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

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

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 Gene Cards 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, PI3 K-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, PI3 K-Akt, and Jak-STAT signaling pathways. Moreover, it had the characteristics of multiple centers, multiple targets, and multiple pathways.

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Gene Cards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。