Min Zhao,1 Liuxiang Feng,2 Wenhua Li3 

1School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China; 2People’s Hospital of Yulong Naxi Autonomous County of Lijiang City, Lijiang, Yunnan, 674112, People’s Republic of China; 3School of Medicine, Xizang Minzu University, Xianyang Shaanxi, 712082, People’s Republic of China

Correspondence: Min Zhao, School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China, Email 1398606492@qq.com

Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

Keywords: SQDS, cardiac troponin I, PI3K/AKT signaling pathway, coronary heart disease, experiment validation