School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People's Republic of China.
People's Hospital of Yulong Naxi Autonomous County of Lijiang City, Lijiang, Yunnan, 674112, People's Republic of China.
Drug Des Devel Ther. 2024 Oct 9;18:4529-4550. doi: 10.2147/DDDT.S480248. eCollection 2024.
To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease.
We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin.
Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue.
Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.
运用网络药理学预测三七丹参（SQDS）治疗冠心病的成分和通路，然后通过体外实验验证 SQDS 治疗冠心病的分子机制。
我们从中药系统药理学数据库中获取三七和丹参的活性成分和靶点。从 OMIM、Genecards 和 Therapeutic Target 数据库中检索冠心病相关基因。使用 Cytoscape 3.7.2 软件构建 SQDS 成分和靶点的网络图。将相关靶点导入 STRING 数据库构建蛋白质-蛋白质相互作用网络。利用 Metascape 数据库和微信软件进行基因本体和京都基因与基因组百科全书富集分析。最后，我们使用 AutoDock Vina 对关键成分和相关靶点进行分子对接。为了验证 SQDS 治疗冠心病的潜在机制，我们通过尾静脉注射垂体后叶素建立急性冠心病大鼠模型。
网络药理学分析表明，SQDS 治疗冠心病涉及 65 种活性成分和 167 个靶点。鉴定的关键靶点包括 AKT1、TNF、TP53、IL6 和 VEGFA。值得注意的是，PI3K/AKT 信号通路是主要通路。此外，动物实验表明，与模型组相比，SQDS 能显著降低 TNF-α、IL-6、Bax 和心肌肌钙蛋白 I 的水平，同时增加 Bcl-2 含量。它还显著抑制了 p-PI3K 和 p-AKT 的表达，从而对心肌组织起到保护作用。
通过网络药理学和分子对接的综合方法，我们建立了 SQDS 对冠心病具有多成分、多靶点、多途径协同治疗作用的假说。其机制可能涉及抑制 PI3K/AKT 信号通路和降低炎症因子表达。
