18β-Glycyrrhetinic acid ameliorates hepatic fibrosis through modulating bile acid profile and inhibiting TGF-β/SMAD3...

Oxidative stress drives the progression of liver disease from hepatitis to fibrosis, underscoring the need for dietary strategies to protect liver health. 18β-glycyrrhetinic acid (GA), a natural bioactive compound from Glycyrrhiza glabra, exhibits hepatoprotective, antioxidant, and anti-inflammatory properties. This study investigated the protective effects of dietary GA against D-galactose-induced hepatic injury in weaned piglets and explored its impact on hepatic function and gut-liver metabolism. The results showed that GA supplementation markedly reduced liver damage and fibrosis, as evidenced by histological improvements (H&E and Masson's staining), reduced hepatic AST activity, lower levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6), and decreased hydroxyproline content (P < 0.05). GA also modulated hepatic lipid metabolism by limiting stress-induced lipogenesis and activating PPARα, while concurrently suppressing TGF-β/SMAD3-mediated fibrotic signaling (P < 0.05). Multi-omics profiling revealed that GA restored bile acid homeostasis in the liver, serum, ileum, and colon, including normalization of conjugated and secondary bile acids, alleviating cholestasis and reinforcing gut-liver metabolic interactions (P < 0.05). These findings indicate that dietary GA can protect against oxidative stress-induced liver injury and fibrosis, potentially offering a dietary intervention strategy to maintain liver health and promote gut-liver metabolic balance.