Abstract:

This article aimed to predict the active ingredients and mechanisms of coix seed in the treatment of fatty liver disease， by using network pharmacology and molecular docking technique. The TCMSP database was used to screen the coix seed's active ingredients； PharmMapper， Uniprot， Disgenet， and Venny 2.1.0 databases were used to predict the intersections of relevant gene targets of coix seed and fatty liver disease； String 11.0 was used to create the "protein-protein interaction" network. A cluster-profiler data package was used to perform gene ontology （GO） and the target kyoto encyclopedia of genes and genomes （KEGG） analysis. Cytoscape 3.8.2 software was used to calculate network topology parameters and visualize networks. PubChem， AlphaFold， and CB-DOCK databases were used to obtain small molecular substances and protein structures and perform molecular docking. This research predicted the potential and molecular mechanism of coix seed in the intervention of fatty liver disease. Sitosterol， one of the 9 active ingredients in coix seed， impact fatty liver disease. From the genetic aspect， coix seed interferes with fatty liver disease by regulating genes such as Epidermal Growth Factor Receptor （EGFR）， Caspase-3 （CASP3）， AKT Serine/Threonine Kinase 1 （AKT1）， and Nitric Oxide Synthase 3 （NOS3）； from the pathway aspect，coix seed acts on alcoholic liver disease， endocrine resistance， and estrogen signaling pathways. Coix seed affects fatty liver disease through multiple gene targets and pathways.

Key words: coix seed, fatty liver disease, network pharmacology, sitosterol, molecular docking

摘要：

通过网络药理学和分子对接，预测薏苡仁治疗脂肪性肝病的作用机制。利用TCMSP、PharmMapper、Uniprot、Disgenet和Venny 2.1.0软件预测薏苡仁活性成分与脂肪性肝病基因靶点交集，利用String 11.0数据库绘制靶点蛋白互作网络模型；使用“Cluster-Profiler数据包”对靶点进行基因本体论（gene ontology, GO）和京都基因和基因组百科全书（kyoto encyclopedia of genes and genomes, KEGG）富集分析；通过Cytoscape-3.8.2 软件计算网络拓扑参数、绘制可视化网络。利用PubChem、AlphaFold和CB-Dock数据库获取小分子物质和蛋白结构，并进行分子对接。首次预测了薏苡仁干预脂肪性肝病的潜力及其分子机制。薏苡仁的9个活性成分中，谷甾醇在干预脂肪性肝病中发挥重要作用。在转录水平上，薏苡仁通过调节EGFR、CASP3、AKT1、NOS3等基因干预脂肪性肝病；在通路水平上，薏苡仁主要作用于酒精性脂肪肝、内分泌抵抗、雌激素通路。结果表明，薏苡仁通过多个靶点、多通路影响脂肪性肝病。

关键词: 薏苡仁, 脂肪性肝病, 网络药理, 谷甾醇, 分子对接