Integrated network pharmacology to investigate the mechanism of Salvia miltiorrhiza Bunge in the treatment of myocardial infarction.

Integrated network pharmacology to investigate the mechanism of Salvia miltiorrhiza Bunge in the treatment of myocardial infarction.
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DOI:
10.1111/jcmm.17932
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发表时间:
2023-11
影响因子:
5.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
作者:

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丹参是一种治疗心肌梗死的天然药物。然而,丹参治疗心肌梗死的靶点和机制尚不清楚。利用中药系统药理学(TCMSP)数据筛选化学成分,利用UniProt预测相关靶点。疾病靶标从人类在线孟德尔遗传和GeneCards数据库获得。我们使用STRING平台构建了蛋白质-蛋白质相互作用网络,并使用Cytoscape_v3.8.1软件制作了药物-成分-基因符号-疾病网络图。使用Metascape数据库进行基因本体和京都基因和基因组百科全书(KEGG)富集分析,以获得药物-疾病重叠基因符号。通过体内外实验进一步验证了网络药理学所确定的靶点。从TCMSP数据库中获得了75种丹参活性成分,从Genecards数据库中获得了370个疾病靶标和29个交叉靶标。KEGG信号通路富集结果提示丹参治疗心肌梗死的机制与VEGF信号通路密切相关。采用体内外实验对一些重要活性成分和作用靶点进行了可靠性评价。丹参通过增加TGF-β和VEGFA的表达,减轻心功能损害,减轻心肌纤维化,保护内皮细胞功能。丹参通过促进VEGFA信号通路的表达发挥治疗心肌梗死的作用,为探讨中药治疗心肌梗死提供了可靠依据。
Salvia miltiorrhiza Bunge is a natural drug for treating myocardial infarction (MI). However, the targets and mechanisms of S. miltiorrhiza Bunge in the treatment of MI are yet to be elucidated. Traditional Chinese medicine systems pharmacology (TCMSP) data were used to screen out chemical constituents, and UniProt was used to predict relevant targets. Disease targets were obtained from the Online Mendelian Inheritance in Man and GeneCards databases. We used the STRING platform to build a protein–protein interaction network and used Cytoscape_v3.8.1 software to make a Drug–Ingredients–Gene Symbols–Disease network map. The Metascape database was used to perform gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses for drug–disease overlapping gene symbols. The targets identified by network pharmacology were further verified by in vitro and in vivo experiments. Seventy‐five active components of S. miltiorrhiza Bunge were obtained from the TCMSP database, while 370 disease targets and 29 cross‐targets were obtained from the Genecards database. The KEGG pathway enrichment results suggested that the mechanism of S. miltiorrhiza Bunge in the treatment of MI was significantly related to the VEGF signalling pathway. In vitro and in vivo experiments were used to evaluate the reliability of some important active ingredients and targets. S. miltiorrhiza Bunge alleviated the damage to cardiac function, attenuated myocardial fibrosis and protected endothelial cell function by increasing the expression of TGF‐β and VEGFA. S. miltiorrhiza Bunge showed the therapeutic effect of MI by promoting the expression of VEGFA signalling pathway, providing a reliable basis for exploring herbal treatment of MI.
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