摘要
目的使用网络药理学和网络分析技术探究川芎-黄连药对改善动脉粥样硬化的潜在活性成分及可能作用机制。方法利用TCMSP平台及文献挖掘收集川芎和黄连的主要活性成分,于PubChem数据库获得主要活性成分的结构式,利用Swiss Target Prediction平台对活性成分的潜在作用靶点进行预测后,与GeneCards数据库中获得的动脉粥样硬化相关靶点基因于Cytoscape中绘制药物-活性成分-疾病-靶点基因网络图,最后利用FunRich软件及Cytoscape中的Clue Go插件分别进行生物学过程和信号通路的基因富集分析。结果经筛选得到主要活性成分共27个,其中川芎成分13个,黄连成分14个,收集到改善动脉粥样硬化的潜在靶点基因170个,主要包括MBNL1、BCHE、ACHE、CHRM1、CHRM4、MBNL3、MBNL2等。基因富集分析结果显示川芎-黄连药对改善动脉粥样硬化的16条信号通路主要包括钙离子信号通路、环磷酸腺苷(cAMP)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、胰岛素抵抗、胰岛素分泌、醛固酮分泌与合成等信号通路。主要生物学进程则包括G蛋白偶联受体介导的信号通路、碳酸氢盐转运、脂氧合酶途径、多不饱和脂肪酸生物合成途径、氧化还原进程等。结论基于网络药理学方法挖掘发现川芎-黄连药对多途径、多靶点改善动脉粥样硬化的作用机制。
Objective To explore the potential active components and underlying mechanism of Ligusticum Chuanxiong Hort and Coptidis Rhizoma on attenuating atherosclerosis based on network pharmacology and network analysis techniques.Methods Active components were collected from Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and relevant literatures.Structural formulas of above components were obtained from PubChem database and further analysed by Swiss Target Prediction.Targets related to atherosclerosis were collected from GeneCards database.Drug-active component-target-disease network was established by Cytoscape software.And gene enrichment analysis including biological process and biological pathway was fulfilled by Clue Go plug-in and FunRich software,respectively.Results Twenty-seven main active components were screened out,with 13 components in Ligusticum Chuanxiong Hort,and 14 components in Coptidis Rhizoma.Moreover,170 potential targets were collected,including MBNL1,BCHE,ACHE,CHRM1,CHRM4,MBNL3,MBNL2.The results of gene enrichment analysis showed Ligusticum Chuanxiong Hort and Coptidis Rhizoma could attenuate atherosclerosis through 16 pathways,including calcium signaling pathway,cyclic adenosine monophosphate(cAMP)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,insulin resistance,insulin secretion and aldosterone-regulated sodium reabsorption.Biological process included G-protein coupled receptor signaling pathway,bicarbonate transport,lipoxygenase pathway,hepoxilin biosynthetic process and oxidation-reduction process.Conclusion This research revealed that Ligusticum Chuanxiong Hort and Coptidis Rhizoma attenuated atherosclerosis in multi-component,multi-target based on network pharmacological methods.
作者
赵艺涵
赖润民
史大卓
张莹
ZHAO Yihan;LAI Runmin;SHI Dazhuo;ZHANG Ying(School of Graduate,Beijing University of Chinese Medicine,Beijing 100029,China;Institute of Cardiovascular Research,Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China)
出处
《中西医结合心脑血管病杂志》
2020年第11期1677-1683,共7页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金青年项目(No.81703927)。
关键词
动脉粥样硬化
网络药理学
川芎
黄连
靶点基因
作用机制
atherosclerosis
network pharmacology
Ligusticum Chuanxiong Hort
Coptidis Rhizoma
target gene
mechanism of action
