基于网络药理学和分子对接探讨娑罗子治疗脑水肿的作用机制  

Mechanism of action of Semen Aesculi in treatment of cerebral edema:A study based on network pharmacology and molecular docking

作　　者：段妍琴[1] 刘胜兰 刘海姣 彭颖 黄建华 刘东亮[3] DUAN Yanqin;LIU Shenglan;LIU Haijiao;PENG Ying;HUANG Jianhua;LIU Dongliang(The Fourth Hospital of Changsha/Changsha Hospital of Hunan Normal University,Changsha 410006,Hunan,China;Institute of Herbal Cuisine and Diet Therapy,Hunan Academy of Chinese Medicine,Changsha 410006,Hunan,China;Institute of Basic Traditional Chinese Medicine Research,Hunan Academy of Chinese Medicine,Changsha 410006,Hunan,China)

机构地区：[1]长沙市第四医院/湖南师范大学附属长沙医院,湖南长沙410006 [2]湖南省中医药研究院药膳食疗研究所,湖南长沙410006 [3]湖南省中医药研究院中医基础研究所,湖南长沙410006

出　　处：《湖南中医杂志》2023年第8期158-165,共8页Hunan Journal of Traditional Chinese Medicine

基　　金：湖南省长沙市自然科学基金项目(kq2202028)。

摘　　要：目的:运用网络药理学和分子对接技术分析探讨中药娑罗子治疗脑水肿的潜在靶点及作用机制。方法:基于HERB数据库收集娑罗子化学成分及其靶标基因;通过OMIM、GeneCards、Drug Bank等数据库获取脑水肿疾病靶标基因;将成分靶标、疾病靶标交集部分上传至STRING数据库,构建中药成分靶标-疾病靶标蛋白质-蛋白质相互作用(PPI)网络,并计算网络特征值,筛选出关键靶标。借助Metascape分析平台对关键靶标进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,并使用AutoDock软件进行分子对接验证。结果:共获取娑罗子有效活性成分24个,治疗脑水肿交集靶标108个,GO功能富集分析得到2634条生物过程(BP)条目、183条分子功能(MF)条目、72条细胞组分(CC)条目。KEGG通路富集分析结果显示,娑罗子治疗脑水肿涉及的通路包括癌症通路、脂质动脉粥样硬化、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、血管内皮生长因子(VEGF)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路等。分子对接结果验证了有效成分和关键靶点的相互作用,其中七叶皂苷苷元A、七叶皂苷苷元C与脑水肿相关通路的关键蛋白有较强的对接活性。结论:中药娑罗子治疗脑水肿的效应机制可能与炎症反应、抗氧化应激等相关。Objective:To investigate the potential targets and mechanism of action of Semen Aesculi in the treatment of cerebral edema based on network pharmacology and molecular docking.Methods:HERB database was used to obtain the chemical components of Semen Aesculi and their target genes;databases such as OMIM,Gene-Cards,and Drug Bank were used to obtain the disease targets of encephaledema;the intersection of the above two groups of targets were obtained and uploaded to STRING database to construct a protein-protein interaction(PPI)network for the targets of components and disease targets,and network characteristic values were calculated to identify key targets.Metascape platform was used to perform the gene ontology(GO)functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of key targets,and AutoDock software was used to perform molecular docking validation.Results:The above analyses obtained 24 active components of Semen Aesculi and 108 intersecting targets in the treatment of cerebral edema.The GO functional enrichment analysis obtained 2634 biological process(BP)terms,183 molecular function(MF)terms,and 72 cellular component(CC)terms,and the KEGG pathway enrichment analysis showed that the pathways involved in the treatment of cerebral edema by Semen Aesculi included the cancer pathway,lipids and atherosclerosis,the PI3K/Akt signaling pathway,the VEGF signaling pathway,and the MAPK signaling pathway.The results of molecular docking validated the interaction between the effective constituents and the key targets,among which aescinate A and aescinate C showed relatively strong binding activity to the key proteins in the pathways associated with cerebral edema.Conclusion:The effect mechanism of the traditional Chinese medicine Semen Aesculi in the treatment of cerebral edema may be associated with inflammatory response and anti-oxidative stress effect.

关 键 词：脑水肿 娑罗子 网络药理学 分子对接 作用机制 

分 类 号：R277.72[医药卫生—中医学]