基于网络药理学及分子对接技术探讨绞股蓝治疗代谢相关脂肪性肝病的作用机制

Mechanism of Gynostemma pentaphyllum in treatment of metabolism associated fatty liver disease based on network pharmacology and molecular docking

运用网络药理学及分子对接技术探究绞股蓝治疗代谢相关脂肪性肝病(metabolic associated fatty liver disease, MAFLD)的作用机制。利用TCMSP数据库收集绞股蓝的主要活性成分及作用靶点,通过GeneCards、OMIM、TTD数据库获取疾病相关靶点,并筛选出3个数据库交集靶点后,在UniProt数据库转换为标准基因名称,经Venn工具获取药物-疾病交集靶点基因,将交集靶点基因上传至STRING数据库构建蛋白相互作用网络,并利用Cytoscape软件进行"药物-活性成分-共同靶点-疾病"网络的构建与分析。借助DAVID数据库对交集靶点进行基因本体(gene ontology, GO)分析和基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)信号通路富集分析。运用Pymol软件对药物活性成分与共同靶点进行分子对接和结合能力预测。结果共筛选出绞股蓝皂苷、槲皮素、谷甾醇等绞股蓝有效活性成分24个,包括作用靶点92个,与代谢相关脂肪性肝病共同靶点54个,关键靶点包括TNF、IL6、PTGS2、TP53、CCL2、VEGFA等。分析GO生物过程、分子功能、细胞组分及KEGG通路相关条目,主要涉及NF-κB、PI3K-Akt、TNF及HIF-1等信号通路。分子对接结果显示,绞股蓝皂苷、槲皮素与TNF、IL6、PTGS2具有强烈的结合能力。该研究发现绞股蓝可能从抗炎、抗氧化应激、改善胰岛素抵抗等多方面发挥对代谢相关脂肪性肝病的治疗作用,为绞股蓝抗代谢相关脂肪性肝病的开发和应用提供思路和理论依据。

The present study explored the mechanism of action of Gynostemma pentaphyllum in the treatment of metabolism associa-ted fatty liver disease(MAFLD) by network pharmacology and molecular docking. The main active components and action targets of G. pentaphyllum were collected from TCMSP. Disease-related targets were obtained from GeneCards, OMIM and TTD, and the common targets of the three databases were screened out, which were converted to the genes with standard names by UniProt. The drug-disease common target genes were obtained through Venn tool and uploaded to STRING for the construction of the protein-protein interaction(PPI) network. Cytoscape was used to construct and analyze the drug-active component-common target-disease network. The gene ontology(GO) analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed on the common targets by DAVID. Pymol was adopted to perform molecular docking of active components and the common targets and predict their binding ability. Twenty-four active components(such as gypenosides, quercetin and sitosterol) of G. pentaphyllum were screened out. Ninety-two targets were obtained and 54 common targets were identified. Key targets included TNF, IL6, PTGS2, TP53, CCL2 and VEGFA. GO analysis on biological processes, molecular functions and cellular components and KEGG pathway analysis were performed, and the results indicated that NF-κB, PI3 K-Akt, TNF and HIF-1 signaling pathways were mainly involved. Molecular docking results showed that gypenosides and quercetin had a strong binding ability to TNF, IL6 and PTGS2. The findings of this study revealed that the therapeutic efficacy of G. pentaphyllum on MAFLD might be achieved by resisting inflammation and oxidative stress and improving insulin resistance, providing ideas and a theoretical basis for the development and application of G. pentaphyllum in the treatment of MAFLD.