potential mechanism of Astragalus membranaceus in the treatment of prostate cancer has the characteristics of multi-component, mul-ti-target and multi-pathway, which provides the basis for further study on the mechanism of Astragalus membranaceus in the treatment of prostate cancer.