Identification of diagnostic biomarkers for ischemic stroke and drug targets of Buyang Huanwu decoction: A bioinformatics and network pharmacology study
Shun Fu, Wensheng Tang, Shisui Luo, W. Wang, Yin Huang, Hao Li, Guixue Wang
Abstract
Buyang Huanwu decoction (BHD) is extensively employed in the management of ischemic stroke (IS), yet its drug targets and mechanisms of action in IS remain obscure. Thus, in this investigation, network pharmacology and computational biology techniques were employed to investigate the drug targets of BHD in the management of IS. This study aims to identify diagnostic biomarkers for IS and to elucidate the potential drug target network of BHD using integrated bioinformatics and network pharmacology approaches. mRNA expression profiles (GSE16561, GSE58294) were retrieved from the Gene Expression Omnibus (GEO). BHD compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database (oral bioavailability ≥ 30 %, drug-likeness ≥ 0.18). Predicted compound targets (SwissTargetPrediction) were mapped to UniProt IDs. Differentially expressed genes were identified with limma (|log_2 FC| > 0.5, adjusted P < .05). Key coexpression modules were extracted by weighted gene coexpression network analysis (WGCNA; |cor| ≥ 0.4). Intersecting differentially expressed genes, WGCNA genes, and compound targets yielded candidate genes, refined by LASSO regression. Functional enrichment (Gene Ontology/Kyoto Encyclopedia of Genes and Genomes), gene set enrichment analysis, protein-protein interaction (STRING), and regulatory network analysis (miRDB, JASPAR) were performed. Diagnostic value was evaluated by receiver operating characteristic curves; a nomogram was constructed and calibrated. The analysis revealed several key targets of BHD that are potentially involved in the treatment of IS, including ARG1, CYP1B1, PAK1, and PYGL. These targets were enriched in pathways related to neuroprotection and anti-inflammatory responses, suggesting that BHD may exert therapeutic effects through these mechanisms. This study provides insights into the molecular targets and pathways through which BHD may alleviate IS, providing a foundation for future experimental validation and potential therapeutic strategies for stroke management.