Research on the Highly Efficient and Low-Dose Improvement of Alcohol-Induced Liver Injury by High-Selenium-Content...

There are currently no FDA-approved drugs for the treatment of alcohol-related liver diseases (ALD) due to their lack of effectiveness. Selenium-modified Lycium barbarum polysaccharides (SeLBP), as a promising agent for ALD, has not been studied before. In this study, with LBP and sodium selenite (Na₂SeO₃) as controls, and silymarin capsules, a clinical therapeutic agent, as a positive control, the therapeutic effects and mechanisms of SeLBP on ALD were systematically evaluated in an acute ALD mouse model. The results demonstrated that SeLBP, at the same dose, showed superior therapeutic effects on ALD compared to the use of LBP or Na₂SeO₃ alone, exhibiting a significant dose-response effect and significantly reversing alcohol-induced liver cell damage and inflammation (p < 0.05). Furthermore, 5.7 mg/kg BW of SeLBP demonstrated comparable efficacy to 50 mg/kg BW of silymarin (p > 0.05), highlighting a low-dose advantage. Mechanistic studies revealed that SeLBP significantly enhanced the activities of ADH and ALDH (p < 0.05) and significantly inhibited the activity and expression levels of cytochrome P450 2E1 (CYP2E1) and NADPH oxidase (NOX) that produce reactive oxygen species (ROS) (p < 0.05), thereby reducing ROS generation and restoring redox homeostasis (p < 0.05). Additionally, SeLBP significantly decreased the elevated levels of TG, TC, MDA, AST, and ALT caused by alcohol, while enhancing the activities of GSH-Px and SOD (p < 0.05), highlighting SeLBP's significant functions in promoting the normal metabolism of ethanol and preventing lipid peroxidation and oxidative damage. This study provides new insights and evidence for the potential use of SeLBP in ALD treatment.