健脾清热活血方治疗大肠癌作用机制的网络药理学研究  

Mechanism of Jianpi Qingre Huoxue Decoction in Treatment of Colorectal Cancer Based on Network Pharmacology and Bioinformatics

作　　者：黄李冰雪 钟婵 陈远能[2] 张涛[2] HUANG Libingxue;ZHONG Chan;CHEN Yuanneng;ZHANG Tao(Guangxi University of Chinese Medicine,Nanning 530000 Guangxi,China;Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530000 Guangxi,China)

机构地区：[1]广西中医药大学,广西南宁530000 [2]广西中医药大学附属瑞康医院,广西南宁530000

出　　处：《中药新药与临床药理》2020年第9期1045-1051,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81260536);广西自然科学基金项目(2018GXNSFAA281042);广西一流学科建设重点项目(2018XK082)。

摘　　要：目的基于网络药理学方法探讨健脾清热活血方治疗大肠癌的作用机制。方法通过TCMID、TCMSP数据库筛选健脾清热活血方的化学成分,并预测相关靶点,导入Cytoscape 3.7.0软件,构建"活性化合物-靶点"网络并进行分析。利用OMIM、Gene Cards及DisGeNET数据库筛选大肠癌相关疾病靶点,并与活性成分靶点取交集作为健脾清热活血方治疗大肠癌的潜在作用靶点;利用STRING构建潜在作用靶点PPI网络,分析并获得核心治疗靶点。将核心治疗靶点与活性成分进行分子对接并验证;利用David数据库对核心治疗靶点进行GO生物学功能及KEGG通路富集分析。结果共筛选出健脾清热活血方145个活性成分、372个对应靶点,以及119个药物成分-疾病共同靶点。排名前5位的核心治疗靶点SRC、PIK3CA、AKT1、MAPK1、STAT3与145个活性化合物进行分子对接显示有很强的结合能力。生物功能注释及KEGG分析显示,健脾清热活血方参与调节凋亡、蛋白质磷酸化、细胞增殖、信号转导、细胞迁移等生物过程及PI3K-AKT信号通路、Rap1信号通路及HIF-1信号通路等。结论健脾清热活血方可能通过SRC、PIK3CA、AKT1、MAPK1、STAT3等核心治疗靶点,以及PI3K-AKT、Rap1、HIF-1等信号通路发挥治疗大肠癌的作用。Objective By using network pharmacology and bioinformatics technology,to constructed the "componenttarget-pathway" network relationship of Jianpi Qingre Huoxue decoction in the treatment of colorectal cancer,and discuss the pharmacological mechanism of Jianpi Qingre Huoxue decoction in the treatment of colorectal cancer.Methods The chemical constituents of Jianpi Qingre Huoxue decoction were screened by TCMID and TCMSP,and the related targets were predicted and collected.The network of "active components-targets was constructed and analyzed by introducing into Cytoscape.OMIM,Gene Cards and DisGeNET databases were used to screen colorectal cancer related targets,and the common targets with active component targets were chosen as potential therapeutic targets.The therapeutic target PPI network was constructed by STRING,and the core therapeutic targets were obtained by analysis.The core therapeutic targets were docked with the active components and verified by molecular docking,and the biological function and KEGG pathway enrichment of the therapeutic targets were analyzed by David.Results A total of 145 active components,372 corresponding targets and 119 targets related to the treatment of colorectal cancer were obtained.Molecular docking showed that the active components have a strong ability to bind to therapeutic targets.Biological function annotation and KEGG analysis showed that it was involved in the regulation of apoptosis,protein phosphorylation,cell proliferation,signal transduction,cell migration and PI3 K-AKT signaling pathway,Rap1 signaling pathway,HIF-1 signaling pathway and so on.Conclusion Jianpi Qingre Haoxue decoction may be active in treatment of colorectal cancer via acting on core targets such as SRC,PIK3 CA,AKT1,MAPK1,and STAT3,and involving PI3 K-AKT,Rap1,HIF-1 signaling pathways.This paper preliminarily reveals the material basis and multi-component,multi-target and multi-pathway mechanism of Jianpi Qingre Huoxue decoction in the treatment of colorectal cancer,which provides a new research id

关 键 词：网络药理学 健脾清热活血方 大肠癌 信号通路 分子对接 靶点 作用机制 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]