Luteolin-β-CD-MOF prevents against acetaminophen-mediated liver damage by controlling ferroptosis through GSH/GPX4/SLC7A11 signal axis

Excess acetaminophen can result in hepatotoxicity, while luteolin has the anti-liver injury property. However, the low water solubility reduces its pharmacological performance. Luteolin-β-Cyclodextrin-Metal-Organic-Framework (Luteolin-β-CD-MOF) is an alternative with more water-soluble activity of luteolin. In this study, we utilized in vivo and in vitro methods to explore the underlying protective mechanism of luteolin-β-CD-MOF in acetaminophen-induced liver injury. Untargeted metabolomics were performed, along with the study of bile acids metabolism in liver injured rats. Western blotting assays were performed to assess the expressions of ferroptosis-related proteins (glutathione peroxidase 4 (GPX4), ferritin heavy chain-1 (FTH1), heme oxygenase-1 (HO-1), and solute carrier family 7 member 11 (SLC7A11)) in rats and L02 cells. The findings demonstrated that the intervention with luteolin-β-CD-MOF ameliorated the acetaminophen-induced liver injury and restored dysregulated bile acids metabolism by mitigating the acetaminophen-induced ferroptosis through GSH/GPX4/SLC7A11 signal axis. This research offers novel perspectives on acetaminophen-liver injury prevention strategies.