| 摘要: |
| 目的：本研究通过系统药理学方法探讨古汉养生精治疗癫痫的靶点、通路及有效成分。方法：利用TCMSP数据库筛选出古汉养生精中治疗癫痫的有效成分和相关靶标蛋白，运用Cytoscape 3.6.0软件构建古汉养生精有效成分-靶标可视化相互作用网络并进行网络拓扑学分析，同时利用蛋白质-蛋白质相互作用（PPI）进行网络构建与分析。从UniProt数据库中获取靶标蛋白的基因名称后，借助David数据库进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。基于上述方法研究古汉养生精治疗癫痫的作用机制。结果：发现古汉养生精药方含有1 258种化学成分，经筛选后选取活性化合物共166种，去重后共126种。从TCMSP数据库中检索到这些活性成分的潜在蛋白质靶标为172个，112个蛋白质靶点被发现与癫痫有关。PPI网络图显示信号传导和转录激活因子3（STAT3）、转录因子AP-1的亚基c-Jun（JUN）、蛋白激酶B1（AKT1）、丝裂原活化蛋白激酶1（MAPK1）、丝裂原活化蛋白激酶3（MAPK3）等Degree较其他蛋白节点高，说明这些蛋白质在网络中起着关键作用。GO功能富集分析显示，古汉养生精主要与核受体活性、辅因子结合、神经递质活性等生物功能有关。KEGG通路富集分析结果表明，古汉养生精的关键靶点基因富集与肿瘤坏死因子（TNF）信号传导通路和缺氧诱导因子-1（HIF-1）信号传导通路等氧化应激及炎症相关信号通路有关。结论：古汉养生精有多种成分并且是通过多种途径作用于多种靶点发挥其药物功效。STAT3、JUN、 AKT1、MAPK1、MAPK3、淀粉样前体蛋白（APP）、转录激活因子p65（RELA）、白细胞介素-6（IL-6）、丝裂原活化蛋白激酶8（MAPK8）等可能是古汉养生精在癫痫治疗中的重要调节因子。此外，神经炎症和氧化应激可能在古汉养生精治疗癫痫中起重要作用。 |
| 关键词: 癫痫 古汉养生精 系统药理学 有效成分 靶点 通路 |
| DOI： |
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| Prediction of effective constituents in Ancient Han Health-Keeping Extract in treatment of epilepsy and related targets and pathways |
| YUAN Xingxing,SHUAI Niannian,ZHOU Jiaxiu |
| (Hunan Provincial People’s Hospital，Changsha 410002，Hunan，China;Shenzhen Second People’s Hospital，Shenzhen 518000，Guangdong，China) |
| Abstract: |
| Objective：To investigate the targets，pathways，and effective constituents of Ancient Han Health-Keeping Extract in the treatment of epilepsy based on systems pharmacology.Methods：TCMSP database was used to obtain the effective constituents of Ancient Han Health-Keeping Extract in the treatment of epilepsy and related targeted proteins，and Cytoscape 3.6.0 was used to establish a visualized effective constituent-target interaction network and perform the network topology analysis.A protein-protein interaction (PPI) network was established and analyzed.UniProt database was used to obtain the gene names of target proteins，and DAVID database was used to perform the gene ontology (GO) functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.The above methods were used to investigate the mechanism of action of Ancient Han Health-Keeping Extract in the treatment of epilepsy.Results：A total of 1 258 chemical components were identified for Ancient Han Health-Keeping Extract，and 166 active compounds were identified after screening，with 126 compounds after duplication elimination.A total of 172 potential protein targets were obtained for these active components in TCMSP database，among which 112 protein targets were found to be associated with epilepsy.The PPI network showed that STAT3，JUN，AKT1，MAPK1，and MAPK3 had higher degree values than the other protein nodes，suggesting that these proteins played a key role in the network.The GO functional enrichment analysis showed that Ancient Han Health-Keeping Extract was mainly associated with the biological functions such as nuclear receptor activity，cofactor binding，and neurotransmitter activity.The KEGG pathway enrichment analysis showed that the key targets of Ancient Han Health-Keeping Extract were associated with the oxidative stress and inflammation signaling pathways such as the TNF signal transduction pathway and the HIF-1 signal transduction pathway.Conclusion：Ancient Han Health-Keeping Extract has multiple components and exerts a therapeutic effect by acting on various targets through multiple pathways.STAT3，JUN，AKT1，MAPK1，MAPK3，APP，RELA，IL-6，and MAPK8 might be important regulatory factors for Ancient Han Health-Keeping Extract in the treatment of epilepsy.In addition，neuroinflammation and oxidative stress may play an important role in the treatment of epilepsy by Ancient Han Health-Keeping Extract. |
| Key words: epilepsy Ancient Han Health-Keeping Extract systems pharmacology effective constituents target pathway |
