Exploring the Therapeutic Effects of Linarin on Ischemic Stroke: AnExperimental Assessment, Network Pharmacology, and MolecularDocking

Introduction: Linarin (LIN) is a flavone glycoside that has been reported to have analgesic, anti-inflammatory, and neuroprotective activities. This study aims to investigate the protective role of LIN against IS and explore its underlying mechanisms. Methods: The neuroprotective effect of LIN on CIRI was evaluated in the MCAO model mice through behavioral and pathological studies. Mechanistically, public databases were used to identify overlapping targets between LIN and IS. Then, the core genes were filtered by Cytoscape. The binding affinity between LIN and core targets was assessed by molecular docking simulations using AutoDock Vina. Additionally, GO and KEGG pathway enrichment analyses were conducted, and a “LIN-target-pathway” network was constructed. Finally, hub genes involved in LIN-mediated protection against IS were identified. Results: LIN has been confirmed to have a neuroprotective effect on MACO mice. Network pharmacology analysis suggests the effects are primarily associated with the PI3K/AKT and MAPK signaling pathways and core genes such as MAPK8. Six targets were considered central to how LIN exerts its protective role against CIRI as they are frequently involved in critical signaling pathways and exhibit strong binding affinity with LIN. Discussion: The therapeutic time window for mainstream IS treatment modalities remains narrow. This study, with a view to the preventive effect of Ischemic Stroke (IS), may provide novel insights into the management of IS. Conclusion: LIN has been shown to alleviate brain tissue damage in MCAO mice, potentially through modulation of multiple targets within the PI3K/AKT and MAPK signaling pathways, thereby exerting anti-inflammatory, anti-apoptotic, and neuroprotective effects.