Hugan Tablets Alleviate Alcoholic Liver Injury by Modulating Hepatic Glutathione Metabolism and PPARγ/NRF2/GPX4-Related Antioxidant Defense

Background: Hugan tablets (HGP) are a commercially available traditional Chinese medicine preparation used for liver disorders, but the mechanisms underlying their effects on alcoholic liver injury (ALI) remain incompletely understood. This study investigated the hepatoprotective effects and potential mechanisms of HGP in ALI. Methods: An ALI mouse model was established using a Lieber–DeCarli ethanol liquid diet. The effects of HGP were evaluated using biochemical and histopathological assessments, followed by integrated liver and serum metabolomics, liver transcriptomics, and ELISA-based protein validation. Results: HGP alleviated alcohol-induced liver injury, hepatic lipid accumulation, oxidative stress, and inflammatory responses. Integrated multi-omics analyses indicated that HGP treatment was associated with changes in hepatic glutathione metabolism, PPAR signaling, and antioxidant-related processes. ELISA validation showed increased measured concentrations in liver homogenate supernatants of PPARγ, NRF2, GCL, and GPX4 following HGP treatment. These findings support the potential involvement of a PPARγ/NRF2/GPX4-related antioxidant network. Conclusions: HGP alleviated ALI in mice, and its effects may be associated with modulation of hepatic glutathione metabolism and a PPARγ/NRF2/GPX4-related antioxidant network. These findings provide experimental evidence for the potential use of HGP in alcohol-induced liver injury.