基于网络药理学探讨尪痹方治疗类风湿性关节炎的机制

doi:10.3976/j.issn.1002-4026.2023.03.005

摘要/Abstract

摘要：

基于网络药理学方法探讨尪痹方治疗类风湿性关节炎(rheumatoid arthritis,RA)的潜在机制。应用中药系统药理学数据库与分析平台筛选出尪痹方的化学成分及作用靶点,GeneCards数据库检索RA相关靶点,维恩图获取药物与疾病交集靶点,利用STRING数据库得到蛋白质-蛋白质相互作用( protein-protein interaction,PPI)网络信息,使用Cytoscape构建药物-有效成分-靶点-疾病网络与PPI网络图,通过DAVID数据库对共同靶点进行基因本体( gene ontology,GO)和京都基因与基因组百科全书( Kyoto encyclopedia of genes and genomes,KEGG)分析。使用SYBYL-X 2.1.1软件进行分子对接验证。经过筛选得到32个有效成分及99个相关靶点,核心靶点为IL-6、TNF、AKT1、VEGFA、PTGS2等。GO功能富集分析主要涉及RNA聚合酶II启动子转录的正调控等生物过程,KEGG 通路富集分析主要涉及TNF信号通路、T细胞受体信号通路、Toll样受体信号通路、破骨细胞分化等信号通路。分子对接结果显示,山柰酚、雷公藤内酯、柚皮素、川皮苷、刺芒柄花素等核心成分与IL-6、TNF、ATK1、PTGS2、VEGFA等的核心靶点蛋白之间具有良好的结合活性。本研究初步阐释了尪痹方通过多成分、多靶点治疗RA的潜在机制。

关键词: 网络药理学, 分子对接, 类风湿性关节炎, 尪痹方

Abstract:

Based on the research methods of network pharmacology, we discuss the potential mechanism of Wangbi formula in the treatment of rheumatoid arthritis (RA) in this article. The chemical components and action targets of the Wangbi formula were extracted using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The RA-related targets were retrieved from the GeneCards database, the intersection targets of drugs and diseases were obtained using a Venn diagram, and the protein-protein interaction (PPI) network information was obtained using the STRING database. Moreover, the Cytoscape software was used to create the network diagram of drug-active ingredient-target-diseases and PPI, and the common targets were analyzed using Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) from the DAVID database. Furthermore, the Sybyl-x 2.1.1 software was used for molecular docking validation. Screening yielded 32 active ingredients and 99 related targets, and the core targets were found to be IL-6, TNF, ATK1, PTGS2, VEGFA, etc. The GO function enrichment analysis mainly involved biological processes, such as positive regulation of RNA polymerase II promoter transcription, whereas KEGG pathway enrichment analysis mainly involved TNF, T-cell receptor, toll-like receptor, osteoclast differentiation, and other signaling pathways. The molecular docking results revealed that the core components, such as kaempferol, triptolide, naringenin, kaempferoside, and prickly shank anthocyanin, demonstrated good binding activity with the core targets, such as IL-6, TNF, ATK1, PTGS2, and VEGFA. This study provided a preliminary explanation of the multicomponent and multitarget mechanisms that may underlie the Wangbi formula's potential mechanism of action in the treatment of RA.

Key words: network pharmacology, molecular docking, rheumatoid arthritis, Wangbi formula

中图分类号:

R285

王一帆, 张艳艳, 田财军. 基于网络药理学探讨尪痹方治疗类风湿性关节炎的机制[J]. 山东科学, 2023, 36(3): 38-45.

WANG Yifan, ZHANG Yanyan, TIAN Caijun. Network pharmacology to explore the mechanism of Wangbi formula in the treatment of rheumatoid arthritis[J]. Shandong Science, 2023, 36(3): 38-45.

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来源	英文名称	化合物名称	来源	英文名称	化合物名称
雷公藤	hederagenin	红景天素	白芍	paeoniflorgenone	芍药黄酮
	(+)-Medioresinoldi-O-beta- D-glucopyranoside_qt	(+)-杜仲树脂酚双葡萄糖苷_qt		mairin	丁子香萜
	mairin	丁子香萜		kaempferol	山柰酚
	kaempferol	山柰酚		beta-sitosterol	β-谷甾醇
	beta-sitosterol	β-谷甾醇		sitosterol	谷甾醇
青风藤	16-epi-Isositsirikine	拉兹马宁碱	甘草	inermine	吲哚胺
	magnograndiolide	木兰内酯		DFV	DFV
	michelenolide	Michelenolide		glycyrol	甘氨酸