基于网络药理学与分子对接探讨“蒲黄-姜黄”抗动脉粥样硬化的作用机制

Anti-atherosclerotic mechanism of Typhae“Pollen-Rhizoma”Curcumae Longae:A study based on network pharmacology and molecular docking

目的:通过网络药理学和分子对接技术对“蒲黄-姜黄”抗动脉粥样硬化的作用机制进行探讨。方法:基于TCMSP数据库获取“蒲黄-姜黄”的有效活性成分及靶点,通过OMIM、GeneCards、DisGeNet、DrugBank数据库挖掘动脉粥样硬化的潜在靶点,将药物与疾病靶点取交集后,利用STRING数据库进行蛋白质蛋白质相互作用(PPI)分析,使用R语言进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析,最后使用PyMOL、AutoDock Vina进行分子对接。结果:共筛选出“蒲黄-姜黄”有效成分9个,与动脉粥样硬化相关靶点190个,核心靶点为转录因子激活蛋白1(JUN)、肿瘤蛋白P53(IP53)、丝裂原激活蛋白激酶1(MAPK1)、苏氨酸蛋白激酶(AKT1)等。GO功能富集分析显示生物过程有2438个、细胞组分有97个、分子功能有252个,共计2787个GO功能条目。KEGG通路富集筛选得到信号通路170条,主要涉及血脂和动脉粥样硬化、流体剪切应力和动脉粥样硬化等。分子对接显示各个成分与靶点均能较好地结合,其中AKT1靶点与这些成分的结合强度最佳。结论:“蒲黄-姜黄”可以多成分、多靶点、多通路地抗动脉粥样硬化。

Objective:To investigate the anti-atherosclerotic mechanism of Typhae“Pollen-Rhizoma”Curcumae Longae based on network pharmacology and molecular docking.Methods:TCMSP database was used to obtain the effective active components and targets of Typhae“Pollen-Rhizoma”Curcumae Longae,and OMIM,GeneCards,DisGeNet,and DrugBank databases were used to obtain the potential targets of atherosclerosis.After the intersecting targets were obtained for drug and disease targets,STRING database was used for protein-protein interaction analysis.R language was used to perform gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and finally PyMOL and AutoDock Vina were used for molecular docking.Results:Related analysis obtained 9 effective components of Typhae“Pollen-Rhizoma”Curcumae Longae and 190 targets associated with atherosclerosis,and the core targets included JUN,TP53,MAPK1,and AKT1.GO functional enrichment analysis obtained 2787 GO terms,among which there were 2438 biological processes,97 cellular components,and 252 molecular functions.KEGG pathway enrichment analysis obtained 170 signaling pathways,which mainly involved blood lipids,atherosclerosis,and fluid shear stress.Molecular docking showed that each component could bind well to the targets,among which AKT1 showed the best binding intensity to these components.Conclusion:Typhae“Pollen-Rhizoma”Curcumae Longae exerts an anti-atherosclerotic effect through multiple components,targets,and pathways.