Dan Wang,1– 3 Qipeng Jin,1– 3 Jianwei Zhang,4 Xuefei Shi,1– 3 Xiaolong Wang1– 3 

1Cardiovascular Research Institute of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Cardiovascular Department of Traditional Chinese Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Branch of National Clinical Research Center for Chinese Medicine Cardiology, Shanghai, People’s Republic of China; 4Department of pharmacy, The NATCM Third Grade Laboratory of Traditional Chinese Medicine Preparations, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

Correspondence: Xiaolong Wang, Fax +86 21 51322445, Email wxlqy0214@163.com

Background: Dunyeguanxinning (DYGXN) has been shown to have therapeutic effects in preventing and treating atherosclerosis. However, the active components and anti- atherosclerosis (AS) mechanisms of DYGXN remain to be elucidated.
Purpose: This study aims to explore the functional mechanisms of Dunyeguanxinning (DYGXN) in the prevention and treatment of atherosclerosis (AS).
Methods: The components of DYGXN were identified using UPLC-Q-Orbitrap HRMS technology. Network pharmacology and molecular docking were utilized to explore the functional mechanisms and core targets of DYGXN. An AS mouse model was established to verify the results obtained from network pharmacology.
Results: A total of 20 compounds were identified or tentatively characterized in the DYGXN solution. In total, 149 potential targets of DYGXN and 4,071 AS-related targets were obtained, with 92 overlapping targets between DYGXN and AS. The protein–protein interaction (PPI) network analysis identified 10 key targets, including SRC and STAT3, along with four core subnetworks. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis indicated that these targets were primarily involved in processes such as phosphorylation, positive regulation of cell migration, inflammatory response and pathways such as lipid and atherosclerosis. Molecular docking demonstrated strong binding affinities between DYGXN compounds and core targets. In vivo experiments showed that DYGXN improved blood lipid levels, reduced pro-inflammatory cytokines, downregulated phosphorylation of Src and STAT3, alleviated hepatic lipid accumulation, and inhibited plaque formation in AS model mice.
Conclusion: DYGXN contains multiple saponins that exert anti-AS effects through the regulation of multiple targets and pathways.

Keywords: Dunyeguanxinning, network pharmacology, atherosclerosis, UPLC-Q-orbitrap HRMS, molecular docking