Elucidating the mechanism of ferulic acid in treating ischemic stroke based on network pharmacology and multi-omics analysis

Ischemic stroke, the prevalent cerebrovascular disease, has high morbidity and mortality. Ferulic acid, a phenolic compound, has antioxidant, antibacterial, and neuroprotective effects. This study explores its mechanisms in alleviating ischemic stroke. Genes associated with ischemic stroke were screened using GeneCards. Potential targets of ferulic acid were predicted through SwissTargetPrediction, TargetNET, and SuperPRED. A PPI network was constructed for the overlapping targets on the STRING database to identify hub genes. GO and KEGG enrichment analyses of key genes were performed using DAVID. AutoDock Vina simulated ferulic acid’s interactions with key targets. The GSE16561 dataset was analyzed using Sangerbox to identify differentially expressed genes. The PXD036840 dataset from EMBL was also analyzed using Sangerbox to identify differentially expressed proteins, followed by PCA using ggplot2. Network pharmacology analysis identified SRC, AKT1, PIK3R1, PIK3CA, and STAT3 as the core therapeutic targets of ferulic acid for treating ischemic stroke. Molecular docking studies further validated that ferulic acid could bind stably to these targets. Combined transcriptomic and proteomic analyses revealed that targets such as LAMP2, F13A1, ORM1, HP, LRG1, and CD14 might play crucial roles in the pathogenesis of ischemic stroke. Moreover, immune responses, inflammatory reactions, cell apoptosis, and associated signaling pathways are crucial in ischemic stroke mechanisms, potentially serving as key targets for ferulic acid's pharmacological actions. Ferulic acid may alleviate ischemic stroke via multiple targets and regulating multiple pathways. This offers fresh insights and potential drugs for clinical treatment. • SRC, AKT1, PIK3R1, PIK3CA and STAT3 are the core targets of ferulic acid for mitigating ischemic stroke. • Ferulic acid can stably bind to SRC, AKT1, PIK3R1, PIK3CA, and STAT3. • LAMP2, F13A1, ORM1, HP, LRG1, and CD14 are crucial for ischemic stroke pathogenesis. • Ferulic acid may mitigate inflammation and cell apoptosis from ischemic stroke via inhibiting key pathways like NF-κB.