基于网络药理学和分子对接分析参附汤治疗房颤的作用机制

施伟华; 巢潇莺; 苏泳兴; 李烁; 李晓莉; 钟国强

doi:10.16766/j.cnki.issn.1674-4152.002440

基于网络药理学和分子对接分析参附汤治疗房颤的作用机制

doi: 10.16766/j.cnki.issn.1674-4152.002440

广西医科大学第一附属医院心血管内科，广西南宁 530021

基金项目:

国家自然科学基金项目 82060068

详细信息

通讯作者:
钟国强，E-mail: gq_zhong@126.com

中图分类号: R541.75 R96
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- 被引次数: 0
出版历程
- 收稿日期: 2021-08-19
- 网络出版日期: 2022-09-05

Mechanism of Shenfu Decoction in the treatment of atrial fibrillation based on network pharmacology and molecular docking

Cardiovascular Department, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China

摘要

摘要: 目的基于网络药理学和分子对接技术，探索参附汤治疗房颤的作用机制。方法 2020年3—4月通过TCMSP数据库筛选参附汤的活性成分以及相关靶点，并在Uniprot数据库中对相关靶点进行注释并得到基因名；在OMIM和Pharmgkb等数据库，获取房颤相关的靶点；由R软件对房颤及其与参附汤有效成分靶点取交集，获得关键治疗靶点；利用String数据库构建PPI网络，并将结果导入Cytoscape软件中构建“活性成分-作用靶点-疾病”网络和进行拓扑分析，获得核心靶点；随后在DAVID数据库对关键靶点进行GO功能注释及KEGG富集分析，最后通过AutoDock Vina软件对关键成分和核心靶点进行分子对接。结果获得参附汤靶点101个，房颤靶点3 219个，交集后获得65个共有靶点，拓扑分析发现NFKBIA、RELA、IL1B、JUN、STAT1、MAPK8是参附汤治疗房颤的核心靶点；GO提示主要靶点涉及电压门控钙通道活性、钙离子传输以及活性氧代谢等生物学过程；KEGG提示主要靶点通过cGMP-PKG、cAMP、钙通道以及PI3K-Akt等信号通路参与治疗房颤；分子对接结果显示核心靶点蛋白与对应参附汤活性成分具有较好的结合稳定性。结论参附汤治疗房颤具有“多成分-多靶点-多通路”的作用特点，可能与NFKBIA、RELA、IL1B、JUN、STAT1、MAPK8靶点相关，其具体机制尚需分子生物实验印证。
- 参附汤 /
- 房颤 /
- 作用机制 /
- 网络药理学 /
- 分子对接
Abstract: Objective To explore the mechanism of Shenfu Decoction in the treatment of atrial fibrillation by network pharmacology and molecular docking technology. Methods The main active ingredients of Shenfu Decoction were screened by the TCMSP database, and the related targets were annotated by the Uniprot database and gene names were obtained. The targets of atrial fibrillation were obtained from the OMIM and Pharmgkb Databases. R software was used to determine the intersection of atrial fibrillation and the active ingredient targets of Shenfu Decoction, and the therapeutic targets were obtained. The PPI network was constructed by using the online String database, and the results were imported into Cytoscape software to construct the "active ingredient-target-disease" network and perform topology analysis to obtain the core targets. The GO and KEGG enrichment analyses of key targets in the DAVID database were carried out, and AutoDock Vina software was applied to conduct molecular docking of key components and key targets. Results The 101 targets of Shenfu Decoction and 3 219 targets of atrial fibrillation were obtained, and 65 common targets were obtained after the intersection. Topology analysis showed that NFKBIA, RELA, IL1B, JUN, STAT1 and MAPK8 might be the core targets of Shenfu Decoction in treating AF. GO suggested that the targets involved biological processes such as voltage-gated calcium channel activity, calcium ion transport and reactive oxygen metabolism. KEGG suggested that the targets were involved in the treatment of atrial fibrillation through cGMP-PKG, cAMP, calcium channel and PI3K-Akt signalling pathways. The results of molecular docking showed that the core target protein had good binding stability with the corresponding active components. Conclusion The treatment of atrial fibrillation with Shenfu Decoction has the characteristics of "multi-component, multi-target and multi-pathway", which may be related to targets of NFKBIA, RELA, IL1B, JUN, STAT1 and MAPK8. The specific mechanisms may need to be confirmed by molecular biological experiments.
- Shenfu Decoction /
- Atrial fibrillation /
- Mechanism /
- Network pharmacology /
- Molecular docking

HTML全文

图 1 房颤靶点

Figure 1. Atrial fibrillation targets

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图 2 参附汤治疗房颤“有效成分-靶点-疾病”网络

Figure 2. Shenfu Decoction for the treatment of atrial fibrillation "active components - targets - diseases" network

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图 3 PPI网络图

Figure 3. PPI network diagram

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图 4 GO富集分析分类

注：BP为biological process，生物过程；MF为molecular function，分子功能；CC为cellular component，细胞组分。

Figure 4. GO enrichment analysis classification

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图 5 分子对接图

注：仅展示结合能 < -7.0 kcal/mol对接图，由左往右分别为NFKBIA与ginsenoside rh2对接图，RELA与kaempferol对接图，JUN与beta-sitosterol对接图。

Figure 5. Molecular docking diagram

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表 1 参附汤治疗房颤关键靶点KEGG通路分析

Table 1. KEGG pathway analysis of the key target of Shenfu Decoction in treating atrial fibrillation

ID	通路	数量/个	P值
hsa05417	Lipid and atherosclerosis	24	1.40×10^-20
hsa05200	Pathways in cancer	20	2.64×10^-10
hsa05418	Fluid shear stress and atherosclerosis	16	2.03×10^-13
hsa05167	Kaposi sarcoma-associated herpesvirus infection	15	1.71×10^-10
hsa05164	Influenza A	14	1.63×10^-9
hsa04668	TNF signaling pathway	14	3.04×10^-12
hsa05145	Toxoplasmosis	13	9.09×10^-11
hsa05152	Tuberculosis	13	2.27×10^-8
hsa04933	AGE-RAGE signaling pathway in diabetic complications	13	1.22×10^-11
hsa05145	To×oplasmosis	13	4.38×10^-11
hsa04657	IL-17 signaling pathway	12	9.42×10^-11
hsa05142	Chagas disease	11	1.37×10^-8
hsa04380	Osteoclast differentiation	11	1.26×10^-7
hsa04020	Calcium signaling pathway	11	2.30×10^-6
hsa05222	Small cell lung cancer	11	8.75×10^-10
hsa04022	cGMP-PKG signaling pathway	10	6.66×10^-6
hsa04024	cAMP signaling pathway	10	4.08×10^-5
hsa04620	Toll-like receptor signaling pathway	10	2.30×10^-7
hsa04261	Adrenergic signaling in cardiomyocytes	10	2.17×10^-6
hsa04151	PI3K-Akt signaling pathway	10	2.46×10^-5

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表 2 关键成分与相应核心靶点分子对接结果

Table 2. Docking results of key components with corresponding core target molecules

成分	靶点	Uniprot ID	PDB ID	结合能(kcal/mol)
kaempferol	RELA	Q04206	4KV4	-7.6
	STAT1	P42224	1BF5	-6.9
	MAPK8	P45983	4L7F	-6.5
ginsenoside rh2	IL1B	P01584	41BI	-6.7
	NFKBIA	P25963	6Y1J	-7.8
beta-sitosterol	JUN	P05412	1JNM	-7.6

下载: 导出CSV

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