School of pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.
First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China.
J Cell Mol Med. 2023 Nov;27(22):3514-3525. doi: 10.1111/jcmm.17932. Epub 2023 Aug 29.
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.
丹参是治疗心肌梗死（MI）的天然药物。然而，丹参治疗 MI 的靶点和机制尚不清楚。本研究利用中药系统药理学（TCMSP）数据库筛选化学组成，利用 UniProt 数据库预测相关靶点。疾病靶点从在线孟德尔遗传数据库和基因数据库中获得。利用 STRING 平台构建蛋白质-蛋白质相互作用网络，利用 Cytoscape_v3.8.1 软件制作药物-成分-基因符号-疾病网络图。利用 Metascape 数据库对药物-疾病重叠基因符号进行基因本体和京都基因与基因组百科全书（KEGG）富集分析。通过网络药理学鉴定的靶点进一步通过体外和体内实验进行验证。从 TCMSP 数据库中获得了 75 种丹参的活性成分，从基因数据库中获得了 370 种疾病靶点和 29 种交叉靶点。KEGG 通路富集结果表明，丹参治疗 MI 的机制与 VEGF 信号通路显著相关。体外和体内实验评估了一些重要活性成分和靶点的可靠性。丹参通过增加 TGF-β和 VEGFA 的表达，减轻心脏功能损伤，减轻心肌纤维化，保护内皮细胞功能，从而发挥治疗 MI 的作用。丹参通过促进 VEGFA 信号通路的表达发挥 MI 的治疗作用，为探索中药治疗 MI 提供了可靠的依据。
