The defense role of luteolin-β-CD-MOF against acetaminophen induced liver toxicity by regulating of bile acids metabolism and gut microbiota.

Luteolin demonstrates hepatoprotective properties; however, its limited water solubility constrains its clinical applications. Luteolin-β-cyclodextrin metal-organic framework (Luteolin-β-CD-MOF) presents a more water-soluble alternative to luteolin. The precise mechanism by which luteolin-β-CD-MOF ameliorates liver injury through the modulation of gut microbiota has yet to be elucidated. Therefore, to evaluate the comprehensive effect of luteolin-β-CD-MOF on acetaminophen (APAP)-induced liver injury in rats, an integrated multi-omics approach was employed, encompassing bile acids (BAs) detection, gut microbiota sequencing analysis, and fecal metabolomics analysis. The findings revealed significant alterations in fecal BAs composition, gut microbiota structure, and fecal metabolite networks because of APAP overdose. Pathogenic bacteria, including Escherichia-Shigella, Helicobacter, and Oscillibacter were observed to proliferate; whereas beneficial bacteria, such as Christensenellaceae_R-7, Monoglobus, and Romboutsia were inhibited following APAP administration. Luteolin-β-CD-MOF was found to mitigate these changes and exhibited a more pronounced protective effect compared to raw luteolin. This study presents innovative insights into the hepatoprotective mechanisms of luteolin-β-CD-MOF and introduces a novel approach to disease prevention.