基于网络药理学和分子对接探讨续断治疗骨质疏松性骨折作用机制  

Discussion on Action Mechanism of Dipsaci Radix for Osteoporotic Fracture Based on Network Pharmacology and Molecular Docking

作　　者：阮家坚 刘金城 蔡东岭[2] 郭伟俊[2] 魏其鹏 向振 董文暄 陈晓峰[2] RUAN Jiajian;LIU Jincheng;CAI Dongling;GUO Weijun;WEI Qipeng;XIANG Zhen;DONG Wenxuan;CHEN Xiaofeng(Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510006,China;The Third Department of Orthopedics,Panyu Hospital of Traditional Chinese Medicine,Guangzhou Guangdong 511400,China)

机构地区：[1]广州中医药大学,广东广州510006 [2]广州市番禺区中医院骨伤三科,广东广州511400

出　　处：《新中医》2024年第5期200-206,共7页New Chinese Medicine

摘　　要：目的:运用网络药理学及分子对接技术探讨续断治疗骨质疏松性骨折(OPF)的作用机制。方法:采用中药系统药理学数据库与分析平台(TCMSP)筛选续断具有高活性的潜在有效成分,通过GeneCards和OMIM数据库筛选OPF的相关靶标,运用Metascape数据库对OPF相关靶标进行映射,确定续断对OPF的可能靶标。利用Cytoscape软件搭建续断治疗OPF的药物-成分-疾病-靶点网络;通过STRING平台构建蛋白质互作网络;利用David数据库提供的续断相关靶标进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析;最后通过分子对接验证核心靶点和续断活性成分的结合能力。结果:续断治疗OPF的主要活性成分主要有龙胆碱(Gentisin)、β-谷甾醇(β-sitosterol)、谷甾醇(Sitosterol)、(E,E)-3,5-二邻咖啡酰奎宁酸[(E,E)-3,5-Di-O-caffeoylquinic acid]和林生续断苷Ⅲ-qt(SylvestrosideⅢ-qt)等成分,其作用于半胱氨酸天冬氨酸蛋白酶3 (CASP3)、β2-肾上腺素受体基因(ADRB2)、Bcl-2相关X蛋白(BAX)、B淋巴细胞瘤-2基因(BCL2)、半胱氨酸天冬氨酸蛋白酶8 (CASP8)、雌激素受体2 (ESR2)、半胱氨酸天冬氨酸蛋白酶9 (CASP9)、二肽基肽酶-4 (DPP4)、糖原合成酶激酶3 (GSK3β)、异常凝血酶原(F2)等靶点。续断能够通过参与转录调控和细胞凋亡执行阶段的半胱氨酸型内肽酶、G蛋白偶联胺受体、缩氨酸酶活性等生物过程,调控癌症通路、弓形体病、卡波西肉瘤相关的疱疹病毒感染、乙型肝炎、大肠癌、小细胞肺癌脂质与动脉粥样硬化、雌激素信号通路来发挥治疗OPF的作用。分子对接结果显示,续断的活性成分(E,E)-3,5-二邻咖啡酰奎宁酸、龙胆碱、威岩仙皂苷A_qt、β-谷甾醇与CASP3、ADRB2、CASP8有较好的亲和力。结论:续断可通过直接作用骨代谢相关途径和参与调节上下游多个信号通路对OPF进行治疗,CASP3及癌症通路可能是其治疗OPF的关键靶点及通路�Objective:To explore the action mechanism of Dipsaci Radix for osteoporotic fracture(OPF)based on network pharmacology and molecular docking.Methods:The potential active components of Radix Dipsaci with high activity were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP);the related targets of OPF were screened by GeneCards and OMIM database;the potential targets of Dipsaci Radix against OPF were identified by phase mapping of the related targets of OPF by Metascape database.The"medicines-compositions-diseases-targets"network of Dipsaci Radix for OPF was constructed by Cytoscape software;the protein-protein interaction network was constructed by STRING platform;the genetic ontological(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by the Dipsaci Radix-related targets provided by the David database.Finally,the binding ability of the core targets and the active ingredients of Dipsaci Radix was verified by molecular docking.Results:The main active ingredients of Dipsaci Radix for OPF mainly include Gentisin,β-sitosterol,Sitosterol,(E,E)-3,5-Di-O-caffeoylquinic acid and Sylvestroside II-qt,which act on caspase 3(CASP3),β2-adrenergic receptor gene(ADRB2),Bcl-2 associated X protein(BAX),B lymphocytoma-2 gene(BCL2),caspase 8(CASP8),estrogen receptor 2(ESR2),caspase 9(CASP9),dipeptidyl peptidase-4(DPP4),glycogen synthase kinase 3(GSK3β),abnormal prothrombin(F2)and other targets.By participating in biological processes such as cysteine endopeptidase,G protein-coupled amine receptor,and peptidase activity in the executive phase of transcriptional regulation and apoptosis,Dipsaci Radix regulated cancer pathways and signaling pathways of toxoplasmosis,Kaposi sarcoma-associated herpesvirus infection,hepatitis B,colorectal cancer,lipids of small cell lung cancer,atherosclerosis,and estrogen to treat OPF.Molecular docking results showed that the active ingredients of Dipsaci Radix(E,E)-3,5-Di-O-caffeoylquinic acid,Gentianine,Cau

关 键 词：骨质疏松性骨折 续断 网络药理学 分子机制 分子对接 

分 类 号：R683[医药卫生—骨科学]