基于网络药理学的芹菜子活性成分抗肝纤维化作用机制研究

Study on Mechanism of Active Compounds of Celery Seed in the Treatment of Liver Fibrosis Based on Network Pharmacology

关键词:  网络药理学  芹菜子  肝纤维化  作用机制

Key words:  network pharmacology  celery seed  liver fibrosis  mechanism

摘要:

目的 构建芹菜子活性成分-作用靶点网络和蛋白相互作用网络，对靶点涉及的功能和通路进行分析，初步探讨芹菜子抗肝纤维化的作用机制。方法 通过中药系统药理学分析平台（TCMSP）、文献挖掘和笔者所在实验室已有研究获取芹菜子主要活性成分，SwissTargetPrediction平台和BATMAN-TCM数据库获取成分靶点，利用GeneCards和OMIM数据库预测和筛选肝纤维化相关的作用靶点。采用Cytoscape软件构建活性成分-作用靶点网络，String数据库和Cytoscape软件绘制蛋白相互作用网络。采用生物学信息注释数据库（DAVID）对靶点进行基因本体（GO）分类富集分析及京都基因与基因组百科全书（KEGG）代谢通路富集分析，结合相关文献分析芹菜子抗肝纤维化的作用机制。结果 筛选得到芹菜子17个活性成分，涉及69个作用靶点。网络分析结果表明，芹菜子主要涉及胶原蛋白分解代谢、炎症反应和胆固醇合成等生物过程，通过调节TGF-β1、NF-κB和PI3K/AKT等信号通路来发挥抗肝纤维化作用。结论 本研究体现了芹菜子多成分-多靶点-多途径的作用特点，其所作用的多条信号通路均存在直接或间接关联性，为进一步研究提供了新思路和新方法。

Abstract:

OBJECTIVE To explore the anti-liver fibrosis mechanism of celery seed through establishing the active components-targets network and protein interactions network and analyzing the functions and pathways of targets. METHODS The active ingredients of celery seed were obtained by TCMSP, literature study and previous work of the laboratory which author study in. SwissTargetPrediction and BATMAN-TCM databases were used to obtain the targets of constituent, GeneCards and OMIM databases were used to predict and screen the targets associated with liver fibrosis. The Cytoscape software was used to construct the active components-targets network. The protein-protein interaction network was constructed by using the String database and Cytoscape software. The GO and KEGG pathways involved in the targets were analyzed by DAVID, and the mechanism of anti-liver fibrosis of celery seed was analyzed in combination with relevant literatures. RESULTS The results showed that 17 active components and 69 targets of celery seed were involved. The network results showed that celery seed was mainly involved in the process of collagen catabolic, inflammatory response and negative regulation of cholesterol storage, by adjusting the TGF-β1, NF-κB, PI3K/AKT and other signaling pathways to exert anti-liver fibrosis effect. CONCLUSION This study reflects the characteristics of multicomponent, multitarget and multipathway of celery seed, and multiple signaling pathways which it act on are correlated with each other, providing new ideas and methods for further research.