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山豆根治疗白血病作用机制的网络药理学研究
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| 篇名： | 山豆根治疗白血病作用机制的网络药理学研究 |
| TITLE： | |
| 摘要： | 目的：探讨山豆根治疗白血病的潜在作用机制。方法：运用中药系统药理学分析平台数据库检索山豆根活性成分及其对应靶点蛋白，借助UniProt、PubMed数据库查询活性成分靶点蛋白对应的基因名称，运用Cytoscape 3.6.0软件构建化合物-靶点网络。通过DisGeNET数据库查询与白血病相关的基因（即疾病靶点），借助OmicShare平台筛选山豆根活性成分靶点与白血病疾病靶点的交集基因，利用STRING数据库和Cytoscape 3.6.0软件构建其蛋白-蛋白相互作用（PPI）网络，并进行拓扑学分析；利用DAVID生物信息学数据库进行基因本体（GO）分析和KEGG通路富集分析。结果：共获得山豆根活性成分13个、靶点蛋白204个，节点度值排名靠前的化合物及靶点蛋白包括槲皮素、山柰素以及前列腺素内过氧化物合酶2（PTGS2）、蛋白质丝氨酸蛋白酶1（PRSS1）、钙调蛋白依赖的蛋白激酶（CAMKK2）等。山豆根活性成分靶点与白血病疾病靶点的交集基因共24个，包括IRF1、BCL2、CYP1A1、PIM1等。上述交集基因的PPI网络共包含节点24个、边142条，平均节点度值为6.5，平均介数为0.045。GO分析结果显示，上述交集基因的生物过程涉及缺乏配体的体外凋亡信号通路、凋亡过程的负调控、B细胞增殖的正调控等，分子功能主要包括蛋白质同源化活性、相同蛋白质的结合等，细胞组分主要包括胞外区、线粒体等。KEGG通路富集分析结果显示，上述交集基因主要与T细胞受体信号通路、Janus激酶/信号传导及转录激活因子（JAK/STAT）信号通路、人类嗜T淋巴细胞Ⅰ型病毒（HTLV-Ⅰ）感染等通路有关。结论：山豆根中的活性成分可能通过JAK/STAT信号通路、HTLV-Ⅰ感染等通路作用于PTGS2、PRSS1、CAMKK2等靶点，进而发挥对白血病的治疗作用，呈现多成分、多靶点、多通路的特点。 |
| ABSTRACT： | OBJECTIVE： To investigate the potential mechanism of Sophora tonkinensis in the treatment of leukemia. METHODS： The active components and their target proteins of S. tonkinensis were searched by the analysis of traditional Chinese medicine system pharmacology platform， and UniProt database and PubMed database were used to query corresponding gene names of target proteins of active components. Cytoscape 3.6.0 software was used to construct compound-target network. The genes related to leukemia were searched by DisGeNET databases， and OmicShare platform was used to screen the intersection genes of the active component targets of S. tonkinensis and leukemia disease targets. STRING database and Cytoscape 3.6.0 software were used to construct PPI network， and topological analysis was performed. GO analysis and KEGG pathway enrichment analysis were performed by using DAVID bioinformatics database. RESULTS： There were 13 active components and 204 target proteins in S. tonkinensis. The components and targets with high node degree included quercetin， kaempferol， PTGS2， PRSS1， CAMKK2， etc. There were 24 intersection genes between the active component target and leukemia target， including IRF1， BCL2， CYP1A1， PIM1， etc. PPI network of the above intersection genes contained 24 nodes and 142 edges， with an average node degree of 6.5 and an average medium of 0.045. The results of GO analysis showed that the biological process of the above-mentioned genes involved in apoptosis signaling pathway in vitro without ligands， negative regulation of apoptosis process， positive regulation of B cell proliferation， etc. Molecule function mainly included that protein homology activity and binding of the same protein. Cell components mainly included extracellular region， mitochondria and so on. KEGG pathway enrichment showed that above-mentioned genes were mainly associated with T cell receptor signaling pathway， JAK/STAT signaling pathway， HTLV-Ⅰ infection. CONCLUSIONS： Through JAK/STAT signaling pathway and HTLV-Ⅰ infection pathway， the active components of S. tonkinensis may act on PTGS2， PRSS1， CAMKK2 and other targets， and then play a therapeutic role on leukemia， showing the characteristics of multi-component， multi-target and multi-channel. |
| 期刊： | 2019年第30卷第24期 |
| 作者： | 付海荣，庞毅，谭家华，李晶，邓雪松 |
| AUTHORS： | FU Hairong，PANG Yi，TAN Jiahua，LI Jing，DENG Xuesong |
| 关键字： | 山豆根；白血病；网络药理学；靶点；基因；通路 |
| KEYWORDS： | Sophora tonkinensis； Leukemia； Network pharmacology； Target； Gene； Pathway |
| 阅读数： | 427 次 |
| 本月下载数： | 9 次 |
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