天麻治疗动脉粥样硬化作用机制探讨  

Mechanism of therapeutic effect of Tianma(Gastrodia elata Blume)on atherosclerosis

作　　者：程江豪 陈普 杨丽萍 段小花 CHENG Jianghao;CHEN Pu;YANG Liping;DUAN Xiaohua(Yunnan Key Laboratory of Dai and Yi Medicines,Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学民族医药学院、云南省傣医药与彝医药重点实验室,昆明650500

出　　处：《山东医药》2023年第26期15-19,共5页Shandong Medical Journal

基　　金：云南省傣医药与彝医药重点实验室开放课题(202210SS2201);兴滇英才支持计划—青年人才专项(XDYC-QNRC-2022-0284);国家中医药管理局高水平中医药重点学科建设项目“傣医学”“傣药学”。

摘　　要：目的 基于网络药理学、分子对接技术探讨天麻治疗动脉粥样硬化(AS)的作用机制。方法 在ETCM和TCMIP数据库中检索天麻的有效活性成分,将其导入Swiss Target Prediction数据库筛选天麻活性成分的潜在作用靶点;通过Gene Cards、Drug Bank、OMIM和TTD数据库获取AS的疾病相关靶点;二者取交集,获得药物—疾病交集靶点。通过STRING数据库和Cyto Scape软件构建天麻治疗AS的有效活性成分—靶点调控网络和PPI蛋白网络互作图,并对网络进行拓扑分析,获得天麻的关键活性成分和药物—疾病核心靶点。对药物—疾病交集靶点进行GO和KEGG富集分析,获得天麻治疗AS中可能参与的生物学进程及信号通路。通过分子对接技术验证天麻关键活性成分与药物—疾病核心靶点蛋白的结合能力。结果 共获得天麻治疗AS的97个药物—疾病交集靶点。经过拓扑分析,筛选出药物—疾病核心靶点AKT1、PTGS2、PPARG、CASP3、ESR1。对97个药物—疾病交集靶点进行GO和KEGG通路分析,主要富集于癌症通路、血清素能突触、脂质和AS、PPAR信号通路等。以药物—疾病核心靶点AKT1、PTGS2、PPARG、CASP3、ESR1为受体,以天麻关键活性成分棕榈酸、双酚F、4-乙氧基甲基苯基-4’-羟基苯基醚、对羟基苄基乙醚及4-(4’-羟基苄氧基)苄基甲醚为配体进行分子对接,结果显示,双酚F、4-乙氧基甲基苯基-4’-羟基苯基醚、4-(4’-羟基苄氧基)苄基甲醚与药物—疾病核心靶点AKT1、PTGS2、PPARG、CASP3、ESR1的结合能<-7.0 kcal/mol。结论 天麻可能通过双酚F、4-乙氧基甲基苯基-4’-羟基苯基醚等关键活性成分作用于PTGS2、ESR1等靶点,通过抗炎、抗氧化应激、降脂与抗凋亡等途径,调节癌症通路、脂质和动脉粥样硬化通路、PPAR信号通路等通路,发挥其抗AS作用。Objective To explore the mechanism of action of Tianma(Gastrodia elata Blume)in the treatment of atherosclerosis(AS)based on network pharmacology and molecular docking technology.Methods The effective active ingredients of Tianma were searched in ETCM and TCMIP databases,and were imported into Swiss Target Prediction data⁃base to screen the potential targets of Tianma active ingredients;the disease-related targets of AS were obtained through Gene Cards,Drug Bank,OMIM and TTD databases;and the intersection of the two was taken to obtain the drug-disease intersection targets.The STRING database and CytoScape software were used to construct the active ingredient-target regu⁃latory network and PPI protein network interactions of Tianma for the treatment of AS,and the network was analyzed by to⁃pology analysis to obtain the key active ingredients of Tianma and drug-disease core targets.The drug-disease intersection targets were analyzed by GO and KEGG enrichment to obtain the biological processes and signaling pathways that might be involved in the treatment of AS by Tianma.The binding ability of the key active ingredients of Tianma to the drug-disease core target proteins was verified by molecular docking technology.Results Ninety-seven drug-disease intersection tar⁃gets were obtained for the treatment of AS by Tianma.After topological analysis,the drug-disease core targets AKT1,PTGS2,PPARG,CASP3,and ESR1 were screened out.Ninety-seven drug-disease intersection targets were subjected to GO and KEGG pathway analysis,and were mainly enriched in pathways in cancer,serotonergic synapse,lipid and atherosclerosis,and PPAR signaling pathway,etc.The drug-disease core targets AKT1,PTGS2,PPARG,CASP3,and ESR1 were used as receptors,and palmitic acid,bisphenol F,4-ethoxymethylphenyl-4'-hydroxybenzyl ether,P-hydroxybenzyl ethyl ether,and 4-(4'-hydroxybenzyloxy)benzyl methyl ether,a key active ingredient of Tianma,as ligands were used for molecular docking.The results showed that bisphenol F,4-ethoxymethylphenyl-4'-hydroxy

关 键 词：天麻 动脉粥样硬化 环加氧酶2 双酚F 网络药理学 分子对接 

分 类 号：R543.5[医药卫生—心血管疾病]