Effect and Mechanism of Tauroursodeoxycholic Acid in Blue Fox Bile on Acute Alcohol-Associated Liver Injury in Mice

Animal bile, such as bear bile, have long been used in traditional medicine for its therapeutic benefits. Blue fox bile, similar to bear bile, is believed in certain traditional practices to possess hepatoprotective properties. This study examined the components and effects of blue fox bile on alcohol-associated liver injury in mice. Bile was collected from 30 blue foxes and processed into dried powder. The chemical composition of blue fox bile was analyzed using high-performance liquid chromatography and ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Network pharmacology was employed to identify potential bioactive compounds, targets, and pathways associated with alcohol-associated liver injury. A mouse model of alcohol-associated liver injury was established using Kunming mice, which were administered blue fox bile powder at low and high doses. Serum alanine aminotransferase, aspartate aminotransferase, and total cholesterol levels were measured. Liver tissues were assessed by hematoxylin and eosin staining and malondialdehyde assay. Molecular docking was performed to predict the binding affinity between active compounds and core targets. Blue fox bile was found to contain tauroursodeoxycholic acid (TUDCA), ursodeoxycholic acid, bilirubin, and taurochenodeoxycholic acid. Histopathological analysis revealed no significant abnormalities or toxic effects in major organs following oral administration of blue fox bile powder. The core targets of blue fox bile included protein AKT1, PPARG, IGF1, MMP9, andCASP3. Blue fox bile treatment decreased serum ALT, AST, cholesterol, and MDA levels in mouse models of alcohol-related liver injury. Network pharmacology and molecular docking suggest that the hepatoprotective effects of blue fox bile may be related to the advanced glycation end product-receptor for advanced glycation end product signaling pathway. Overall, blue fox bile, with its TUDCA content similar to that of bear bile, targets proteins such as AKT1 and PPARG, demonstrating potential anti-inflammatory and antioxidant effects in the management of alcohol-associated liver injury.