基于网络药理学和分子对接研究艾叶治疗原发性痛经的分子机制

Research on the Molecular Mechanism of Folium Artemisiae Argyi in Treating Primary Dysmenorrhea Based on Network Pharmacology and Molecular Docking

目的:采用网络药理学研究艾叶干预原发性痛经的潜在靶点和机制。方法:通过中药系统药理数据库及分析平台(TCMSP)筛选有效化合物,经美国国立卫生研究院(NIH)的开放化学数据库(PubChem)和预测分子亲脂性和水溶性程序ALOGPS 2.1确定,并预测艾叶作用靶点;通过DisGeNET、NCBI-Gene、DrugBank和GeneCards数据库收集原发性痛经靶点。通过功能性蛋白关联网络(String)和可视化网络软件(Cytoscaoe3.6)筛选出交集基因中的核心基因以及确定信号通路。结果:通过分子式预测艾叶的化合物作用靶点有442个。此外,4个数据库共收集到351个靶点,这两个靶点集相交集的靶点有66个。通过软件Cytoscape3.6筛选出丝氨酸/苏氨酸激酶(AKT1)、前列腺素-内过氧化物合酶(PTGS2)、血管内皮生长因子(VEGFA)等5个靶标蛋白核心基因,并构建药物-化合物-靶点-疾病网络图。在String数据库中显示艾叶与原发性痛经之间的信号通路有114条,最显著的通路集中在亚油酸代谢(hsa00591)、花生四烯酸代谢(hsa00590)、甾体激素生物合成(hsa00140)和卵巢甾体生成(hsa04913)信号通路。使用分子对接软件Autodock对5个核心靶点与9个化合物之间做分子对接,发现9个化合物中有8个化合物能和5个核心靶点有良好的对接。最后通过三维分子软件PyMOL计算靶点-化合物之间的作用关系。结论:该研究通过网络数据库及计算机分析验证初步发现艾叶干预原发性痛经的活性成分,为进一步深入验证和药物开发提供理论依据。

Objective:To study the potential targets and mechanisms of Folium Artemisiae Argyi intervention with primary dysmenorrhea through network pharmacology.Methods:The effective compounds were screened by TCMSP,and the molecular formulas of the compounds were determined by PubChem and ALOGPS 2.1,and the targets of Folium Artemisiae Argyi were predicted;the target points of primary dysmenorrhea were collected through the four databases of DisGeNET,NCBI-Gene,DrugBank and GeneCards.By String and Cytoscape3.6,the intersection genes were screened for core genes,and signal pathways were determined.Results:According to the molecular formula,there were 442 targets for the compounds of Folium Artemisiae Argyi.In addition,a total of 351 targets were collected by four databases,and 66 targets were intersected by the two target sets.Fifteen core genes such as AKT1,PTGS2 and VEGFA were screened out through the mode function of the software Cytoscape 3.6,and a drug-compound-target-disease network map was constructed.The String database showed that there were 114 signal pathways between Folium Artemisiae Argyi and primary dysmenorrhea.The most significant four pathways were linoleic acid metabolism(hsa00591),arachidonic acid metabolism(hsa00590),steroid hormone biosynthesis(hsa00140)and ovarian steroid production(hsa04913).Autodock was used to make molecular docking between the 5 core targets and 9 compounds,and it was found that 8 of the 9 compounds could dock well with the 5 core targets.Finally,PyMOL was used to calculate the relationship between the targets and the compounds.Conclusion:The study initially finds the active ingredients of Folium Artemisiae Argyi to interfere with primary dysmenorrhea through network database and computer analysis and verification,and provides theoretical basis for further in-depth verification and drug development.