基于网络药理学方法探讨丹参治疗病理性瘢痕的作用机制

doi:10.5246/jcps.2021.10.069

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (10): 813-821.DOI: 10.5246/jcps.2021.10.069

基于网络药理学方法探讨丹参治疗病理性瘢痕的作用机制

张洪壮¹^,²^,^#, 杨智伟¹^,^#, 张江河¹^,^#, 张一鸣¹, 侯世科², 王振国², 闫利²^,^*(), 樊东力¹^,^*()

1. 陆军军医大学第二附属医院, 重庆 400037
2. 武警特色医学中心, 天津 300162

收稿日期:2021-04-18 修回日期:2021-05-20 接受日期:2021-06-19 出版日期:2021-10-24 发布日期:2021-10-24
通讯作者: 闫利, 樊东力
作者简介:
+ Tel.: +86-13508333033, E-mail: dlfan4612@163.com
+ Tel.: +86-13502071696, E-mail: yyyanli1234@126.com
基金资助:
The National Key Research and Development Projects (Grant No. 2017YFC1307602); the Scientific Research Projects of Tianjin (Grant No. 16ZXHLSY00120; 15ZXLCSY00040); Logistics College of PAP Projects (Grant No. WHJ201729); Logistics Project of PAP (Grant No. CWJ18L004).

Discussion on the mechanism of Salvia miltiorrhiza in treating pathological scars based on network pharmacology

Hongzhuang Zhang¹^,²^,^#, Zhiwei Yang¹^,^#, Jianghe Zhang¹^,^#, Yiming Zhang¹, Shike Hou², Zhenguo Wang², Li Yan²^,^*(), Dongli Fan¹^,^*()

1 The Second Affiliated Hospital of Army Military Medical University, Chongqing 400037, China
2 Featured Medical Center of Chinese People's Armed Police Forces, Tianjin 300162, China

Received:2021-04-18 Revised:2021-05-20 Accepted:2021-06-19 Online:2021-10-24 Published:2021-10-24
Contact: Li Yan, Dongli Fan
About author:
# Hongzhuang Zhang, Zhiwei Yang and Jianghe Zhang contributed equally to this work.

摘要/Abstract

摘要：

本研究通过网络药理学方法, 探讨丹参治疗病理性瘢痕(pathological scar, PS)的作用机制。通过TCMSP数据库筛选丹参的活性成分和药物靶点, 在GeneCards数据库获取PS的疾病靶点, 对药物靶点和疾病靶点进行韦恩图分析, 取交集为丹参治疗PS的作用靶点。利用Cytoscape软件构建药物-成分-靶点-疾病网络图。通过String网站构建蛋白质互作网络, 用Cytoscape软件筛选其关键蛋白模块及Hub基因, DAVID数据库进行GO和KEGG富集分析。筛选得到59个活性成分, 138个药物靶点, 90个丹参治疗PS的作用靶点; 得到木犀草素、丹参酮IIA等核心成分; 筛选出VEGFA、TP53、JUN、STAT3、AKT1、MAPK1、PTGS2等Hub基因以及HIF-1、TNF、MAPK、PI3K-Akt、Jak-STAT等信号通路。可以得出, 丹参可通过调控HIF-1、TNF、MAPK、PI3K-Akt、Jak-STAT等信号通路, 改善PS缺氧状态、炎症反应及成纤维细胞增值与凋亡平衡, 具有多中心、多靶点、多途径的特点。

关键词: 病理性瘢痕, 网络药理学, 丹参

Abstract:

In the present study, we aimed to explore the mechanism of Salvia miltiorrhiza in the treatment of pathological scars (PS) by network pharmacology. The active ingredients and drug targets of Salvia miltiorrhiza were screened out through TCMSP database, the disease targets of PS in GeneCards database were obtained, and Venn diagram analysis on drug targets and disease targets was performed, and the intersection was used as the target of Salvia miltiorrhiza for the treatment of PS. Cytoscape software was used to construct a drug-ingredient-target-disease network diagram. A protein-protein interaction network was constructed through String website, its key protein modules and hub genes were screened with Cytoscape software, and GO and KEGG enrichment analyses were performed in DAVID database. Fifty-nine active ingredients, 138 drug targets, and 90 targets of Salvia miltiorrhiza for the treatment of PS were screened out. Core ingredients, such as luteolin and tanshinone IIA, were obtained. The hub genes, such as VEGFA, TP53, JUN, STAT3, AKT1, MAPK1, and PTGS2, and signaling pathways, such as HIF-1, TNF, MAPK, PI3K-Akt, and Jak-STAT, were screened out. Salvia miltiorrhiza might improve PS hypoxia, inflammation, and balance of proliferation and apoptosis of fibroblasts by regulating HIF-1, TNF, MAPK, PI3K-Akt, and Jak-STAT signaling pathways. Moreover, it had the characteristics of multiple centers, multiple targets, and multiple pathways.

Key words: Pathological scar, Network pharmacology, Salvia miltiorrhiza

Supporting:

张洪壮, 杨智伟, 张江河, 张一鸣, 侯世科, 王振国, 闫利, 樊东力. 基于网络药理学方法探讨丹参治疗病理性瘢痕的作用机制[J]. 中国药学(英文版), 2021, 30(10): 813-821.

Hongzhuang Zhang, Zhiwei Yang, Jianghe Zhang, Yiming Zhang, Shike Hou, Zhenguo Wang, Li Yan, Dongli Fan. Discussion on the mechanism of Salvia miltiorrhiza in treating pathological scars based on network pharmacology[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(10): 813-821.

图/表 5

Figure 1. The Venn diagram of the target of Salvia miltiorrhiza and the target of pathological scar.

Figure 2. Drug-ingredient-target-disease network of Salvia miltiorrhiza for pathological scar treatment. The yellow node: the active ingredient of Salvia miltiorrhiza, the first letter of Salvia miltiorrhiza plus Arabic numerals; green node: the gene target of Salvia miltiorrhiza in the treatment of pathological scar. The larger the node, the higher the degree value, indicating that the node is more important. PS, pathological scar.

Table 1. The active ingredients and molecular names of Salvia miltiorrhiza in the treatment of PS (top 10 degree scores).

Figure 3. PPI network diagram, key modules, and hub genes of Salvia miltiorrhiza in the treatment of PS. The larger the node and the darker the color, the more important the node. (A) PPI network of PS targets treated with Salvia miltiorrhiza; (B) PPI network protein key module; (C) Hub genes of key modules.

Figure 4. Analysis of key module gene function enrichment. (A) Key module gene GO analysis map; (B) Bubble chart of key module gene KEGG enrichment.

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基于网络药理学方法探讨丹参治疗病理性瘢痕的作用机制

Discussion on the mechanism of Salvia miltiorrhiza in treating pathological scars based on network pharmacology

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