[關鍵詞]
[摘要]
目的 通過網(wǎng)絡藥理學方法探討大黃-桃仁藥對治療肝硬化的潛在作用機制。方法 從中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺(TCMSP)中篩選大黃-桃仁藥對的活性成分,通過蛋白質數(shù)據(jù)庫(Uniprot)獲得各活性成分的潛在靶點,利用TTD、GeneCards、PharmGkb、DrugBank及OMIM數(shù)據(jù)庫獲得肝硬化作用靶點。采用Cytoscape 3.7.2軟件構建大黃-桃仁藥對活性成分-肝硬化-靶點網(wǎng)絡模型,利用String平臺繪制蛋白相互作用(PPI)網(wǎng)絡。通過R studio軟件、Bioconductor軟件等平臺分析篩選出的靶蛋白,獲得基因本體論(gene ontology,GO)富集分析和京都基因與基因組百科全書(Kyoto encyclopedia of genes and genomes,KEGG)富集分析結果,取前30條大黃-桃仁藥對治療肝硬化的信號通路。結果 得到符合條件的大黃-桃仁藥對藥對活性成分29個,β-谷甾醇、常春藤皂苷、蘆薈大黃素與澤蘭黃醇素等為主要有效成分,作用于肝硬化的22個潛在靶點,從PPI網(wǎng)絡得到TP53、MAPK3、HSP90等9個關鍵靶點,富集分析結果發(fā)現(xiàn)大黃-桃仁藥對治療肝硬化的相關生物過程主要包括干預調控血管系統(tǒng)的生成發(fā)育、上皮細胞增殖、脂質代謝、氧化應激等,通過影響癌癥中的microRNAs(miRNAs)表達、PI3K-Akt信號通路、肝細胞癌以及乙型肝炎進程等發(fā)揮治療肝硬化的作用。結論 大黃-桃仁藥對通過調控血管系統(tǒng)生成發(fā)育、上皮細胞增殖、脂質代謝等對肝硬化起到直接或間接的治療作用,其可能作用機制包括癌癥中的miRNAs表達、PI3K-Akt信號通路等。
[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.
[中圖分類號]
R285.5
[基金項目]