Allicin-free garlic extract alleviates alcohol-induced liver injury in mice by reducing oxidative stress through activation of PPARγ

Garlic (Allium sativum L.) is well known for its antioxidant activity and has been demonstrated to protect against alcoholic liver disease (ALD); however, its pungent odor hinders its broader application. This study introduced allicin-free garlic extract (AFGE), and investigated its effect on alcohol-induced hepatotoxicity and the underlying mechanisms. ICR mice were administered AFGE at doses of 0.5, 1, and 2 g/kg for 30 days, followed by a single dose of alcohol (14 mL/kg) to simulate human binge drinking. AFGE significantly alleviated alcohol-induced hepatocellular injury, reduced hepatic lipid accumulation and oxidative damage. These antioxidant beneficial effects were further confirmed in aged mice, as evidenced by decreased hepatic levels of malondialdehyde and protein carbonyls, and increased levels of glutathione and catalase. Transcriptomic analysis and integrated bioinformatic analysis identified Gpx3, Gsto2, and Gsta1 as core antioxidant genes involved in the protective effects against alcohol-induced hepatotoxicity. Further analysis with Cytoscape revealed that peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcription factor regulating the expression of these genes. Indeed, the hepatic abundance of PPARγ was markedly upregulated by AFGE compared with the alcohol group, indicating the involvement of this transcription factor in the protective effects of AFGE. In addition, molecular docking and western blotting showed that alliin, one of the main components of AFGE, directly binds to and activates PPARγ. Collectively, these findings demonstrate that AFGE mitigates alcohol-induced liver injury by activating PPARγ-mediated transcription of antioxidant genes, supporting its potential as a functional food for the prevention and management of ALD.