基于网络药理学与分子对接探讨岭南药材三桠苦茎叶治疗类风湿性关节炎的作用特点  

Exploration on Action Characteristics of the Stems and Leaves of Melicope ptelefolia on the Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

作　　者：陈永安 黄雅阳 苏安宇 莫静媛 冯雯敏 廖卫国[1] 朱盛华[3] 王利胜[1] CHEN Yong'an;HUANG Yayang;SU Anyu;MO Jingyuan;FENG Wenmin;LIAO Weiguo;ZHU Shenghua;WANG Lisheng(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;School of Pharmacy,Guangzhou Medical University,Guangzhou 510000 Guangdong,China;School of Pharmacy,Guangdong Food and Drug Vocational College,Guangzhou 510520 Guangdong,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006 [2]广州医科大学药学院,广东广州510000 [3]广东食品药品职业学院药学院,广东广州510520

出　　处：《中药新药与临床药理》2023年第8期1105-1116,共12页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省中医药局科研项目(20231245);广州市科技计划项目(202206010188);广州中医药大学“双一流”与高水平大学学科协同创新团队培育项目(2021xk78)。

摘　　要：目的采用网络药理学与分子对接技术对三桠苦茎与叶治疗类风湿性关节炎的作用特点进行研究与比较。方法通过PubMed与中国知网收集三桠苦茎和叶的化学成分信息并于SwissADME平台进行成分筛选,使用Swiss Target Prediction平台进行靶点预测;利用DrugBank、GeneCards和OMIM数据库检索与类风湿性关节炎相关的疾病靶点并与三桠苦茎和叶的活性成分作用靶点进行映射取交集,通过Cytoscape软件构建“活性成分-有效靶点”网络;将共同靶点导入STRING数据库构建蛋白互作网络;应用Metascape数据库进行GO功能及KEGG通路富集分析;采用CB-DOCK2进行关键成分与有效靶点的分子对接研究。结果三桠苦茎中筛选得54个活性成分,与类风湿性关节炎交集靶点40个;三桠苦叶中筛选得91个活性成分,与类风湿性关节炎交集靶点102个;在三桠苦茎与叶度值大于二倍中位数的活性化合物群中,不存在共有活性成分;三桠苦茎与叶治疗类风湿性关节炎的核心靶点与关键通路出现交叉并在生物过程中呈现出多向协同作用;预测三桠苦茎干预RA的核心成分4-甲基喹诺酮、藿香黄酮醇、亚油酸等与叶干预RA的核心成分山柰酚、槲皮素、异鼠李素可能通过AKT1、EGFR与MCL1等共同靶点,作用于PPAR、类固醇激素生物合成与NF-κB等共同信号通路干预RA;在分子对接验证中,所有结合能均小于-5 kcal·mol^(-1),其中三桠苦茎中结合能小于-7 kcal·mol^(-1)的有11组,叶中有19组,分别占44%和63%。结论三桠苦茎与叶干预RA的活性成分具有明显差异但作用机制高度协同;三桠苦叶在RA的干预中可能展现出比茎更强的活性。本研究为进一步开展三桠苦入药部位研究及临床应用提供了理论基础。Objective To study and compare the action characteristics of the stems and leaves of Melicope ptelefolia on the treatment of rheumatoid arthritis(RA)based on network pharmacology and molecular docking.Methods The ingredients of the stems and leaves of Melicope ptelefolia was collected from PubMed and CNKI.Subsequently,the active ingredients were screened through SwissADME database,and the targets were predicted through Swiss Target Prediction platform.The RA-related targets were retrieved using DrugBank,GeneCards and OMIM databases,and then the RA-related targets were intersected with the active ingredient targets from the stems and leaves of Melicope ptelefolia for RA.The“active ingredients-key target”network was constructed through the Cytoscape software.The common targets were imported into STRING database to construct a protein-protein interaction network.The Metascape database was used for GO function and KEGG pathway enrichment analysis;the molecular docking research between the key ingredients and the targets of Melicope ptelefolia was conducted using CB-DOCK2.Results A total of 54 active ingredients and 40 targets were screened from the stems of Melicope ptelefolia;91 active ingredients and 102 targets were screened from the leaves of Melicope ptelefolia.There were no common ingredients in the groups of active compounds from stems and leaves with the degree values greater than double the median.The intersection between core targets and key pathways of the stems and leaves from Melicope ptelefolia for treating RA was found and exhibited multidirectional synergy in biological process.Melicope ptelefolia may act on the core targets of AKT1,EGFR and MCL1through 4-methylquinolin-2-ol,pachypodol,linoleic acid and other major active ingredients in stems and kaempferol,quercetin,isorhamnetin and other major active ingredients in leaves,and synergistically exert therapeutic effects on RA through PPAR,steroid hormone biosynthesis,NF-κB and other signaling pathways.The binding energies were less than-5 kcal·mo

关 键 词：三桠苦 类风湿性关节炎 入药部位 物质基础 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]