PDF(Pubmed)
Abstract：
Taraxacum mongolicum (TM) is a widely used herb. Studies have reported that TM exhibits growth-inhibitory and apoptosis-inducing on multiple tumors, including hepatocellular carcinoma (HCC). The active ingredients, targets, and molecular mechanisms of TM against HCC need to be further elucidated.
We identified the active ingredients and targets of TM via HERB, PubChem, SwissADME, SwissTargetPrediction, and PharmMapper. We searched HCC targets from GeneCards, Comparative Toxicogenomics Database (CTD), and DisGeNET. Then, the intersection of drug targets and disease targets was uploaded to the STRING database to construct protein-protein interactions (PPI) networking whose topology parameters were analyzed in Cytoscape software to screen hub targets. Next, we used Metascape for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and we employed AutoDock vina, AMBER18 and PyMOL software along with several auxiliary tools for molecular docking and molecular dynamics (MD) simulation. Finally, based on the in silico findings, cellular experiments were conducted to investigate the effect of TM on HSP90AA1 gene expression.
A total of 228 targets and 35 active ingredients were identified. Twenty two hub targets were selected through PPI networking construction for further investigation. The enrichment analysis showed that protein kinase binding, mitogenactivated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were mainly involved. Molecular docking and MD simulation results supported good interaction between HSP90 protein and Austricin/Quercetin. The in vitro assay showed that TM inhibited the proliferation of HepG2 cells and the expression of HSP90AA1 gene.
This study is the first to use network pharmacology, molecular docking, MD simulation and cellular experiments to elucidate the active ingredients, molecular targets, and key biological pathways responsible for TM anti-HCC, providing a theoretical basis for further research.
We identified the active ingredients and targets of TM via HERB, PubChem, SwissADME, SwissTargetPrediction, and PharmMapper. We searched HCC targets from GeneCards, Comparative Toxicogenomics Database (CTD), and DisGeNET. Then, the intersection of drug targets and disease targets was uploaded to the STRING database to construct protein-protein interactions (PPI) networking whose topology parameters were analyzed in Cytoscape software to screen hub targets. Next, we used Metascape for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and we employed AutoDock vina, AMBER18 and PyMOL software along with several auxiliary tools for molecular docking and molecular dynamics (MD) simulation. Finally, based on the in silico findings, cellular experiments were conducted to investigate the effect of TM on HSP90AA1 gene expression.
A total of 228 targets and 35 active ingredients were identified. Twenty two hub targets were selected through PPI networking construction for further investigation. The enrichment analysis showed that protein kinase binding, mitogenactivated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were mainly involved. Molecular docking and MD simulation results supported good interaction between HSP90 protein and Austricin/Quercetin. The in vitro assay showed that TM inhibited the proliferation of HepG2 cells and the expression of HSP90AA1 gene.
This study is the first to use network pharmacology, molecular docking, MD simulation and cellular experiments to elucidate the active ingredients, molecular targets, and key biological pathways responsible for TM anti-HCC, providing a theoretical basis for further research.
摘要：
蒲公英（TM）是一种广泛使用的草药。有研究报道，TM对多种肿瘤表现出生长抑制和诱导凋亡，包括肝细胞癌（HCC）。活性成分，目标,TM抗HCC的分子机制有待进一步阐明。
我们通过HERB确定了TM的活性成分和靶标，PubChem,Swissadme,SwissTargetPrediction,和PharmMapper.我们从GeneCards中搜索了HCC目标，比较毒性基因组学数据库(CTD)，和DisGeNet。然后，将药物靶标和疾病靶标的交集上传到STRING数据库以构建蛋白质-蛋白质相互作用(PPI)网络,并在Cytoscape软件中分析其拓扑参数以筛选中心靶标.接下来,我们使用Metascape进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析，我们雇佣了AutoDockvina,AMBER18和PyMOL软件以及用于分子对接和分子动力学（MD）模拟的几种辅助工具。最后,根据计算机模拟发现，进行细胞实验以研究TM对HSP90AA1基因表达的影响。
总共鉴定了228个靶标和35种活性成分。通过PPI联网建设选择了22个枢纽目标进行进一步调查。富集分析表明,蛋白激酶结合,丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇3-激酶(PI3K)/Akt信号通路主要参与其中。分子对接和MD模拟结果支持HSP90蛋白与西霉素/槲皮素之间的良好相互作用。体外实验表明，TM抑制HepG2细胞的增殖和HSP90AA1基因的表达。
这项研究是第一个使用网络药理学，分子对接,MD模拟和细胞实验，以阐明活性成分，分子靶标,以及负责TM抗HCC的关键生物学途径，为进一步的研究提供了理论基础。
我们通过HERB确定了TM的活性成分和靶标，PubChem,Swissadme,SwissTargetPrediction,和PharmMapper.我们从GeneCards中搜索了HCC目标，比较毒性基因组学数据库(CTD)，和DisGeNet。然后，将药物靶标和疾病靶标的交集上传到STRING数据库以构建蛋白质-蛋白质相互作用(PPI)网络,并在Cytoscape软件中分析其拓扑参数以筛选中心靶标.接下来,我们使用Metascape进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）富集分析，我们雇佣了AutoDockvina,AMBER18和PyMOL软件以及用于分子对接和分子动力学（MD）模拟的几种辅助工具。最后,根据计算机模拟发现，进行细胞实验以研究TM对HSP90AA1基因表达的影响。
总共鉴定了228个靶标和35种活性成分。通过PPI联网建设选择了22个枢纽目标进行进一步调查。富集分析表明,蛋白激酶结合,丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇3-激酶(PI3K)/Akt信号通路主要参与其中。分子对接和MD模拟结果支持HSP90蛋白与西霉素/槲皮素之间的良好相互作用。体外实验表明，TM抑制HepG2细胞的增殖和HSP90AA1基因的表达。
这项研究是第一个使用网络药理学，分子对接,MD模拟和细胞实验，以阐明活性成分，分子靶标,以及负责TM抗HCC的关键生物学途径，为进一步的研究提供了理论基础。
