基于网络药理学和分子对接的芪黄通秘软胶囊治疗便秘的作用机制研究

Mechanism of Qihuang Tongmi Soft Capsules in the Treatment of Constipation Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学和分子对接技术,探讨芪黄通秘软胶囊治疗便秘的作用机制。方法:依托中药系统药理学数据库与分析平台、TCM Database@Taiwan等数据库,检索芪黄通秘软胶囊中11味中药的化学成分及其靶点,构建成分-靶点网络,通过DrugBank、GeneCards等数据库检索便秘相关靶点,依托STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并利用DAVID数据库对关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,使用R语言进行结果可视化,将药物关键化学成分与核心靶点导入AutoDockTools 1.5.7软件计算其结合能并进行分子对接。结果:共筛选出124个化学成分和113个疾病靶点,槲皮素、山柰酚等成分在网络中处于关键地位;PPI网络中度值排序居前3位的蛋白分别为蛋白激酶B1、肿瘤蛋白p53和表皮生长因子受体;GO功能富集分析结果显示,102个条目中,有55个涉及生物过程,31个涉及分子功能,16个涉及细胞组分;KEGG通路富集分析结果显示,115个通路主要集中在内分泌耐药、丝裂原激活的蛋白激酶信号通路上;分子对接结合能均<-20.92 kJ/mol。结论:本研究揭示了芪黄通秘软胶囊治疗便秘的部分机制,为深入开展芪黄通秘软胶囊的临床相关研究及应用提供了参考和借鉴。

OBJECTIVE:To probe into the mechanism of Qihuang Tongmi soft capsules in the treatment of constipation through network pharmacology and molecular docking.METHODS:Based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and TCM Database@Taiwan and other databases,the chemical components and its targets of the 11 traditional Chinese medicines in Qihuang Tongmi soft capsules were retrieved,the component-target network was constructed,the constipation-related targets were retrieved through DrugBank,GeneCards and other databases,the protein-protein interaction(PPI)network was constructed by STRING database,the Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on key targets were conducted by using DAVID database,the results visualization was performed by using R language,the key chemical components and core targets were imported into the AutoDockTools 1.5.7 software to calculate its binding energy and molecular docking.RESULTS:A total of 124 chemical components and 113 disease targets were screened out,the quercetin and kaempferol were the key components in the network;the top 3 proteins ranked by degree value in the PPI network were protein kinase B1,tumor protein p53 and epidermal growth factor receptor,respectively.The GO functional enrichment analysis showed that,of the 102 entries,55 were related to biological processes,31 were related to molecular functions,and 16 were related to cellular components.KEGG pathways enrichment analysis showed that 115 pathways were mainly concentrated on endocrine drug-resistance and mitogen-activated protein kinase signaling pathways;all the binding energy of molecular docking were<-20.92 kJ/mol.CONCLUSIONS:This research reveals partial mechanism of Qihuang Tongmi soft capsules in the treatment of constipation,which provides references for the in-depth development of clinical research and application of Qihuang Tongmi soft capsules.