酸枣仁抗动脉粥样硬化的分子靶点及作用机制研究

Discussion about the molecular targets and mechanism of Ziziphus jujuba in anti-atherosclerosis

目的结合网络药理学和分子对接方法分析酸枣仁抗动脉粥样硬化(AS)的有效成分、分子靶点及作用机制。方法通过TCMSP数据库检索酸枣仁有效成分及作用靶点,利用GeneCards、OMIM、TTD、pharmgKB、DrugBank及DisGeNET等数据库筛选AS疾病相关靶点,取两者交集靶点进行蛋白互作网络(PPI)分析,获取关键靶点后进行通路富集分析,构建“酸枣仁有效成分—核心靶点—通路”网络。利用分子对接对酸枣仁核心有效成分与靶点进行验证。结果共获得酸枣仁有效成分9个,核心靶点268个,GO功能分析得到生物途径2180条,KEGG分析得到信号通路159条,其中与AS相关的信号通路主要有PI3K/AKT、脂质和动脉粥样硬化、MAPK等。分子对接结果显示,酸枣仁皂苷A、齐墩果碱、酸枣仁环肽等有效成分与核心靶点MAPK1、MAPK3、PIK3CA、PIK3CB、AKT1存在较强的结合能力。结论酸枣仁可能通过酸枣仁皂苷A、齐墩果碱、酸枣仁环肽等有效成分,作用于MAPK1、MAPK3、PIK3CA、PIK3CB、AKT1等分子靶点,进而调控PI3K/AKT、脂质与动脉粥样硬化、MAPK等作用通路发挥抗AS的作用。

Objective To analyze the active components,molecular targets,and mechanism of anti-atherosclerosis(AS)of Ziziphus jujuba by network pharmacology and molecular docking methods.Methods The active components of Ziziphus jujuba and their targets were identified by TCMSP database.Disease-related targets of AS were obtained from GeneCards,OMIM,TTD,pharmgKB,DrugBank and DisGeNET databases.The PPI network analysis was conducted by intersecting the two sets of targets to identify the key targets.Pathway enrichment analysis was performed to construct a network representing the"active components-core target-signal pathway"of Ziziphus jujuba.Finally,the core effective components and their targets were verified by molecular docking.Results A total of 9 active components and 268 common pharmacological targets were identified.GO analysis yielded 2180 biological pathways,while KEGG analysis identified 159 signaling pathways.Among these,the AS-related pathways mainly involved PI3K/AKT,lipid and atherosclerosis,MAPK and so on.Molecular docking results demonstrated strong binding ability of active components such as Jujuboside A,Zizyphusine and Sanjoinenine with core targets including MAPK1,MAPK3,PIK3CA,PIK3CB,and AKT1.Conclusion Ziziphus jujuba may play a role in the treatment of AS by acting on the molecular targets,including MAPK1,MAPK3,PIK3CA,PIK3CB,and AKT1,through active components such as Jujuboside A,Zizyphusine,and Sanjoinenine.Furthermore,this regulation influences agains AS related pathways associated with PI3K/AKT,lipids and atherosclerosis,MAPK,and so on.