三七治疗骨关节炎机制:基于UHPLC-QE-MS、网络药理学及分子动力学模拟  

Based on UHPLC-QE-MS,network pharmacology,and molecular dynamics simulation to explore the mechanism of Panax notoginseng in treating osteoarthritis

作　　者：陈跃平[1] 陈锋[2] 彭清林 陈荟伊 董盼锋[1] Chen Yueping;Chen Feng;Peng Qinglin;Chen Huiyi;Dong Panfeng(Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,Guangxi Zhuang Autonomous Region,China;Guangxi University of Chinese Medicine,Nanning 530200,Guangxi Zhuang Autonomous Region,China;Harbin Medical University,Harbin 150086,Heilongjiang Province,China)

机构地区：[1]广西中医药大学附属瑞康医院,广西壮族自治区南宁市530011 [2]广西中医药大学,广西壮族自治区南宁市530200 [3]哈尔滨医科大学,黑龙江省哈尔滨市150086

出　　处：《中国组织工程研究》2025年第8期1751-1760,共10页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(82360937),项目参与人:董盼锋;广西壮族自治区临床重点专科(创伤外科)建设项目(部门预算社(2023)1号),项目负责人:陈跃平;广西中医药适宜技术开发与推广项目(GZSY22-36),项目参与人:陈跃平;广西中医药大学A类“桂派中医药传承创新团队”项目(2022A004),项目负责人:陈跃平。

摘　　要：背景:课题组前期研究发现三七能够修复骨细胞的形态结构,对于治疗骨关节炎具有良好的应用前景,但目前对于三七的具体作用机制尚不清楚。目的:采用超高效液相色谱-四极杆-静电场轨道阱串联质谱(ultra-high performance liquid chromatography-Q exactive-mass spectrometry,UHPLC-QE-MS)技术鉴定三七的主要成分,并结合网络药理学、分子对接和分子动力学模拟探究三七治疗骨关节炎的作用机制。方法:利用UHPLC-QE-MS技术鉴定三七的主要成分后,运用TCMSP数据库筛选活性成分,通过TCMSP和Uniprot数据库查找活性成分靶点,通过疾病数据库筛选骨关节炎靶点。在药物靶点与疾病靶点取交集后,导入STRING数据库和Cytoscape软件构建蛋白互作网络筛选关键靶点,通过“活性成分-作用靶点”网络筛选关键活性成分。再对关键靶点进行富集分析,并对关键活性成分和关键靶点进行分子对接验证,最后选取结合能最低的结果进行分子动力学模拟。结果与结论:①在三七溶液中共鉴定出57种活性成分,成分靶点与疾病靶点交集50个,关键活性成分5个(槲皮素、熊脱氧胆酸、山奈酚、柚皮素和红藻氨酸),关键靶点5个(白细胞介素6、基质金属蛋白酶9、白细胞介素1β、白蛋白和趋化因子配体2);②基因本体功能富集642个条目,其中620个条目代表生物过程,21个条目代表分子功能,1个条目代表细胞成分;京都基因与基因组百科全书通路分析63条通路,主要涉及雌激素信号通路、白细胞介素17信号通路和高糖基化终末产物-高糖基化终末产物受体信号通路;③分子对接显示关键活性成分和关键靶点结合活性良好,分子动力学模拟提示槲皮素和基质金属蛋白酶9间的相互作用稳定;④对三七成分进行了较全面研究,初步阐明了其药效物质基础,预测三七可通过多组分、多靶点、多途径和多通路发挥抗炎、软骨保护和免疫调�BACKGROUND:Our previous research found that Panax notoginseng can repair the morphological structure of bone cells,which has a good application prospect in the treatment of osteoarthritis,but the specific mechanism of Panax notoginseng is still unclear.OBJECTIVE:To identify the main components of Panax notoginseng using ultra-high performance liquid chromatography-Q exactive-mass spectrometry(UHPLC-QE-MS),and to explore the mechanism of Panax notoginseng in the treatment of osteoarthritis by combining network pharmacology,molecular docking and molecular dynamics simulation.METHODS:After identifying the main components of Panax notoginseng by UHPLC-QE-MS technology,the active components were screened by TCMSP database,and the targets of active components were found by TCMSP and Uniprot database.Osteoarthritis targets were screened out through disease databases.After the intersection of drug targets and disease targets,the protein-protein interaction network was constructed by importing STRING database and Cytoscape software,and the“active ingredient-action target”network was constructed to screen key active ingredients.Then the key targets were enriched and analyzed,and the key active components and key targets were verified by molecular docking.Finally,the results with the lowest binding energy were selected for molecular dynamics simulation.RESULTS AND CONCLUSION:A total of 57 active components were identified in the solution of Panax Notoginseng,including 50 intersection targets of components and disease targets,5 key active components(quercetin,ursodeoxycholic acid,kaempferol,naringenin and erythrocyanine),and 5 key targets(interleukin 6,matrix metalloproteinase 9,interleukin 1β,albumin and recombinant chemokine c-motif ligand 2).Gene ontology enriched 642 entries,among which 620 entries represent biological processes,21 entries represent molecular functions,and 1 entry represents cellular components.Kyoto encyclopedia of genes and genomes analysis indicated 63 pathways,mainly including estrogen signaling

关 键 词：三七 骨关节炎 分子动力学模拟 质谱 分子对接 网络药理学 

分 类 号：R453.9[医药卫生—治疗学] R313[医药卫生—临床医学] R274.9