基于网络药理学和分子对接探讨冬虫夏草抗肿瘤的作用机制

目的 基于网络药理学方法和分子对接技术探究冬虫夏草抗肿瘤的作用机制。方法 利用TCMSP、CNKI、PubMed、Drugbank、Stitch和Swiss target prediction等平台检索冬虫夏草的化学成分和作用靶点;通过GeneCards、OMIM等数据库筛选肿瘤相关基因,运用Cytoscape 3.7.2构建冬虫夏草活性成分-靶点网络,通过String数据库对关键靶点构建网络互作(PPI)网络,并进行基因本体(GO)基因和京都基因和基因组百科全书(KEGG)通路富集分析,最后利用AutoDock Vina软件和Pymol软件对药物有效活性成分和关键靶点进行分子对接验证。结果 共得到冬虫夏草22个化合物,86个抗肿瘤共同靶点,主要包括环加氧酶(PTGS)2、丝裂原活化蛋白激酶3(MAPK3)、过氧化物酶体增生激活受体γ(PPARG)、胱天蛋白酶3(CASP3)、JUN基因等关键靶点。GO分析与KEGG通路结果显示,冬虫夏草抗肿瘤涉及到多种生物学过程以及PPAR、花生四烯代谢、5-羟色胺信号通路等多种信号通路。将关键化合物和靶点进行分子对接,提示冬虫夏草抗肿瘤可能的前5个主要活性成分11,14-二十碳二烯酸、花生四烯酸、黄豆黄素、胆甾醇和豆甾醇与关键靶点PTGS2、PTGS1、PGR、HMGCR和CNR1均能自发结合。结论 初步探讨了冬虫夏草抗肿瘤的主要活性成分、相关靶点及相关通路,发现冬虫夏草可以通过多成分、多靶点、多通路抗肿瘤,为后期实验验证提供了参考依据。

Antitumor mechanism of Cordyceps sinensis based on network pharmacology and molecular docking

Objective To investigate the anti-tumor mechanism of Cordyceps sinensis based on network pharmacological methods and molecular docking. Methods The chemical composition and action targets of Cordyceps sinensis were retrieved by TCMSP, CNKI, PubMed, Drugbank, Stitch, and Swiss target prediction platforms, tumor-related genes were screened by GeneCards, OMIM and other databases, Cytoscape 3.7.2 was used to construct Cordyceps sinensis active ingredient and target network, and PPI network was constructed from String database for key targets. GO function and KEGG pathway enrichment analysis were carried out, and finally AutoDock Vina software and Pymol software were used to verify the molecular docking of the active ingredients and key targets of the drug. Results A total of 22 compounds and 86 anti-tumor common targets of Cordyceps sinensis were obtained through screening, including key targets such as PTGS2, MAPK3, PPARG, CASP3, and JUN. GO analysis and KEGG pathway results showed that Cordyceps sinensis anti-tumor involves a variety of biological processes as well as a variety of signaling pathways such as PPAR, arachidonic metabolism, serotonin signaling pathway. The key compounds and the target were docking, suggesting that the top five possible anti-tumor components, 11, 14-eicosadienoic acid, arachidonic acid, soybean flavin, cholesterol, and stigmasterol, could spontaneously bind to the key targets, PTGS2, PTGS1, PGR, HMGCR and CNR1. Conclusion In this paper, the main active ingredients, related targets and related pathways of Cordyceps sinensis anti-tumor are preliminarily discussed, and it is found that Cordyceps sinensis can resist tumors through multi-component, multi-target and multi-pathway, which provides a reference basis for later experimental verification.