基于网络药理学和分子对接研究龙葵治疗肝癌的分子机制

Study on molecular mechanism of Solanum nigrum in treatment of hepatocarcinoma based on network pharmacology and molecular docking

该研究通过网络药理学和分子对接的方法,对龙葵治疗肝癌的主要活性成分及其潜在作用机制进行探讨。首先,通过中药系统药理学数据库与分析平台(TCMSP)获取龙葵的主要活性成分及其预测靶点。然后,检索OncoDB.hcc和PharmDB-K数据库获取肝癌相关的疾病靶点;再将疾病靶点与药物预测靶点进行交集,筛选出共同的肝癌靶点。接着,运用String数据库结合Cytoscape软件绘制肝癌靶点的蛋白相互作用网络(PPI);并运用Cytoscape的ClueGO和CluePedia插件对肝癌靶点进行生物学功能分析和网络构建。最后,通过DISCOVERY STUDIO软件对龙葵的关键活性成分与作用靶点进行分子对接验证。该研究筛选出龙葵4个活性成分,涉及22个肝癌靶点及相关信号通路7个。网络分析结果表明龙葵可能通过作用于EGFR,TP53,MYC,CCND1,CTNNB1等关键靶点发挥抗肝癌作用。分子对接结果显示槲皮素(quercetin)和EGFR能稳定地结合并通过氨基酸残基LEU718,LYS745,GLN791等发生相互作用。该研究初步揭示了龙葵治疗肝癌具有多靶点、多通路的潜在作用机制,为后续验证龙葵抗肝癌的分子机制提供了思路。

This study aimed to explore the main active ingredients and potential targets of Solanum nigrum(SN),so as to reveal the potential molecular mechanism of SN in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and molecular docking.First,the main active ingredients and predictive targets of SN were collected in the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).Then,the targets relating to HCC were collected through retrieval of integrated bio-pharmacological network database for traditional Korean medicine(PharmDB-K),oncogenomic database of hepatocellular carcinoma(OncoDB.hcc).The common targets of disease-drug component were selected through intersection between predictive targets and disease targets.Next,based on the String platform,protein-protein interaction network(PPI)model of the potential anti-HCC targets was constructed using the software Cytoscape 3.7.1.ClueGO and CluePedia APP in Cytoscape were used to analyze the gene function of SN in the treatment of HCC,and construct the main active ingredients-potential targets-signal pathways topology network of SN.Finally,DISCOVERY STUDIO software was applied in verifying the molecular docking between the key active ingredient and potential protein target.The results showed that there were 4 main active ingredients of SN,involving 22 potential targets relating to HCC and 7 signal pathways relating to potential anti-HCC targets of SN.Network analysis showed that SN may play a therapeutic role in HCC by acting on key targets,such as EGFR,TP53,MYC,CCND1 and CTNNB1.Molecular docking results showed that quercetin and EGFR could bind stably and interact through amino acid residues LEU718,LYS745 and GLN791.This study revealed the potential active ingredients and the possible molecular mechanism of SN for treatment of HCC,providing scientific basis for follow-up exploration of the molecular mechanism of SN against HCC.