基于网络药理学和分子对接探究麻黄加术汤治疗类风湿关节炎的潜在作用机制

doi:10.3976/j.issn.1002-4026.2022.03.003

摘要/Abstract

摘要：

利用网络药理学和分子对接方法探究麻黄加术汤治疗类风湿关节炎的潜在作用机制。通过数据库检索、筛选得到麻黄加术汤主要活性成分及其作用靶点,通过GeneCards、OMIM和Drugbank数据库筛选得到类风湿关节炎疾病靶点,使用STRING数据库和Cytoscape软件构建PPI(protein-protein interaction)网络;使用Metascape数据库对麻黄加术汤治疗类风湿关节炎的作用靶点进行GO(gene ontology)和KEGG(Kyoto encyclopedia of genes and genomes)富集分析;Cytoscape软件构建药物成分-靶点-通路网络;使用AutoDock软件对关键成分和靶点进行分子对接。结果筛选得到麻黄加术汤的潜在活性成分共131个,治疗类风湿关节炎的关键靶点133个,主要成分包括槲皮素、木犀草素、山奈酚等,关键靶点包括IL-6、TNF、TP53、STAT3等。GO和KEGG分析显示生物过程2 250条,细胞成分89条,分子功能152条,富集通路主要涉及AGE-RAGE信号通路、IL-17信号通路和TNF信号通路等。分子对接结果显示Phaseol和甘草酚与AKT1、PTGS2、MAPK1、MAPK8等关键靶点具有较好的结合活性。研究发现麻黄加术汤是通过多成分、多靶点、多通路的作用方式发挥治疗类风湿关节炎的作用,为类风湿关节炎的治疗提供了重要的科学信息。

关键词: 麻黄加术汤, 类风湿关节炎, 网络药理学, 分子对接

Abstract:

To explore the potential mechanism of Mahuangjiazhu Decoction in the treatment of rheumatoid arthritis using network pharmacology and molecular docking technology. The main active ingredients of Mahuangjiazhu Decoction and their targets were searched and screened. The targets for rheumatoid arthritis disease were obtained by screening using the GeneCards, OMIM, and Drugbank databases. STRING database and Cytoscape software were used to construct protein-protein interaction networks. Metascape database was used to conduct gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses of the target points of Mahuangjiazhu Decoction in the treatment of rheumatoid arthritis. Cytoscape was used to construct a drug components-targets-pathways network. Finally, AutoDock software was used to perform molecular docking of key components and targets. A total of 131 potential active ingredients of Mahuangjiazhu Decoction and 133 key targets for the treatment of rheumatoid arthritis were screened. The main ingredients included quercetin, luteolin, kaempferol, etc. The core targets included IL-6, TNF, TP53, STAT3, etc. GO and KEGG analyses revealed 2 250 biological processes, 89 cell components, and 152 molecular functions. The enrichment pathways mainly involved the AGE-RAGE, IL-17, and TNF signaling pathways. The results of molecular docking showed that phaseol and glycyrrhizin had good binding activity to key targets such as AKT1, PTGS2, MAPK1, and MAPK8. Thus, Mahuangjiazhu Decoction plays a role in the treatment of rheumatoid arthritis through a multi-component, multi-target, and multi-channel action mode, which provides important scientific information for the treatment of rheumatoid arthritis.

Key words: :Mahuangjiazhu Decoction, rheumatoid arthritis, network pharmacology, molecular docking

中图分类号:

R285.5

李晓丽,应天昊,唐一迪,祝璇,孙萌萌,余涛,赵佳宁,张雷明. 基于网络药理学和分子对接探究麻黄加术汤治疗类风湿关节炎的潜在作用机制[J]. 山东科学, 2022, 35(3): 17-26.

LI Xiao-li,YING Tian-hao,TANG Yi-di,ZHU Xuan,SUN Meng-meng,YU Tao,ZHAO Jia-ning,ZHANG Lei-ming. Potential mechanism of Mahuangjiazhu Decoction in the treatment of rheumatoid arthritis based on network pharmacology combined with molecular docking technology[J]. Shandong Science, 2022, 35(3): 17-26.

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编号		活性成分	来源
MOL002311		Glycyrol(甘草酚)	甘草、杏仁
MOL012922		l-SPD(左旋千金藤啶碱)	杏仁
MOL004990		7,2',4'-trihydroxy-5-methoxy-3-arylcoumarin(7,2',4'-三羟基-5-甲氧基-3-苯基香豆素)	甘草
MOL004904		Licopyranocoumarin(甘草吡喃香豆素)	甘草
MOL004891		Shinpterocarpin	甘草
MOL007207		Machiline(乌药碱)	杏仁
MOL005017		Phaseol	甘草、杏仁
MOL004841	Licochalcone B(甘草查尔酮B)			甘草、杏仁
MOL004810	glyasperin F(粗毛甘草素F)			甘草
MOL001484	Inermine(高丽槐素)			甘草
MOL000500	Vestitol(维斯体素)			甘草
MOL005007	Glyasperins M(粗毛甘草素M)			甘草
MOL005190	Eriodictyol(圣草酚)			麻黄
MOL004941	(2R)-7-hydroxy-2-(4-hydroxyphenyl)chroman-4-one			甘草
MOL004959	1-Methoxyphaseollidin(1-甲氧基菜豆素)			甘草
MOL000392	Formononetin(刺芒柄花素)			甘草
MOL003410	Ziziphin_qt			杏仁
MOL004863	3-(3,4-dihydroxyphenyl)-5,7-dihydroxy-8-(3-methylbut-2-enyl)chromone			甘草
MOL004903	Liquiritin(甘草苷)			甘草、杏仁
MOL004808	glyasperin B(粗毛甘草素B)			甘草

靶点	靶点名称	度值	靶点	靶点名称	度值
IL-6	白介素6	65	MMP9	基质金属蛋白酶-9	42
TNF	肿瘤坏死因子	58	EGF	促表皮生长因子	41
TP53	细胞肿瘤抗原 p53	55	EGFR	表皮生长因子受体	40
STAT3	信号转导和转录激活因子3	55	PTGS2	前列腺素内过氧化物合酶 2	40
AKT1	蛋白激酶B	54	CCL2	C-C趋化因子 2	39
VEGFA	血管内皮生长因子 A	53	RELA	转录因子p65	39
CXCL8	白介素8	50	APP	淀粉样前体蛋白	37
JUN	c-Jun氨基末端激酶	50	ICAM1	胞间黏附分子 1	37
MAPK8	丝裂原活化蛋白激酶 8	49	MYC	Myc原癌基因蛋白	36
MAPK1	丝裂原活化蛋白激酶 1	48	IL-10	白介素10	36
IL-1β	白介素1-β	47	SRC	类固醇受体共激活因子	35

活性成分	结合自由能/(kJ·mol^-1)
活性成分	AKT1	PTGS2	MAPK1	MAPK8	RELA	STAT3	CXCL8	IL1B	IL6	TNF
槲皮素	-9.5	-9.6	-8.4	-7.6	-7.3	-7.3	-6.6	-7.0	-7.1	-6.7
木犀草素	-9.5	-9.4	-8.4	-8.1	-6.9	-7.8	-6.5	-6.8	-7.0	-6.2
山奈酚	-9.5	-9.7	-8.2	-7.5	-7.3	-7.0	-6.7	-6.7	-6.7	-6.3
柚皮素	-9.6	-9.1	-7.9	-7.6	-7.0	-7.7	-6.3	-6.9	-6.8	-6.4
刺芒柄花素	-9.7	-9.1	-7.9	-7.5	-7.1	-6.9	-6.8	-6.4	-6.3	-5.8
甘草酚	-10.6	-10.3	-9.3	-8.9	-7.1	-7.7	-6.8	-7.2	-6.6	-6.9
花旗松素	-9.6	-9.4	-8.1	-7.8	-7.0	-7.4	-6.6	-7.1	-6.7	-6.5
(+)-儿茶素	-9.9	-9.2	-8.5	-8.8	-7.5	-7.4	-7.2	-7.7	-7.3	-7.3
甘草查尔酮 B	-9.5	-8.5	-7.4	-7.2	-6.6	-6.6	-6.0	-6.4	-6.2	-5.8
Phaseol	-11.2	-10.2	-9.4	-9.0	-7.7	-8.1	-7.0	-7.3	-7.7	-7.3
光甘草定	-9.7	-8.4	-8.0	-8.8	-8.6	-7.7	-6.8	-7.5	-7.3	-6.4
β-谷甾醇	-10.8	-8.3	-9.1	-8.7	-6.9	-7.9	-6.9	-7.7	-7.3	-7.0