Protective mechanism of moslosooflavone against hypobaric hypoxia-induced brain injury: insights from network pharmacology and in vivo validation.

Moslosooflavone, which is a natural flavonoid, demonstrates significant protective effects against hypobaric hypoxia-induced brain injury (HHBI). Nevertheless, its underlying mechanisms are still poorly understood. The present study aimed to elucidate the neuroprotective mechanisms of moslosooflavone against HHBI by integrating network pharmacology with in vivo experimental validation. Potential targets of moslosooflavone and HHBI-related genes were retrieved from public databases. The STRING database in conjunction with Cytoscape 3.9.1 software was used to construct a comprehensive protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed via the DAVID database to screen key signaling pathways. Molecular docking was conducted via AutoDock Vina to validate the interactions. In vivo experiments confirmed the protective mechanism of moslosooflavone. A total of 78 common targets were identified, with ALB, AKT AKT1, HIF1A, ESR, and HSP90AA being identified as core targets. The PI3K/AKT signaling pathway was identified as a primary pathway via GO and KEGG enrichment analysis. Molecular docking revealed strong binding affinity between moslosooflavone and both PI3K and AKT1. In vivo studies indicated that moslosooflavone upregulated p-PI3K and p-AKT protein levels in the brain tissues of mice exposed to HH. However, this effect was reversed by the PI3K/AKT inhibitor known as LY294002. Additionally, the beneficial effects of moslosooflavone, including reducing pathological damage and exerting antioxidant, anti-inflammatory, and antiapoptotic effects, were significantly attenuated by LY294002. These findings suggest that the modulation of the PI3K/AKT signaling pathway is a key mechanism underlying the protective effects of moslosooflavone against HHBI.