基于网络药理学和分子对接技术探讨异功散治疗小儿厌食症的作用机制

Mechanism of Yigongsan in treatment of pediatric anorexia based on network pharmacology and molecular docking

目的 通过网络药理学和分子对接技术探讨异功散治疗小儿厌食症的主要成分及作用机制。方法 通过TCMSP数据库查找异功散中口服利用度和类药性符合要求的化合物,并通过PubChem、UniProt数据库获得其已知靶点。通过GeneCards、OMIM、NCBI Gene、DisGeNET、TTD数据库获得小儿厌食症相关靶点。将异功散和小儿厌食症靶点取交集,并构建蛋白质相互作用(PPI)网络。通过中心度值、紧密中心度值、节点连接度值进一步筛选出关键靶点。将关键靶点蛋白进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。采用PyMOL和AutoDock Vina软件将关键靶点和化合物进行分子对接。结果 异功散中共获得139个符合条件的化合物,相对应781个靶点,小儿厌食症共获得靶点2 278个,二者交集为369个靶点。通过PPI网络构建得到66个关键靶点,关键靶点的GO功能注释和KEGG通路富集分析得出生长因子应答、转录调节、癌症通路和蛋白磷酸化通路等生化过程和信号通路与异功散治疗小儿厌食症具有相关性。分子对接结果表明山柰酚、槲皮素、柚皮素、戈米辛B、12-异戊烯酰基-2E,8E,10E-白术三醇与甘油醛-3-磷酸脱氢酶(GAPDH)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、白蛋白(ALB)、P53核内磷酸化蛋白(TP53)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)等靶点具有较好结合能力。结论 异功散通过调节丝裂原活化蛋白激酶(MAPK)、核因子-κB(NF-κB)、生长因子、癌症、蛋白磷酸化等相关的信号通路来实现对胃肠道消化功能和肠道菌群的调节从而治疗小儿厌食症。

Objective To explore the main ingredients and mechanism of Yigongsan in treatment of pediatric anorexia through network pharmacology and molecular docking technology. Methods Compounds that met the requirements of oral availability and drug-like properties in Yigongsan were searched through TCMSP database, and their targets were obtained through PubChem, UniProt databases. Targets related to pediatric anorexia were obtained through Gene Cards, OMIM, NCBI Gene, Dis Ge NET and TTD databases. The intersection of Yigongsan and pediatric anorexia targets was obtained and protein-protein interaction network(PPI)was constructed. Key targets were further screened by betweenness centrality, closeness centrality, and degree. Key target proteins were analyzed for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway functional enrichment.Py MOL and AutoDock Vina software were used to conduct molecular docking between key targets and compounds. Results A total of 139 qualified compounds were obtained from Yigongsan corresponding to 781 targets, and 2 278 targets were obtained from pediatric anorexia. The intersection of the two was 369 targets. A total of 66 key targets were obtained through the PPI network. The GO functional annotation and KEGG pathway enrichment analysis of key targets showed that biochemical processes and signaling pathways such as growth factor response, transcriptional regulation, cancer pathway and protein phosphorylation pathway were correlated with the treatment of pediatric anorexia by Yigongsan. The molecular docking results showed that kaempferol, quercetin,naringenin, gomisin B, 12-senecioyl-2E,8E,10E-atractylentriol had good binding ability to GAPDH, AKT1, ALB, TP53, TNF, IL-6 and other targets. Conclusion Yigongsan can regulate gastrointestinal digestive function and intestinal flora by regulating MAPK, NF-κB, growth factor, cancer, protein phosphorylation and other related signal pathways to treat pediatric anorexia.