Mechanism of volatile oil from Chuanxiong(Chuanxiong Rhizoma)-Suhexiang(Styrax)-Bingpian(Borneolum)in treating angina pectoris based on network pharmacology and its protective effects on myocardial damage in rats  

基于网络药理学探究“川芎-苏合香-冰片”组方挥发油治疗心绞痛作用机制及其对心肌受损大鼠的保护作用

作　　者：LEI Zhiqiang WANG Chaoping Abid Naeem YIN Ning CAO Meifang LUO Jing 雷志强;王朝平;Abid Naeem;殷宁;曹美芳;罗晶(江西中医药大学临床医学院,江西南昌330006;江西中医药大学药学院,江西南昌330006;The Islamia University of Bahawalpur,Punjab 63100,Pakistan;现代中药制剂教育部重点实验室,江西南昌330006;创新药物与高效节能降耗制药设备国家重点实验室,江西南昌330006)

机构地区：[1]Clinical Medical College of Jiangxi University of Chinese Medicine,Nanchang,Jiangxi 330006,China [2]School of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang,Jiangxi 330006,China [3]The Islamia University of Bahawalpur,Punjab 63100,Pakistan [4]Key Laboratory of Modern Chinese Medicine Preparation,Ministry of Education,Nanchang,Jiangxi 330006,China [5]State Key Laboratory of Innovative Drugs and Pharmaceutical Equipment with High Efficiency,Energy Saving and Consumption Reduction,Nanchang,Jiangxi 330006,China

出　　处：《Digital Chinese Medicine》2021年第3期202-213,共12页数字中医药（英文）

基　　金：funding support from the Major Science and Technology Research and Development Special Project of Jiangxi Science and Technology Department(No.20194ABC28009);National Key Research and Development Plan(No.2018YFC1706404)。

摘　　要：Objective To explore the pharmacodynamic material basis and mechanism of action of volatile oil from Chuanxiong(Chuanxiong Rhizoma)-Suhexiang(Styrax)-Bingpian(Borneolum)(hereinafter referred to as C-S-B volatile oil)in treating angina pectoris based on network pharmacology and to detect its protective effects against rat myocardial damage.Methods Gas chromatography-mass spectrometry(GC-MS)was used to determine the constituents of volatile oils from Chuanxiong(Chuanxiong Rhizoma),Suhexiang(Styrax),and Bingpian(Borneolum),and the targets of the three main constituents were found predicted and screened using the PharmMapper server,and Gene Cards and Coo LGe N databases.The STRING database and Cytoscape software were used to draw the protein-protein interaction(PPI)network,RStudio software was used to analyze Gene Ontology(GO)and Kyoto Encyclopedia of Genome and Genome(KEGG)pathways,and Cytoscape software was used to construct the component-target-pathwaydisease network.The rat model of myocardial injury was established by intraperitoneal injection of a large dose of isoprenaline hydrochloride.After continuous intervention with C-S-B volatile oil for 14 d,the ejection fraction(EF)and short axis shortening rate(FS)of the left ventricle were detected.The indices of myocardial damage were detected after hematoxylin-eosin(HE)staining.Results Fifteen volatile oil components from the C-S-B formula were identified.There are 470 targets of these volatile oil components and 401 angina-related genes.There are 28 core targets,including CHRM4,ADRA1 A,FGFR1,CHRM2,CYP2 A6,CHRM5,CHRM1,CHRM3,HDAC2,and MPO,etc..The results of the KEGG analysis indicated that the C-S-B formula probably interferes with the following pathways:neuroactive ligand-receptor interactions,calcium signaling,cytochrome P450 metabolism of heteropoietin,among others.The results of animal experiments showed that the C-S-B formula essential oil could significantly improve the following myocardial indices in rats with myocardial injury:EF,FS,left ventricular end-sys目的基于网络药理学探讨"川芎-苏合香-冰片"组方挥发油(以下简称C-S-B组方挥发油)治疗心绞痛药效物质基础及其作用机制,并探讨C-S-B组方挥发油对心肌受损的保护作用。方法通过GC-MS测定川芎、苏合香、冰片混合挥发油成分并进行筛选,利用Pharm Mapper、Gene Cards和CoolGe N数据库预测和筛选三者活性成分的作用靶点。采用STRING数据库和Cytoscape软件绘制蛋白相互作用(PPI)网络图,借助Rstudio软件对靶点进行基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路分析,采用Cytoscape软件构建成分-靶点-通路-疾病网络。通过大剂量腹腔注射盐酸异丙肾上腺素建立心肌受损大鼠模型,使用C-S-B组方挥发油连续干预14 d后,分别检测大鼠射血分数(EF)和左心室短轴缩短率(FS)等各项超声心动指标;并通过苏木精-伊红染色法(HE)染色对心肌组织指标检测。结果共收集C-S-B组方挥发油成分15个;C-S-B组方挥发油成分靶点470个;心绞痛相关基因401个;核心靶点有CHRM4、ADRA1A、FGFR1、CHRM2、CYP2A6、CHRM5、CHRM1、CHRM3、HDAC2、MPO等28个。KEGG分析结果主要涉及神经活性配体-受体相互作用,钙离子信号通道,细胞色素P450对异生素的代谢等通路。动物实验结果表明C-S-B组方挥发油可明显改善心肌受损模型大鼠的EF、FS、左心室收缩末内径(LVIDs)、左心室舒张末期内径(LVIDd)、每搏输出量(SV)等心肌指标,且差异均具有统计学意义(P<0.01)。结论本研究从多成分-多靶点-多途径分析C-S-B组方挥发油成分治疗心绞痛的作用机制,为进一步深入揭示其作用机制奠定基础。动物实验表明,C-S-B组方挥发油能够改善心肌受损模型大鼠的EF、FS等指标,从而缓解心功能过分亢进导致的心肌损伤,改善心脏功能,预防心肌损伤。

关 键 词：Chuanxiong(Chuanxiong Rhizoma) Suhexiang(Styrax) Bingpian(Borneolum) Volatile oil Angina pectoris Gas chromatography-mass spectrometry(GC-MS) Network pharmacology Myocardial injury Rat model 

分 类 号：R285.5[医药卫生—中药学]