Ginkgo Biloba Extract Alleviates AFB1-Induced Hepatic Lipid Metabolism Disorder and Apoptosis in Mice: Associated with Modulation of the PI3K/AKT/FOXO1 Signaling Pathway

Aflatoxin B1 (AFB1) is the most toxic aflatoxin, posing a persistent threat to food safety and animal husbandry. Ginkgo biloba extract (GBE) is a bioactive herbal extract with well-recognized antioxidant, anti-inflammatory, and lipid-regulating activities. However, its protective mechanisms against AFB1-induced hepatotoxicity remain incompletely clarified. This study integrated network pharmacology, network toxicology, molecular docking, and in vivo experiments in mice to explore the hepatoprotective effects of GBE and revealed its underlying regulatory pathways. The PI3K/AKT, FOXO, lipid and atherosclerosis, and apoptosis pathways were considered the associated mechanisms that mediated the protective effects of GBE against AFB1-induced hepatotoxicity. Molecular docking predicted that the main active components of GBE could stably bind to PI3K, AKT1, Srebp-1, FASN, Bcl-2, and Caspase-3. Furthermore, GBE significantly decreased serum AST, ALT, and GLB levels, enhanced hepatic T-SOD and GSH-Px activities, reduced ROS, LPO, and MDA accumulation, and reduced histopathological damage in the liver of AFB1-exposed mice. GBE also upregulated the expression of PI3K, AKT, PPAR-γ, LXR-α, Scarb-1, and LDLR, but downregulated FOXO1, Srebp-1, FASN, and Acc-1 in AFB1-exposed mice, thereby alleviating hepatic lipid metabolism disorder. Finally, GBE significantly elevated Bcl-2 expression and the Bcl-2/Bax ratio, decreased Bax, Caspase-9, and Caspase-3 levels, and alleviated AFB1-induced hepatocyte apoptosis. Collectively, the protective effect of GBE against AFB1-induced hepatic dysfunction, oxidative damage, lipid metabolic disorder, and apoptosis was closely associated with modulation of the PI3K/AKT/FOXO1 pathway. These findings provide a theoretical foundation for the development of GBE as a candidate for further research into AFB1-induced hepatotoxicity.