基于网络药理学的准噶尔乌头炮制品抗卵巢癌作用机制研究

Anti-ovarian cancer mechanism of processed products of Aconitum soongaricum Stapf. based on network pharmacology

目的运用网络药理学探讨准噶尔乌头炮制品抗卵巢癌的作用机制。方法根据准噶尔乌头与乌头属植物具有化学亲缘性的特点,利用中药系统药理学数据库和分析平台(TCMSP)、中药分子机制的生物信息学分析工具(BATMAN-TCM)等数据库并结合文献收集、筛选准噶尔乌头及其炮制品、乌头属植物有效活性成分。利用Swiss、GeneCards、基因表达数据库(GEO)等数据库预测药物和疾病的靶点。采用Draw Venn Diagram软件识别准噶尔乌头炮制品抗卵巢癌关键靶点,在Cytoscape 3.6.1软件中构建"疾病-药物-成分-靶点"网络。利用String数据库和Cytoscape 3.6.1软件构建关键靶点蛋白互作网络图;利用DAVID和R软件对关键靶点进行富集分析。结果得到准噶尔乌头炮制品抗卵巢癌的有效活性成分27个,关键靶点152个。准噶尔乌头碱、脱氧乌头碱、次乌头碱等可能是主要活性成分,其作用于PIK3CA、PIK3CB、PIK3CD、PIK3CG、表皮生长因子受体(EGFR)等靶点,参与癌症途径信号通路、PI3K-Akt信号通路、血管内皮生长因子(VEGF)信号通路、缺氧诱导因子-1(HIF-1)信号通路等多条信号通路,发挥抗卵巢癌作用。结论准噶尔乌头炮制品抗卵巢癌具有多成分、多靶点、多通路的特点,为开发具有民族特色的抗卵巢癌新药提供了思路。

Objective To explore the anti-ovarian cancer mechanism of processed products of Aconitum soongaricum Stapf. based on network pharmacology. Methods According to the characteristics of chemical phylogeny in Aconitum soongaricum Stapf. and Aconitum, the databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) in combination with literatures were used to collect and screen effective active ingredients of Aconitum soongaricum Stapf. and its processed products as well as Aconitum plants. Databases such as Swiss, GeneCards and Gene Expression Omnibus(GEO) were used to predict the targets of drugs and diseases. Draw Venn Diagram software was used to identify the key targets of processed products of Aconitum soongaricum Stapf. against ovarian cancer, and a "disease-drug-component-target" network was built in the Cytoscape 3.6.1 software. String database and Cytoscape 3.6.1 software were used to construct the key target protein interaction network diagram. DAVID and R software were used to perform enrichment analysis of key targets. Results A total of 27 effective active ingredients and 152 key targets of processed products of Aconitum soongaricum Stapf. against ovarian cancer were obtained.Songorine,deoxyaconitine and hypoaconitine might be the main active ingredients,which acted on PIK3 CA,PIK3 CB,PIK3 CD,PIK3 CG,epidermal growth factor receptor( EGFR) and other targets,and participated in cancer pathway signaling pathways,PI3 K-Akt signaling pathways,vascular endothelial growth factor( VEGF) signal pathways,hypoxia inducible factor-1( HIF-1) signaling pathways and other signaling pathways to play an anti-ovarian cancer effect. Conclusion Processed products of Aconitum soongaricum Stapf. against ovarian cancer have the characteristics of multiple components,multiple targets and multiple pathways,which can provide ideas for the development of new anti-ovarian cancer drugs with national characteristics.