UHPLC-TOF-MS结合网络药理学与分子对接探讨人参-酸枣仁药对治疗帕金森的作用机制

Mechanism of Ginseng-Semen Ziziphi Spinosae in treatment of Parkinson's disease based on UHPLC-TOF-MS, network pharmacology and molecular docking

关键词:  帕金森  人参—酸枣仁药对  网络药理学  UHPLC-TOF-MS  分子对接

Key words:  Parkinson"s disease  Ginseng-Semen Ziziphi Spinosae  Network pharmacology  UHPLC-TOF-MS  Molecular docking

摘要:

目的:基于超高效液相色谱串联飞行时间质谱(UHPLC-TOF-MS)、网络药理学及分子对接技术,探讨人参—酸枣仁药对治疗帕金森的作用机制。方法:采用UHPLC-TOF-MS对人参—酸枣仁药对入血成分进行定性分析。采用SwissTargetPrediction、GeneCards等数据库获取入血成分及疾病相关靶点,取交集后构建蛋白互作(PPI)网络,筛选核心靶点并进行GO功能和KEGG通路富集分析。采用Cytoscape 3.10.0软件构建“化合物-靶点-通路”网络,预测人参—酸枣仁药对治疗帕金森的作用靶点。采用AutoDock软件对关键靶点及活性成分进行分子对接验证。结果:共鉴定人参—酸枣仁药对入血成分20个,主要包含三萜皂苷类、生物碱类等化合物。靶蛋白相互作用(PPI)分析筛选关键靶点78个,KEGG富集分析发现人参—酸枣仁药对可能通过PI3K-Akt、Rap1、Prolactin等信号通路发挥治疗帕金森的作用。分子对接结果显示,关键靶点MAPK1、AKT1、MAPK8、HRAS、EGFR与人参—酸枣仁药对中活性成分人参炔B、人参皂苷Rg1、酸李碱、人参皂苷Rf、莲心季铵碱结合良好。结论:人参—酸枣仁药对可通过多成分、多靶点、多通路协同发挥治疗帕金森的作用。

Abstract:

Objective: To explore the mechanism of Ginseng-Semen Ziziphi Spinosae in treatment of Parkinson"s disease based on UHPLC-TOF-MS, network pharmacology and molecular docking technologies. Methods: UHPLC-TOF-MS was used to qualitatively identify the constituents of Ginseng-Semen Ziziphi Spinosae migrated into blood. Targets of the plasma constituents and the disease were retrieved from SwissTargetPrediction and GeneCards. Then the protein-protein interaction (PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.10.0 was employed to construct the “compound-target-pathway” network and the targets of Ginseng-Semen Ziziphi Spinosae against Parkinson"s disease were predicted. The AutoDock software was used for molecular docking analysis of key targets and active ingredients. Results: A total of 20 constituents of Ginseng-Semen Ziziphi Spinosae migrated into blood were identified, mainly including triterpenoid saponins and alkaloids. 78 key targets were screened out by protein-protein interaction (PPI). KEGG enrichment showed that Ginseng-Semen Ziziphi Spinosae might play a role in treatment of Parkinson"s disease through PI3K-Akt, Rap1, Prolactin and other pathways. Molecular docking results showed that key targets MAPK1, AKT1, MAPK8, HRAS, EGFR could be well combined by core active constituents Ginsenoyne B, Ginsenoside Rg1, Zizyphusine, Ginsenoside Rf, Lotusine, respectively. Conclusions: Ginseng-Semen Ziziphi Spinosae can play a role in the prevention and treatment of Parkinson"s disease through multiple components, targets and pathways.