Network pharmacology and experimental validation reveal dexmedetomidine’s protective mechanisms against acute liver injury in mice

This study explored the role and molecular mechanisms of dexmedetomidine (DEX), an α2-adrenergic receptor agonist, in the treatment of a mouse model of acute liver injury (ALI). DEX significantly mitigated hepatic tissue damage and reduced serum levels of liver function biomarkers and proinflammatory cytokines. Network pharmacology analysis revealed 81 common targets between DEX and ALI, identifying 10 crucial hub genes. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that DEX's therapeutic effect on ALI is likely linked to the activation of the PI3K/AKT pathway. Immunohistochemical experiments verified DEX's activation of the PI3K/AKT pathway. Molecular docking and dynamic simulations confirmed the stable interaction between DEX and the epidermal growth factor receptor (EGFR). Immunohistochemistry and western blotting further validated that DEX pretreatment upregulated EGFR expression. Our findings indicate that DEX may mitigate ALI by interacting with EGFR and triggering the PI3K/AKT pathway. These findings provide a solid theoretical and experimental basis for using DEX as a potential therapeutic regimen for treating inflammatory liver diseases.