Allicin Improves Diet-Induced Nonalcoholic Steatohepatitis and Gut Microbiota Dysbiosis in Mice via the Involvement of the Circadian Clock Gene Rev-erbα

Nonalcoholic Steatohepatitis (NASH) is a progressive liver disease characterized by inflammation and liver damage. Allicin, a bioactive compound derived from garlic, has demonstrated anti-inflammatory and antioxidant properties. This study explores the effects of allicin on NASH and gut microbiota dysbiosis induced by a high-fat, high-fructose diet (HFFD) in mice. Allicin supplementation significantly alleviated hepatic inflammation, improved glucose metabolism, and modulated the circadian rhythm gene Rev-erbα, which plays a critical role in regulating inflammation. The anti-inflammatory effects of allicin were diminished in Si-Rev-erbα-treated HepG2 cells, highlighting the importance of circadian regulation in mediating these effects. Allicin's anti-inflammatory effects were associated with increased levels of short-chain fatty acids (SCFAs) and the restoration of diurnal oscillations in proinflammatory cytokines and gut microbiota composition, particularly in genera, such as Akkermansia, Bacteroidetes, and Lactobacillus. These findings suggest that allicin could be a promising therapeutic approach for managing NASH, liver dysfunction, and related metabolic disorders through the modulation of circadian rhythms and the gut microbiome.