基于网络药理学和分子对接探究罗布麻叶抗高脂血症的作用机制  

Mechanism Exploration of Apocynum venetum L.leaves in Treatment of Hyperlipidemia Based on Network Pharmacology and Molecular Docking

作　　者：许泽恭 祝晨蔯[1] 周玖瑶[1] 赵钟祥[1] 李瑜[2] 章娟[3] 周园[1] 张蕾[1] XU Zegong;ZHU Chenchen;ZHOU Jiuyao;ZHAO Zhongxiang;LI Yu;ZHANG Juan;ZHOU Yuan;ZHANG Lei(School of Pharmaceutical Science,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;School of Nursing,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Guangzhou Institute for Drug Control,Guangzhou 510160 Guangdong,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006 [2]广州中医药大学护理学院,广东广州510006 [3]广州市药品检验所,广东广州510160

出　　处：《中药新药与临床药理》2021年第8期1154-1163,共10页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81803824);广东省科技计划项目(2016A020226031);广东省自然科学基金项目(2018A030313328)。

摘　　要：目的基于网络药理学和分子对接方法探究罗布麻叶(Apocynum venetum L.leaves,AVL)抗高脂血症的活性成分和分子作用机制。方法依据中药药理学技术平台(TCMSP)数据库、SuperPred webserver、STITCH、SwissTargetPrediction和PharmMapper数据库,筛选罗布麻叶的潜在活性成分、预测潜在作用靶点。从OMIM、DrugBank和GeneCard数据库搜索高脂血症疾病的相关靶点信息,由Cytoscape生物信息分析软件构建“分子-靶点-疾病”网络。在String数据库中构建蛋白互作网络并在Cytoscape中进行可视化。采用Cytoscape和Bioconductor数据库分别对交集靶点进行GO和KEGG通路富集分析,最终采用分子对接进行初步验证。结果筛选出罗布麻叶中金丝桃苷、槲皮素和山柰酚等28个活性成分,作用于丝氨酸/苏氨酸蛋白激酶(AKT1)、肿瘤蛋白P53(TP53)和丝裂原活化蛋白激酶3(MAPK3/ERK1)等129个潜在靶点,GO分析发现罗布麻叶治疗高脂血症的潜在靶点主要参与压力应激、脂质代谢和类固醇代谢等生物过程,KEGG通路分析主要涉及流体剪切应力与动脉粥样硬化、IL-17和AGE-RAGE等信号通路。分子对接结果表明潜在活性成分和AKT1、TP53和MARK3等关键靶蛋白均能稳定结合。结论本研究初步阐述了罗布麻叶抗高脂血症的作用机制,发现其通过脂质生物合成、炎症反应调控和氧化应激等过程发挥治疗高脂血症的作用。Objective To explore the active compounds and integrative mechanism of Apocynum venetum L.leaves(AVL)in treatment of hyperlipidemia by using network pharmacology and molecular docking.Methods According to Traditional Chinese Medicine System Pharmacology Technology Platform(TCMSP)database,SuperPred webserver,Swiss Target Prediction,STITCH and PharmMapper database,the potential active ingredients of AVL were screened and the potential targets of action were predicted.The targets of hyperlipidemia were obtained from OMIM,Drug Bank and GeneCard databases,and the compound-target-disease interaction network was built using Cytoscape3.7.2.The protein-protein interaction network was erected in the STRING database and visualized through Cytoscape.Then,Cytoscape and Bioconductor databases were respectively utilized for performing GO and KEGG pathway enrichment analysis on the intersectional targets.Finally,molecular docking was used for preliminary verification.Results 28 active ingredients including hyperoside,quercetin and kaempferol in AVL,as well as 129 potential targets,such as serine/threonine protein kinase(AKT1),tumor P53(TP53)and mitogen activated protein kinase 3(MAPK3/ERK1)were screened out.GO analysis found that the potential targets of AVL in treatment of hyperlipidemia were mainly involved in biological processes including response to stress,lipid metabolism and steroid metabolism.KEGG pathway analysis mainly involved fluid shear stress and atherosclerosis,IL-17 signaling pathway and AGE-RAGE signaling pathway,etc.The molecular docking results indicated that the potential active ingredients could bind stably to key proteins such as AKT1,TP53 and MARK3.Conclusion This study preliminarily explained the mechanism of AVL in the treatment of hyperlipidemia.We found that AVL exerts anti-hyperlipidemia activity through regulating lipid biosynthesis,inflammatory response and oxidative stress.

关 键 词：高脂血症 罗布麻叶 网络药理学 分子对接 脂质生物合成 炎症反应调控 氧化应激 

分 类 号：R285.5[医药卫生—中药学]