[关键词]
[摘要]
目的 通过网络药理学方法探讨大黄-桃仁药对治疗肝硬化的潜在作用机制。方法 从中药系统药理学数据库与分析平台(TCMSP)中筛选大黄-桃仁药对的活性成分,通过蛋白质数据库(Uniprot)获得各活性成分的潜在靶点,利用TTD、GeneCards、PharmGkb、DrugBank及OMIM数据库获得肝硬化作用靶点。采用Cytoscape 3.7.2软件构建大黄-桃仁药对活性成分-肝硬化-靶点网络模型,利用String平台绘制蛋白相互作用(PPI)网络。通过R studio软件、Bioconductor软件等平台分析筛选出的靶蛋白,获得基因本体论(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析结果,取前30条大黄-桃仁药对治疗肝硬化的信号通路。结果 得到符合条件的大黄-桃仁药对药对活性成分29个,β-谷甾醇、常春藤皂苷、芦荟大黄素与泽兰黄醇素等为主要有效成分,作用于肝硬化的22个潜在靶点,从PPI网络得到TP53、MAPK3、HSP90等9个关键靶点,富集分析结果发现大黄-桃仁药对治疗肝硬化的相关生物过程主要包括干预调控血管系统的生成发育、上皮细胞增殖、脂质代谢、氧化应激等,通过影响癌症中的microRNAs(miRNAs)表达、PI3K-Akt信号通路、肝细胞癌以及乙型肝炎进程等发挥治疗肝硬化的作用。结论 大黄-桃仁药对通过调控血管系统生成发育、上皮细胞增殖、脂质代谢等对肝硬化起到直接或间接的治疗作用,其可能作用机制包括癌症中的miRNAs表达、PI3K-Akt信号通路等。
[Key word]
[Abstract]
Objective To explore the potential mechanism of Rhei Radix et Rhizoma-Persicae Semen in treatment of liver cirrhosis by network pharmacology. Methods With the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), the effective chemical components and target genes of Rhei Radix et Rhizoma-Persicae Semen were filtrated. Potential targets of active components were obtained through the Protein Database (UNIPROT). According to the TTD、GeneCard、PharmGkb、DrugBank and OMIM Databases, targets of liver cirrhosis were collected. The Cytoscape 3.7.2 software was used to construct the Rhei Radix et Rhizoma-Persicae Semen active components-liver cirrhosis-targets network. String platform was used to construct a protein-protein interaction (PPI) network. Gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways analysed of screened target proteins were employed by R and Bioconductor software, and the top 30 of them were selected. Results A total of 29 bioactive components of Rhei Radix et Rhizoma-Persicae Semen could act on 22 potential targets of liver cirrhosis. Nine key therapeutic targets were collected such as TP53、MAPK3、HSP90 by the constructed PPI network. The enrichment analysis showed that the Rhei Radix et Rhizoma-Persicae Semen treatments for liver cirrhosis signal pathways including regulation of vasculature development and angiogenesis, epithelial cell proliferation, lipid metabolic process,response to oxygen levels and so on. Rhei Radix et Rhizoma-Persicae Semen anti-liver cirrhosis by changing biological related process such as microRNAs (miRNAs) in cancer, PI3K-Akt signaling pathway, hepatocellular carcinoma, hepatitis B. Conclusion Rhei Radix et Rhizoma-Persicae Semen had direct or indirect therapeutic effects on liver cirrhosis through regulating vasculature and angiogenesis, epithelial cell proliferation, regulation of lipid metabolic process and so on. The possible potential signal pathways including miRNAs in cancer, PI3K-Akt signaling pathway and so on.
[中图分类号]
R285.5
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