Emodin Alleviates Alcohol-Induced Liver Fibrosis by Modulating Extracellular Matrix and Inhibiting the TGF-β1/Smad3 Signaling Pathway

Objective: The natural anthraquinone emodin exhibits multiple pharmacological effects, including anti-inflammatory and anti-fibrotic properties. However, its therapeutic potential and mechanism of action in alcoholic liver fibrosis (ALF) remain insufficiently explored. Methods: The therapeutic effect of emodin was evaluated in a mouse model of ALF induced by chronic ethanol feeding and in ethanol-exposed hepatic stellate cells (HSC-T6) in vitro. Serum biochemistry, liver histopathology, and the expression of fibrosis-related markers were assessed. Results and Discussion: In vitro, emodin dose-dependently inhibited the proliferation and promoted the apoptosis of ethanol-exposed HSC-T6 cells. In vivo, emodin treatment significantly reduced serum ALT and AST levels, attenuated histopathological damage, and decreased collagen deposition in ALF mice. Molecular analyses revealed that emodin downregulated miR-21 expression and upregulated the expression of its target, ADAMTS-1. Emodin treatment also inhibited the TGF-β1/Smad3 signaling pathway and shifted the balance of extracellular matrix regulators by decreasing TIMP-1 and increasing MMP-2 expression in both models. Conclusions: Emodin demonstrates potent anti-fibrotic effects in experimental ALF. Its mechanism is associated with the inhibition of the TGF-β1/Smad3 pathway, modulation of the miR-21/ADAMTS-1 axis, and restoration of the MMP-2/TIMP-1 balance, leading to enhanced matrix degradation. These findings highlight emodin as a promising candidate for further investigation in the treatment of alcoholic liver fibrosis.