Revealing the Mechanism and Therapeutic Target of Dengshi Wendan Decoction on Atherosclerosis Based on Network Pharmacology

FANG Junfeng; LIU Shiyi; WU Wei

doi:10.12102/j.issn.1672-1349.2025.03.003

Abstract：Objective:To examine the potential molecular mechanism and therapeutic target of Dengshi Wendan Decoction(DSWD)for the treatment of atherosclerosis(AS)based on network pharmacology,molecular docking,and experimental verification.Methods:Active ingredients and corresponding targets in DSWD were obtained from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP).GSE28829 and GSE43292 were downloaded to identify the differential expressed genes(DEGs)of early and advanced atherosclerotic plaques,then enrichment analyses were performed on DEGs.The optimal candidate genes of AS were identified by several bioinformatics algorithms,which intersected with DSWD-related targets to determine the essential treatment targets.Ultimately,the hub targets were validated by molecular docking and vivo experiments.Results:A total of 190 compounds and 261 corresponding targets were screened out,and 81 DEGs were identified,then the matrix metalloproteinase 9(MMP9)was intersected as the hub target for DSWD against AS.Additionally,MMP9 showed a significantly higher expression level in the AS group with promising diagnostic value,and five key active compounds reliably and firmly binded with MMP9.In vivo,DSWD could alleviate high fat diet-induced histopathological lesions by inhibiting plaque formation,reducing foam cell deposition and collagen fiber content in apolipoprotein E knockout(ApoE-/-)mice.Immunohistochemistry indicated that Dengshi Wendan decoction significantly suppressed the expression of MMP9.Conclusion:DSWD could treat AS through the synergistic interplay of various active components,therapeutic targets,and signaling pathways,and MMP9 may serve as a valuable biomarker and therapeutic target.