基于网络药理学和分子对接研究三七抗类风湿关节炎的分子机制

doi:10.3976/j.issn.1002-4026.2022.02.005

摘要/Abstract

摘要：

通过中药系统药理学数据库与分析平台获取三七的主要活性成分及其相关靶点;通过GeneCards数据库预测类风湿关节炎相关靶点,并运用Uniprot数据库标准化蛋白名称,取三七-类风湿关节炎的交集靶点;通过STRING平台进行蛋白质-蛋白质相互作用分析;采用Metascape平台进行GO(gene ontology)功能分析和KEGG(Kyoto encyclopedia of genes and genomes)信号通路富集分析;采用Cytoscape3.7.2构建活性成分-靶点-信号通路相互作用网络;利用AutoDock Vina 1.1.2软件对关键靶点和成分进行分子对接。结果表明:通过筛选获得三七核心活性成分7种,三七-类风湿关节炎共同作用靶点100个,其中核心靶点包括AKT1、IL6、VEGFA、TNF、TP53、JUN、CASP3、PTGS2等;GO分析获得1 064条信号通路,KEGG分析得到102条信号通路,其中与类风湿关节炎相关的信号通路包括AGE-RAGE、MAPK、TNF、IL-17以及HIF-1等;分子对接结果显示关键靶点与成分具有较好的结合活性。研究认为三七抗类风湿关节炎可能是通过对物质代谢、信号转导、炎症反应等多靶点及多通路的调节从而发挥作用。

关键词: 网络药理学, 类风湿关节炎, 三七, 分子对接

Abstract:

Network pharmacology and molecular docking methods were used to study the molecular mechanism of Notoginseng Radix Et Rhizoma's action against rheumatoid arthritis. The main active ingredients and related targets of Notoginseng Radix Et Rhizoma were obtained through the Traditional Chinese Medicine systems pharmacology database and analysis platform (TCMSP). The GeneCards database was used to predict rheumatoid arthritis-related targets, and the Uniprot database was used to standardize protein names and obtain the intersection target of Notoginseng Radix Et Rhizoma and rheumatoid arthritis. The STRING platform was used to analyze protein-protein interactions, and the Metascape platform was used to perform gene ontology (GO) function analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis. Cytoscape 3.7.2 was used to construct the active ingredient-target-signaling pathway interaction network. In addition, the AutoDock Vina 1.1.2 software was used for molecular docking of key targets and components. On screening, 7 core active ingredients of Notoginseng Radix Et Rhizoma and 100 intersection targets for Notoginseng Radix Et Rhizoma and rheumatoid arthritis, e.g., AKT1, IL6, VEGFA, TNF, TP53, JUN, CASP3, and PTGS2 were obtained. GO and KEGG analyses derived 1064 and 102 signaling pathways, respectively; of which, the signaling pathways related to rheumatoid arthritis included AGE-RAGE, MAPK, TNF, IL-17, and HIF-1 signaling pathways. Furthermore, molecular docking results showed that the key targets and components had a good binding activity. Therefore, our results suggest that Notoginseng Radix Et Rhizoma may play a role in preventing rheumatoid arthritis by the regulation of multiple targets and pathways, such as metabolism, signal transduction, and inflammatory pathways.

Key words: network pharmacology, rheumatoid arthritis, Notoginseng Radix Et Rhizoma, molecular docking

中图分类号:

R285

张潇文,应天昊,梁美辰,王艳芳,王信林,张雷明. 基于网络药理学和分子对接研究三七抗类风湿关节炎的分子机制[J]. 山东科学, 2022, 35(2): 36-45.

ZHANG Xiao-wen,YING Tian-hao,LIANG Mei-chen,WANG Yan-fang,WANG Xin-lin,ZHANG Lei-ming. Molecular mechanism of Notoginseng Radix Et Rhizoma's action against rheumatoid arthritis based on network pharmacology and molecular docking[J]. Shandong Science, 2022, 35(2): 36-45.

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编号	代号	中文名称	英文名称	OB/%	DL
MOL001494	SQ1	亚油酸乙酯	mandenol	42.00	0.19
MOL001792	SQ2	甘草素	liquiritigenin	32.76	0.18
MOL002879	SQ3	邻苯二甲酸二异辛酯	diop	43.59	0.39
MOL000358	SQ4	β-谷甾醇	beta-sitosterol	36.91	0.75
MOL000449	SQ5	豆甾醇	stigmasterol	43.83	0.76
MOL005344	SQ6	人参皂苷rh2	ginsenoside rh2	36.32	0.56
MOL000098	SQ7	槲皮素	quercetin	46.43	0.28

标记	编号	名称	连接度	介度	紧密度
SQ7	MOL000098	槲皮素	68	0.341 3	0.744 2
SQ6	MOL005344	人参皂苷rh2	9	0.008 0	0.385 5
SQ4	MOL000358	β-谷甾醇	7	0.000 9	0.373 5
SQ5	MOL000449	豆甾醇	2	0.000 3	0.332 2
SQ1	MOL001494	亚油酸乙酯	1	0.000 0	0.325 4
SQ2	MOL001792	甘草素	1	0.000 0	0.275 1

靶点	连接度	介度	紧密度
AKT1	19	0.018 8	0.533 3
RELA	19	0.018 1	0.533 3
MAPK1	18	0.017 7	0.527 5
IL6	16	0.013 1	0.516 1
CHUK	16	0.011 9	0.510 6
TNF	15	0.013 3	0.510 6
NFKBIA	15	0.012 6	0.510 6
JUN	15	0.013 2	0.510 6
CASP3	15	0.014 7	0.510 6
TP53	14	0.009 4	0.500 0

编号	化合物名称	结合自由能/(kJ·mol^-1)
MOL000098	槲皮素	-6.2
MOL000358	β-谷甾醇	-6.9
MOL000449	豆甾醇	-7.1
MOL001494	亚油酸乙酯	-4.3
MOL001792	甘草素	-6.4
MOL005344	人参皂苷rh2	-7.1