UPLC-Q-TOF-MS、GC-MS联合网络药理学及分子对接技术分析经典名方清胃散治疗牙周炎的作用机制

Mechanism of Qingwei Powder in treatment of periodontitis based on UPLC-Q-TOF-MS,GC-MS,network pharmacology and molecular docking

基于色谱-质谱和网络药理学-分子对接技术分析经典名方清胃散治疗牙周炎的作用机制。利用UPLC-Q-TOF-MS、GC-MS技术分析清胃散化学成分;经TCMSP数据库筛选清胃散活性成分及靶蛋白后利用SwissTargetPrediction数据库进行靶点预测;利用GeneCards、OMIM和DisGeNET数据库获取牙周炎相关治疗靶点;运用Venny 2.1构建韦恩图并得到交集靶点,运用Cytoscape 3.7.2构建“化合物-靶点-疾病”网络;利用clusterProfiler R功能包对潜在作用靶点进行GO功能和KEGG通路富集分析,构建“化合物-靶点-通路”网络,并利用分子对接技术验证活性成分与靶点蛋白的结合活性。通过色谱-质谱技术共分析得到清胃散中189种化学成分,筛选后得到39种活性成分对应180个潜在作用靶点与牙周炎相关,活性成分作用靶点富集分析得到92条KEGG通路,“化合物-靶点-通路”网络共涉及20条KEGG通路、34种活性成分和99个靶点,分子对接结果验证关键化合物与关键靶点有较好结合力。该研究初步表明,经典名方清胃散通过多成分、多靶点、多途径发挥治疗牙周炎的作用,体现了中药复杂系统的作用特点,为清胃散后续的物质基准及关键质量属性研究提供了理论依据。

The present study explored the mechanism of Qingwei Powder(QP)in the treatment of periodontitis based on chromatography-mass spectrometry and network pharmacology-molecular docking techniques.UPLC-Q-TOF-MS and GC-MS were used to identify the chemical constituents of QP.The active components and targets were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and their targets were predicted using SwissTargetPrediction.Targets related to periodontitis were obtained from GeneCards,OMIM,and DisGeNET.Venn diagram was constructed using Venny 2.1 to obtain the intersection targets.Cytoscape 3.7.2 was used to construct the"chemical component-target-disease"network.The targets were analyzed for Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment by clusterProfiler R,and the"chemical component-target-pathway"network was constructed.The binding activity of the active components to the target proteins was verified by molecular docking.A total of 189 chemical components were obtained by UPLC-Q-TOF-MS and GC-MS,including 39 active components with 180 potential targets related to periodontitis.Target enrichment analysis of the active components yielded 92 KEGG pathways.Twenty KEGG pathways,34 active components,and 99 targets were involved in the"chemical component-target-pathway"network.Molecular docking verified a good binding ability of the key targets to the key compounds.This study preliminarily indicates that QP is effective in treating periodontitis through multiple components,multiple targets,and multiple pathways,which reflects the complex system of Chinese medicine.This study provides the theoretical foundation for the subsequent research on the material basis and key quality attributes of QP.