基于网络药理学的枳实挥发油治疗慢性传输型便秘的机制研究

该文旨在通过构建枳实挥发油活性成分-作用靶点网络图及蛋白相互作用(PPI)网络图,分析靶点涉及的功能和通路,探讨枳实挥发油治疗慢性传输型便秘(slow transit constipation,STC)的作用机制。利用气相色谱-质谱联用仪(GC-MS)检测枳实挥发油的化学成分;利用PubChem,TCMSP,STITCH,Swiss Target Prediction检索枳实挥发油成分的靶点,通过OMIM,Genecards-Search Resuits,TTD预测和筛选STC的作用靶点;通过Cytoscape 3.7.1构建活性成分-作用靶点和PPI网络图,利用BioGPS数据库对靶点对应的组织分布进行分析,利用R语言进行GO功能、KEGG通路的富集分析,通过Discovery Studio 2.5软件对成分与靶点进行分子对接验证。最终,共检测到枳实挥发油化合物15个,共预测出115个枳实挥发油治疗STC的共同作用靶点。GO富集分析显示枳实挥发油的活性主要涉及血液循环、循环系统、类固醇激素反应、信号通路等生物学过程。KEGG富集通路共23条,其中神经活性配体-受体相互作用、cAMP信号通路、内分泌抵抗、Ca^2+信号通路、5-羟色胺能突触等通路对STC有显著作用,分子对接结果表明发挥治疗STC的相关靶蛋白有(ACHE,PTGS2,SLC6A2,CNR2)。通过网络药理学揭示了枳实挥发油的多组分、多靶点、多通路的特点,为进一步研究枳实挥发油治疗STC的作用机制提供了新的思路和方法。

Mechanism of Aurantii Fructus Immaturus volatile oil in treatment of slow transit constipation based on network pharmacology

To construct the active component-action target network diagram and protein-protein interaction(PPI) network diagram of Aurantii Fructus Immaturus volatile oil, so as to explore the mechanism of Aurantii Fructus Immaturus volatile oil in the treatment of slow transit constipation(STC) by analyzing the functions and pathways involved in the target. The chemical constituents of Aurantii Fructus Immaturus volatile oil were determined by gas chromatography-mass spectrometry(GC-MS). The targets of Aurantii Fructus Immaturus volatile oil were studied by PubChem, TCMSP, STITCH and Swiss Target Prediction. OMIM, Genecards-Search Resuits and TTD were used to screen out the targets of Slow Transit Constipation. The active component-action targets and PPI network diagram were constructed by Cytoscape 3.7.1. The target organ distribution was analyzed by BioGPS database. GO and KEGG pathways involved in the targets were analyzed by R language. The molecular docking between the components and the targets was verified by Discovery Studio 2.5 software. Finally, 15 volatile oil compounds from Aurantii Fructus Immaturus were detected, and 115 targets of volatile oil in the treatment of STC were predicted. GO enrichment analysis showed that the activity of Aurantii Fructus Immaturus volatile oil mainly involved blood circulation, circulation system process, response to steroid hormone, signal release and other biological processes. There were 23 KEGG enrichment pathways, among which Neuroactive ligand-receptor interaction, cAMP signaling pathway, Endocrine resistance, Calcium signaling pathway and Serotonergic synapse pathways played a significant role in STC. The results of molecular docking showed that relevant target proteins for the treatment of STC were ACHE, PTGS2, SLC6 A2 and CNR2.The multi-component, multi-target and multi-pathwaycharacteristics of Aurantii Fructus Immaturus volatile oil were revealed by network pharmacology, which provided a new therapeutic idea and method for the further study of the mechanism of Aurantii Fructus Immaturus volatile oil in the treatment of STC.