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

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 <i>Rev-erbα,</i> which plays a critical role in regulating inflammation. The anti-inflammatory effects of allicin were diminished in Si-<i>Rev-erbα</i>-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 <i>Akkermansia</i>, <i>Bacteroidetes</i>, and <i>Lactobacillus</i>. 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.