基于网络药理学探究薏苡仁干预脂肪性肝病的机制

doi:10.19586/j.2095-2341.2022.0191

生物技术进展 ›› 2023, Vol. 13 ›› Issue (2): 264-272.DOI: 10.19586/j.2095-2341.2022.0191

• 研究论文 • 上一篇

基于网络药理学探究薏苡仁干预脂肪性肝病的机制

董峰¹(), 皇甫秉欣²(), 徐佳², 许文涛³()

^1.中国中医科学院针灸研究所，北京 100700
^2.中国农业大学食品科学与营养工程学院，北京 100083
^3.中国农业大学食品科学与营养工程学院/北京食品营养与人类健康高精尖创新中心，北京 102627

收稿日期:2022-11-14 接受日期:2022-12-16 出版日期:2023-03-25 发布日期:2023-04-07
通讯作者: 许文涛
作者简介:董峰 E-mail: dongfeng2112@sina.com
皇甫秉欣 E-mail: bhuangfu@163.com；第一联系人：董峰与皇甫秉欣为本文共同第一作者

Mechanism Exploring of Coix Seed Intervention in Fatty Liver Disease Based on Network Pharmacology

Feng DONG¹(), Bingxin HUANGFU²(), Jia XU², Wentao XU³()

^1.Institute of Acupuncture and Moxibustion，China Academy of Chinese Medical Sciences，Beijing 100700，China
^2.College of Food Science and Nutritional Engineering，China Agricultural University，Beijing 100083，China
^3.Beijing Laboratory for Food Quality and Safety，College of Food Science and Nutritional Engineering，China Agricultural University，Beijing 102627，China

Received:2022-11-14 Accepted:2022-12-16 Online:2023-03-25 Published:2023-04-07
Contact: Wentao XU

摘要/Abstract

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

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

中图分类号:

R285

董峰, 皇甫秉欣, 徐佳, 许文涛. 基于网络药理学探究薏苡仁干预脂肪性肝病的机制[J]. 生物技术进展, 2023, 13(2): 264-272.

Feng DONG, Bingxin HUANGFU, Jia XU, Wentao XU. Mechanism Exploring of Coix Seed Intervention in Fatty Liver Disease Based on Network Pharmacology[J]. Current Biotechnology, 2023, 13(2): 264-272.

图/表 7

表1 薏苡仁9种活性成分

Table 1 Nine active compounds in coix seed

分子代码	活性成分	OB/%	DL
MOL000449	豆甾醇	43.83	0.76
MOL001323	谷甾醇α1	43.28	0.78
MOL001494	甘露醇	42.00	0.19
MOL000953	胆固醇	37.87	0.68
MOL000359	谷甾醇	36.91	0.75
MOL008121	2-单油酸甘油酯	34.23	0.29
MOL002882	单油酰甘油	34.13	0.30
MOL002372	(6Z,10E,14E,18E)-2,6,10,15,19,23-六甲基四碳酸-2,6,10,14,18,22-己烯	33.55	0.42
MOL008118	薏苡仁内酯	32.40	0.43

图1 薏苡仁-脂肪性肝病靶点交集韦恩图

Fig. 1 Venn diagram of “coix seed-fatty liver disease” target intersection

图2 薏苡仁有效成分与脂肪性肝病的PPI网络和可视化网络A: PPI网络模型；B: 可视化网络模型

Fig. 2 PPI network and visualized network of effective components in coix seed-fatty liver disease

表2 薏苡仁干预脂肪型肝病的主要活性成分

Table 2 Main active components of coix seed in the intervention of fatty liver disease

排序	活性成分	度值
1	谷甾醇	47
2	(6Z,10E,14E,18E)-2,6,10,15,19,23-六甲基四碳酸-2,6,10,14,18,22-己烯	46
3	豆甾醇	43
4	胆固醇	43
5	单油酰甘油	42
6	2-单油酸甘油酯	41
7	谷甾醇α1	41
8	薏苡仁内酯	40
9	甘露醇	37

图3 薏苡仁活性成分治疗脂肪性肝病靶点GO功能富集及KEGG通路分析A: GO功能富集分析； B: KEGG通路分析

Fig. 3 GO and KEGG analysis of gene targets, affected by the active components within coix seed in the treatment of fatty liver disease

图4 薏苡仁干预脂肪性肝病靶点-通路可视化网络

Fig. 4 Visual network of "target-pathway" indicating the coix seed intervention to fatty liver disease

图5 谷甾醇与EGFR、CASP3、AKT1、NOS3蛋白分子对接可视化模型

Fig. 5 Visualized docking model of sitosterol with EGFR, CASP3, AKT1 and NOS3 protein molecules

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基于网络药理学探究薏苡仁干预脂肪性肝病的机制

Mechanism Exploring of Coix Seed Intervention in Fatty Liver Disease Based on Network Pharmacology

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