基于网络药理学及分子对接的新疆红花防龋作用机制研究  

Study on Mechanism of Caries Prevention of Xinjiang Safflower Based on Network Pharmacology and Molecular Docking

作　　者：李新尚[1] 连冰洁[2] 牛巧丽[2] LI Xinshang;LIAN Bingjie;NIU Qiaoli(Department of General and Emergency Dentistry,the First Affiliated Hospital of Xinjiang Medical University(Affiliated Stomatology Hospital),Urumqi 830054,China;Department of Endodontics,the First Affiliated Hospital of Xinjiang Medical University(Affiliated Stomatology Hospital),Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院(附属口腔医院)口腔急诊综合科,乌鲁木齐830054 [2]新疆医科大学第一附属医院(附属口腔医院)牙体牙髓科,乌鲁木齐830054

出　　处：《医学综述》2023年第23期5489-5496,共8页Medical Recapitulate

基　　金：中华口腔医学会西部口腔医学临床科研基金项目(CSA-W2021-02)。

摘　　要：目的通过网络药理学和分子对接探讨新疆红花防龋的活性成分、潜在靶点及其作用机制。方法通过TCMSP和BATMAN-TCM在线免费数据库按照ADME(吸收、分布、代谢和排泄)参数和Lipinski规则(分子量<500、脂水分配系数<5、氢键供体<5、氢键受体<10)筛选红花活性成分,并用TCMSP和Uniprot数据库筛选活性成分对应的靶点。利用CTD、GeneCards和DisGeNET等数据库检索获取龋病的靶点,并与红花活性成分靶点进行映射,共有靶点作为红花防龋的潜在靶点。针对潜在靶点用Cytoscape 3.8.2软件构建网络,利用DAVID数据库的在线分析功能基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,采用String数据库、Cytoscape软件CytoNCA和MCODE插件分析蛋白互相作用,将作用强的靶点作为红花防治龋病的关键靶点。基于TCMSP数据库和PyMol软件预处理红花活性成分,准备配体。采用PDB数据库和PyMol软件预处理关键靶点,准备受体。用AutoDock 1.4软件分子对接。结果从红花中筛选得到木脂素和红花素等56个活性成分及其181个作用靶点,与2486个龋病靶点交集得到81个潜在靶点。GO和KEGG分析中潜在靶点涉及367条生物学过程、72条分子功能、52条细胞组成以及113条信号通路。红花黄芩素、山柰酚等活性成分与肿瘤坏死因子(TNF)、RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)具有较好的结合活性。结论红花的木脂素和红花素等成分可能通过作用于AKT1、TP53、TNF和促分裂原活化的蛋白激酶1等靶点调节TNF信号通路,从而发挥防龋作用。Objective To explore the active components,potential targets and mechanisms of action of Xinjiang safflower against caries by network pharmacology and molecular docking.Methods Safflower active ingredients were screened according to ADME(absorption,distribution,metabolism and excretion)parameters and Lipinski′s rule(MW<500,AlogP<5,Hdon<5,Hacc<10)by TCMSP and BATMAN-TCM online free databases,and targets corresponding to active ingredients were screened by TCMSP and Uniprot databases.Caries targets were obtained by searching with CTD,GeneCards and DisGeNET databases and mapped with the targets of safflower active ingredients,and the common targets were used as potential targets of safflower against caries.Cytoscape 3.8.2 software was used to construct a network for potential targets,utilizing the online analysis function of the DAVID database,gene ontology(GO),and Kyoto encyclopedia of genes and genomes(KEGG)for enrichment analysis,using String database,Cytoscape software,CytoNCA,and MCODE plugins to analyze protein interactions,and the powerful targets were identified as key targets for safflower caries prevention and treatment.Based on TCMSP database and PyMol software,the active ingredients of safflower were pretreated to prepare the ligands.The key target points were pre-processed based on PDB database and PyMol software to prepare the receptors.Molecular docking was performed with AutoDock 1.4 software.Results Fifty-six active ingredients including lignan and carthamidin and their 181 targets of action were screened from safflower and intersected with 2486 caries targets to obtain 81 potential targets.367 biological processes,72 molecular functions,52 cellular components,and 113 signaling pathways were involved in the potential targets in GO and KEGG analysis.The active components of safflower baicalein and kaempferol had good binding activities with tumor necrosis factor(TNF)and RAC-αserine/threonine protein kinase(AKT1).Conclusion Lignan and carthamidin components of safflower may regulate the TNF signali

关 键 词：龋病 红花 分子对接 网络药理学 作用机制 

分 类 号：R285.5[医药卫生—中药学]