基于网络药理学与分子对接探究麻黄-桂枝药对治疗类风湿性关节炎机制

史丽颖; 温泽宇; 宋昱; 于大永

doi:10.6054/j.jscnun.2023021

基于网络药理学与分子对接探究麻黄-桂枝药对治疗类风湿性关节炎机制

doi: 10.6054/j.jscnun.2023021

大连大学生命科学与技术学院，大连 116622

基金项目:

国家自然科学基金项目 82274075

详细信息

通讯作者:
于大永，Email: yudayong@dlu.edu.cn

中图分类号: R285
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- 文章访问数: 76
- HTML全文浏览量: 11
- PDF下载量: 13
- 被引次数: 0
出版历程
- 收稿日期: 2021-06-11
- 网络出版日期: 2023-06-14
- 刊出日期: 2023-04-25

Mechanism of Ephedra-Guizhi in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

School of Life Science and Biotechnology, Dalian University, Dalian 116622, China

摘要

摘要: 通过TCMSP数据库检索麻黄、桂枝中的活性成分以及对应的靶点蛋白，在GeneCards数据库中以“rheumatoid arthritis”为关键词检索类风湿性关节炎(RA)的相关靶点，将收集的2类靶点相互映射取交集后通过STRING平台构建PPI网络，利用Cytoscape软件进行可视化分析；借助David 6.8数据库，对交集靶点进行GO与KEGG富集分析；最后利用Schrodinger软件对核心靶点与关键活性成分进行分子对接验证。2类靶点映射得到交集靶点共134个，PPI分析得到核心靶点为AKT1、IL6、TP53、RELA和CCND1。GO与KEGG富集分析得到关键信号通路为TNF信号通路、Toll样受体信号通路和PI3K-Akt信号通路。分子对接结果显示槲皮素、木犀草素、二氢槲皮素与AKT1、IL6、TP53有较好的结合效果。研究推测麻黄-桂枝药对中的活性成分可能通过抑制炎性介质表达、抑制关节滑膜中树突细胞以及巨噬细胞过量增殖等途径来阻止RA病理发展进程。
- 网络药理学 /
- 类风湿性关节炎 /
- 作用机制 /
- 麻黄-桂枝药对 /
- 分子对接
Abstract: The active components and corresponding target proteins in Ephedra and Guizhi were retrieved through TCMSP database, and Rheumatoid Arthritis(RA) related targets were retrieved with "rheumatoid arthritis" as the keyword in GeneCards database. After the collected two types of targets were mapped and intersected with each other, PPI network was constructed through STRING platform, and visual analysis was carried out by Cytoscape software. At the same time, the intersection targets were enriched and analyzed by GO and KEGG with the help of David 6.8 database. Finally, the core target and key active components were docking verified by Schrodinger software. Two kinds of targets are mapped, there are 134 intersection targets. PPI analysis shows that the core targets are AKT1, IL6, TP53, RELA and CCND1. Go and KEGG enrichment analysis showed that the key signal pathways were TNF signal pathway, Toll like receptor signal pathway and PI3K-Akt signal pathway. Molecular docking results showed that quercetin, luteolin and dihydroquercetin had good binding effects with AKT1, IL6 and TP53. It is concluded that the active components of Ephedra-Guizhi may play a role in the treatment of rheumatoid arthritis by inhibiting the expression of inflammatory mediators and suppressing the excessive proliferation of dendritic cells and macrophages in joint synovium to prevent pathological progression of RA.
- network pharmacology /
- rheumatoid arthritis /
- mechanism of action /
- Ephedra-Guizhi drug pair /
- molecu-lar docking

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图 1 药材-活性成分-靶点网络

注：节点大小以及透明度依据degree值区分。

Figure 1. The network of medicinal materials-active ingredients-targets

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图 2 麻黄-桂枝药对中的活性成分对应的候选靶点与RA相关靶点映射交集

Figure 2. The intersection mapping of candidate targets corresponding to active ingredients in Ephedra-Guizhi drug pair and RA related targets

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图 3 麻黄-桂枝药对中的活性成分-交集靶点网络

注：图中左侧为活性成分，右侧为交集靶点。

Figure 3. The network of active ingredients in Ephedra-Guizhi drug pair-intersection targets

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图 4 交集靶点蛋白相互作用网络图

Figure 4. PPI network of intersection targets

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图 5 GO和KEGG分析

Figure 5. The GO and KEGG analysis

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图 6 活性成分-靶点-信号通路图

Figure 6. The network of active ingredients-targets-pathways

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图 7 化合物-核心靶点3D作用方式

Figure 7. The diagram of compound-core target 3D mode of action

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表 1 麻黄-桂枝药对中的活性成分

Table 1. Active ingredients in Ephedra-Guizhi drug pair

MOL ID	来源	代号	化合物	OB/%	DL
MOL010788	麻黄	MH1	leucopelargonidin	57.97	0.24
MOL002823	麻黄	MH2	herbacetin	36.07	0.27
MOL010489	麻黄	MH3	resivit	30.84	0.27
MOL000422	麻黄	MH4	kaempferol	41.88	0.24
MOL004798	麻黄	MH5	delphinidin	40.63	0.28
MOL000098	麻黄	MH6	quercetin	46.43	0.28
MOL000006	麻黄	MH7	luteolin	36.16	0.25
MOL000449	麻黄	MH8	stigmasterol	43.83	0.76
MOL001494	麻黄	MH9	mandenol	42.00	0.19
MOL001755	麻黄	MH10	24-Ethylcholest-4-en-3-one	36.08	0.76
MOL001771	麻黄	MH11	poriferast-5-en-3beta-ol	36.91	0.75
MOL002881	麻黄	MH12	diosmetin	31.14	0.27
MOL004328	麻黄	MH13	naringenin	59.29	0.21
MOL005043	麻黄	MH14	campest-5-en-3beta-ol	37.58	0.71
MOL005190	麻黄	MH15	eriodictyol	71.79	0.24
MOL005573	麻黄	MH16	genkwanin	37.13	0.24
MOL005842	麻黄	MH17	pectolinarigenin	41.17	0.30
MOL007214	麻黄	MH18	(+)-Leucocyanidin	37.61	0.27
MOL011319	麻黄	MH19	truflex OBP	43.74	0.24
MOL001736	桂枝	GZ1	(-)-taxifolin	60.51	0.27
MOL000359	桂枝	GZ2	sitosterol	36.91	0.75
MOL000073	桂枝	GZ3	ent-Epicatechin	48.96	0.24
MOL000358	麻黄/桂枝	A1	beta-sitosterol	36.91	0.75
MOL000492	麻黄/桂枝	A2	(+)-catechin	54.83	0.24
MOL004576	麻黄/桂枝	A3	taxifolin	57.84	0.27
注：OB为口服生物利用度，DL为类药性。

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表 2 排名前20的信号通路

Table 2. The information of top 20 pathways

编号	信号通路	靶蛋白富集数/个	P值	关键靶点
1	Hepatitis B	35	2.35E-29	TP53、JUN、AKT1、FOS、IL6、RELA、CCND1
2	Pathways in cancer	50	3.13E-29	TP53、JUN、AKT1、FOS、IL6、RELA、EGFR、CCND1
3	Bladder cancer	20	4.19E-23	TP53、EGFR、CCND1
4	Pancreatic cancer	23	5.62E-23	TP53、AKT1、RELA、EGFR、CCND1
5	TNF signaling pathway	25	2.92E-20	JUN、AKT1、FOS、IL6、RELA
6	Prostate cancer	22	2.06E-18	TP53、AKT1、RELA、EGFR、CCND1
7	Chagas disease (American trypanosomiasis)	23	4.88E-18	JUN、AKT1、FOS、IL6、RELA
8	Chronic myeloid leukemia	20	1.24E-17	TP53、AKT1、RELA、CCND1
9	Toxoplasmosis	22	2.76E-16	AKT1、RELA
10	Glioma	18	8.37E-16	TP53、AKT1、EGFR、CCND1
11	Proteoglycans in cancer	27	1.13E-15	TP53、AKT1、EGFR、CCND1
12	Non-small cell lung cancer	17	1.32E-15	TP53、AKT1、EGFR、CCND1
13	HIF-1 signaling pathway	20	4.25E-15	AKT1、IL6、RELA、EGFR
14	Colorectal cancer	17	8.17E-15	TP53、JUN、AKT1、FOS、CCND1
15	Toll-like receptor signalingpathway	20	2.93E-14	JUN、AKT1、FOS、IL6、RELA
16	Melanoma	17	8.37E-14	TP53、AKT1、EDFR、CCND1
17	Small cell lung cancer	18	1.1E-13	TP53、AKT1、RELA、CCND1
18	PI3K-Akt signaling pathway	31	3.32E-13	TP53、AKT1、IL6、RELA、EGFR、CCND1
19	Influenza A	23	4.15E-13	JUN、AKT1、IL6、RELA
20	Leishmaniasis	16	1.45E-12	JUN、FOS、RELA

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表 3 关键活性成分与5个核心靶点的对接分数

Table 3. Docking information of key active ingredients and five core targets

化合物	结构	CAS号	对接分数/(kcal·mol^-1)
化合物	结构	CAS号	TP53	AKT1	IL6	RELA	CCND1
槲皮素		117-39-5	-8.119	-7.243	-6.321	-5.317	-5.364
木犀草素		491-70-3	-8.713	-7.537	-6.452	-5.428	-5.412
二氢槲皮素		480-18-2	-8.442	-7.738	-5.341	-5.786	-5.874
山奈酚		25615-14-9	-6.493	-7.231	-3.698	-5.228	-5.012
柚皮苷		158196-34-0	-7.430	-7.193	-3.514	-5.661	-4.312
β-谷甾醇		83-46-5	-5.700	-5.241	-3.574	-4.657	-3.162

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