Author Identifier (ORCID)
Wanqi Wang: https://orcid.org/0009-0006-3068-1080
Lois Balmer: https://orcid.org/0000-0001-5618-0555
Abstract
Background Intracranial aneurysm (IA) is a cerebrovascular disease with high mortality and limited treatment options. Tanshinone IIA (Tan IIA), a bioactive compound from Salvia miltiorrhiza , has shown vascular protective effects, but its mechanism in the treatment of IA remains unclear. Methods The GSE75436 dataset was used to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was performed to identify disease-related modules. IA targets were obtained from GeneCards and the Comparative Toxicogenomics Database (CTD). Potential targets of Tan IIA were predicted using TCMSP, SwissTargetPrediction, and SymMap. KEGG enrichment analysis was conducted for DEGs, WGCNA modules, disease-related genes, and Tan IIA target genes. A protein–protein interaction (PPI) network was constructed using STRING and analyzed by MCODE to identify hub genes. LASSO, SVM-RFE, and RF algorithms were used to screen key genes. GSEA was performed via SangerBox. Molecular docking was conducted with AutoDock Vina and visualized using PyMOL. Results A total of 1378 DEGs and 13 WGCNA modules were identified. KEGG analysis revealed 18 shared pathways among Tan IIA targets, IA-related genes, and WGCNA modules. Integration of drug targets yielded 53 candidate genes, of which 22 were identified as core genes by the MCODE algorithm. Four key genes ( CASP1 , TNF , CASP3 , JUN ) were selected by machine learning. GSEA indicated that these genes were closely associated with inflammation and immune pathways. Molecular docking results demonstrated strong binding affinity between Tan IIA and the core targets. Conclusion This study utilized network pharmacology and machine learning approaches to reveal that Tan IIA exerted therapeutic effects on IA by targeting multiple genes and pathways. Keywords Network pharmacology, Machine learning, Intracranial aneurysm, Tanshinone IIA, Molecular mechanism
Document Type
Journal Article
Date of Publication
1-1-2026
Publication Title
Letters in Drug Design & Discovery
Publisher
Elsevier
School
Centre for Precision Health / School of Medical and Health Sciences
RAS ID
88860
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
Wang, W., Balmer, L., & Weng, S. (2025). Exploring the mechanisms of tanshinone IIA in the treatment of intracranial aneurysm based on network pharmacology and machine learning. Letters in Drug Design & Discovery, 22(11), 100242. https://doi.org/10.1016/j.lddd.2025.100242