基于网络药理学和分子对接技术探讨黄芩-白术治疗先兆流产的机制

Discussion on Mechanism and Active Components of Scutellariae Radix-Atractylodis Macrocephalae Rhizoma in the Treatment of Threatened Abortion Based on Network Pharmacology and Molecular Docking

目的基于网络药理学和分子对接技术探讨黄芩-白术治疗先兆流产的潜在机制。方法利用TCMSP数据库筛选黄芩-白术的有效成分,并预测潜在靶基因,从GeneCards、NCBI、OMIM、DrugBank、DisGeNET数据库获取与先兆流产相关的靶基因,将两者取交集得到黄芩-白术治疗先兆流产的潜在靶基因。通过Cytoscape3.7.2软件构建主要活性成分-潜在治疗靶基因网络;利用STRING数据库构建蛋白互做网络;运用在线网站对作用靶基因进行GO功能和KEGG通路富集分析,同时使用SYBYL软件V2.0进行分子对接验证。结果黄芩-白术活性成分-先兆流产疾病靶点网络包含43个化合物,46个靶点和20条通路,主要化合物包括黄芩中的黄连素、汉黄芩、黄芩素等化合物,白术中的α-香树脂醇,关键靶点涉及IL6、VGFR、MMP9、FOS、MAPK14、ESR1等;共同靶点基因功能偏向蛋白质磷酸化的积极调节、炎症反应、凋亡信号通路、血管形态、血管发育等;重要的KEGG通路涉及IL-17信号通路、MAPK信号通路、凋亡通路、TNF信号通路、PI3K/Akt信号通路、雌激素信号通路。分子对接结果显示,黄芩新素、二甲氧基黄酮、麝香黄酮、三甲氧基黄酮、豆甾醇、红花素、黄芩素等15种主要活性成分与HSP90AA1、PPARG、PTGS2结合较好。结论黄芩-白术可能通过多成分、多靶点和多通路协同作用发挥抗感染、营养支持、调节激素水平作用,从而治疗先兆流产。

Objective To explore the potential mechanism of Scutellariae Radix-Atractylodis Macrocephalae Rhizoma medicinal pair in the treatment of threatened abortion based on network pharmacology and molecular docking method.Methods TCMSP database was used to retrieve the active components of Scutellariae Radix-Atractylodis Macrocephalae Rhizoma,and predict the potential target genes.Target genes related to threatened abortion were obtained from GeneCard,NCBI,OMIM,DrugBank,and DisGeNET databases,and the intersection of the two was taken to obtain potential target genes in the Scutellariae Radix-Atractylodis Macrocephalae Rhizoma for the treatment of threatened abortion.Cytoscape 3.7.2 was used to construct the active component-potential target gene network.The GO function enrichment and KEGG pathway analysis of the target protein were carried out by Metascape.SYBYL software(V2.0)was ued to perform molecular docking verification.Results A total of 43 compounds,46 targets,and 20 pathways were included in target network of Scutellariae Radix-Atractylodis Macrocephalae Rhizoma medicinal pair in the treatment of threatened abortion.The main compounds included berberine,wogonin,baicalein and other compounds in Scutellariae Radix,andα-aromatic alcohol compounds in Atractylodis Macrocephalae Rhizoma.The key targets involved IL6、VGFR、MMP9、FOS、MAPK14、ESR1 etc.The common target gene function was biased towards the active regulation of protein phosphorylation,inflammation,apoptosis signaling pathways,vascular morphology,vascular development,etc.The important KEGG pathways involved IL-17 signaling pathway,MAPK signaling pathway,apoptosis pathway,TNF signaling pathway,PI3K/Akt signaling,and estrogen signaling pathway.Molecular docking results showed that 15 main active components,such as baicalein,dimethoxyflavone,musk flavone,trimethoxyflavone,stigmasterol,safflower and baicalein,combined well with HSP90AA1,PPARG and PTGS.Conclusion Scutellariae Radix-Atractylodis Macrocephalae Rhizoma may play the role of anti-infection,nutritional support and hormone regulation through the synergism of multi-component,multi-target and multi-path to treat threatened abortion.