基于网络药理学和分子对接技术探讨附子汤治疗慢性心力衰竭的作用机制

doi:10.5246/jcps.2021.09.058

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (9): 705-715.DOI: 10.5246/jcps.2021.09.058

• 【研究论文】 • 下一篇

基于网络药理学和分子对接技术探讨附子汤治疗慢性心力衰竭的作用机制

高太祥, 赵峰, 石莉尧, 王瑞^*()

山西中医药大学中药与食品工程学院, 山西晋中 030619

收稿日期:2021-04-20 修回日期:2021-05-11 接受日期:2021-06-18 出版日期:2021-09-27 发布日期:2021-09-27
通讯作者: 王瑞
作者简介:
+ Tel.: +86-351-3179903, E-mail: wrgreentea@163.com
基金资助:
Shanxi Science and Technology Department (Grant No. 2015011103), Shanxi Science and Technology Department (Grant No. 201901D111343) and "Research and development of Shanxi medicinal tea" of Shanxi University of traditional Chinese Medicine (Grant No. 2020PY-YC-10).

Exploring the mechanism of Fu-Zi Decoction in treatment of chronic heart failure based on network pharmacology and molecular docking technology

Taixiang Gao, Feng Zhao, Liyao Shi, Rui Wang^*()

School of Traditional Chinese Materia Medical, Shanxi University of Traditional Chinese Medicine, Jinzhong 030619, China

Received:2021-04-20 Revised:2021-05-11 Accepted:2021-06-18 Online:2021-09-27 Published:2021-09-27
Contact: Rui Wang

摘要/Abstract

摘要：

采用网络药理学方法探讨附子汤治疗慢性心力衰竭的作用机制。首先利用SymMap数据库分析各味药的现代医学症状, 然后通过TCMSP、ETCM数据库和前期结果得到附子汤化学成分, 并结合STITCH、SwissTargetPrediction、TargetNET数据库及文献获得附子汤作用靶点。在DisGeNET、GEO和DrugBank数据库中获取治疗慢性心力衰竭的靶点, 筛选出与附子汤靶点共同部分构建PPI网络, 对PPI网络模块化分解分析其功能并进行KEGG通路富集分析。最后对关键靶点由SwissDock进行分子对接验证。结果收集到附子汤化学成分205个, 药物靶点551个, 疾病靶点521个。功能富集分析发现主要参与细胞凋亡负调控、氧化应激和G蛋白偶联受体调节等生物过程。KEGG富集发现主要涉及血流剪切应力与动脉粥样硬化、IL-17信号通路等。分子对接结果显示苯甲酰乌头原碱、乌头碱、新乌头碱、芍药苷、白术内酯III均与核心靶点CXCL8具有较强亲和力。提示附子汤可能通过血流剪切应力与动脉粥样硬化、IL-17信号通路等发挥负调控细胞凋亡、氧化应激等作用, 起到治疗慢性心力衰竭的疗效。

关键词: 附子汤, 慢性心力衰竭, 网络药理学, 分子对接

Abstract:

In the present study, we aimed to explore the mechanism of Fu-Zi Decoction in the treatment of chronic heart failure (CHF) using network pharmacology. SymMap database was used to analyze the modern medical (MM) symptoms of various medicines. The chemical components of Fu-Zi Decoction were obtained through TCMSP, ETCM database, and previous results. The targets of Fu-Zi Decoction were obtained through STITCH, SwissTargetPrediction, TargetNET database, and literature. The targets for the treatment of CHF were obtained from the DisGeNET, GEO, and DrugBank databases, and the common parts of the Fu-Zi Decoction targets were screened out to construct the PPI network. The PPI network was decomposed modularly, its functions were analyzed, and the KEGG pathway enrichment analysis was performed. The key target was verified by SwissDock for molecular docking. A total of 205 chemical components of Fu-Zi Decoction, 551 drug targets, and 521 disease targets were collected. Functional enrichment analysis revealed that it was mainly involved in biological processes, such as negative regulation of cell death, oxidative stress, and G protein-coupled receptor regulation. KEGG enrichment findings mainly involved fluid shear stress and atherosclerosis, IL-17 signaling pathway, and so on. The results of molecular docking showed that benzoylaconitine, aconitine, mesaconitine, paeoniflorin, and atractylodes III all had a strong affinity with the core target CXCL8, suggesting that Fu-Zi Decoction could negatively regulate cell apoptosis and oxidative stress through fluid shear stress and atherosclerosis, IL-17 signaling pathway, and so on. Collectively, our data showed that Fu-Zi Decoction had a good effect on the treatment of CHF.

Key words: Fu-Zi Decoction, Chronic heart failure, Network pharmacology, Molecular docking

Supporting:

高太祥, 赵峰, 石莉尧, 王瑞. 基于网络药理学和分子对接技术探讨附子汤治疗慢性心力衰竭的作用机制[J]. 中国药学(英文版), 2021, 30(9): 705-715.

Taixiang Gao, Feng Zhao, Liyao Shi, Rui Wang. Exploring the mechanism of Fu-Zi Decoction in treatment of chronic heart failure based on network pharmacology and molecular docking technology[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 705-715.

图/表 6

Table 1. Experiment, Chinese Pharmacopoeia, and literature supplemented ingredient information.

Figure 1. Venn diagram of Fu-Zi Decoction targets and CHF targets.

Figure 2. Module decomposition diagram of PPI network. (The modules are numbered from the largest to the smallest, 1–4, the main biological processes involved in each module are: 1. response to oxidative stress; 2. G protein-coupled receptor signaling pathway; 3. response to stress; 4. steroid metabolic process.)

Figure 3. Results of GO function enrichment analysis.

Figure 4. Results of KEGG pathway enrichment analysis.

Figure 5. Molecular docking diagram of each compound and CXCL8 (1 to 5 is benzoylaconine, aconitine, mesaconitine, paeoniflorin, and atractylenolide III, respectively).

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基于网络药理学和分子对接技术探讨附子汤治疗慢性心力衰竭的作用机制

Exploring the mechanism of Fu-Zi Decoction in treatment of chronic heart failure based on network pharmacology and molecular docking technology

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