利用网络药理学确定薏苡仁作用肝癌的有效活性成分

Use of network pharmacology to determine the active ingredients of Coicis Semen on liver cancer

基于网络药理学预测薏苡仁治疗肝癌的有效活性成分及靶点。运用TCMSP数据库筛选薏苡仁的有效活性成分;ChEMBL及TCMSP数据库预测薏苡仁有效活性成分对应的靶点;运用GeneCards数据库,TTD数据库,GAD数据库和TCMSP数据库筛选肝癌的相关靶点;通过Cytoscape软件建立利用"薏苡仁有效活性成分-肝癌疾病靶点"网络模型;DAVID数据库对"薏苡仁有效活性成分-肝癌疾病靶点"进行GO注释分析和KEGG通路分析。通过Discovery Studio软件对薏苡仁有效活性成分与作用靶点进行分子对接验证。该研究筛选得到薏苡仁15个有效成分,与肝癌相关的靶点有13个及相关信号通路7条。网络分析结果表明薏苡仁可能通过作用于TERT,CYP3A4,NR1H3,ALDH1A1,ESR1,SLCO1B3,SRD5A2,CYP1A2,CYP2D6,FABP1等关键靶点发挥抗肝癌作用。分子对接结果显示SRD5A2蛋白与薏苡仁成分对接评分最高,而薏苡仁成分中以sitosterol,stigmasterol,oleic acid 3个成分与SRD5A2蛋白结合作用最强。该研究初步揭示了薏苡仁治疗肝癌具有多靶点、多通路的优点,通过网络药理学方法研究薏苡仁抗肝癌的有效成分及潜在作用机制,为进一步验证薏苡仁抗肝癌的分子机制提供了新思路。

Objective:To predict the active components and targets of Coicis Semen in the treatment of liver cancer based on network pharmacology.Methods:TCMSP database was used to screen the active components of Coicis Semen,while ChEMBL and TCMSP database were used to predict the corresponding targets of Coicis Semen.In addition,GeneCards database,TTD database,GAD database and TCMSP database were used to screen the related targets of liver cancer.The network model of"Coicis Semen components-targets of liver cancer disease"was then established by using Cytoscape software.David database GO annotation analysis and KEGG pathway analysis were carried out for"Coicis Semen active component liver cancer target".Results:Through the Discovery Studio software,the molecular docking between the effective active components and the target of Coicis Semen was verified.In this study,15 active components of Coicis Semen,13 targets related to liver cancer and 7 related signal pathways were screened.The results of network analysis showed that Coicis Semen may play an anti-hepatoma role by acting on key targets such as TERT,CYP3A4,NR1H3,ALDH1A1,ESR1,SLCO1B3,SRD5A2,CYP1A2,CYP2D6 and FABP1.The results of molecular docking showed that SRD5A2 protein had the highest docking score with Coicis Semen,and the three components of Coicis Semen,sitosterol,stigmasterol and oleic acid,had the strongest binding effect with SRD5A2 protein.Conclusion:This study preliminarily revealed that Coicis Semen has the advantages of multi-target and multi-channel in the treatment of liver cancer.By using the method of network pharmacology,the effective components and potential anti-liver cancer mechanism of Coicis Semen were studied,which provided a new way to further verify the molecular anti-liver cancer mechanism of Coicis Semen.