Shenze shugan capsules alleviate alcoholic liver injury in association with modulation of the TGF-β/smad4 signaling pathway

Abstract

Alcohol-associated liver disease (ALD) represents a major contributor to liver fibrosis globally, and current therapeutic options remain inadequate. The TGF-β/Smad4 cascade is critically involved in alcohol-evoked activation of hepatic stellate cells and subsequent extracellular matrix accumulation. Although Shenze Shugan capsule (SZSG) has been clinically used for non-alcoholic steatohepatitis, its efficacy and mechanisms in ALD are unclear. This study aimed to explore how SZSG exerts protective effects against alcohol-triggered liver injury and the underlying mechanisms. Both acute and chronic ALD mouse models were established to assess liver injury, fibrosis, inflammation, gut microbiota composition, and serum metabolomic profiles. SZSG treatment markedly attenuated hepatic steatosis, fibrosis, and inflammation, as evidenced by reductions in lipid accumulation, collagen deposition, and pro-inflammatory cytokine levels. Concurrently, it reshaped the gut microbiota and restored metabolites dysregulated by alcohol exposure. These beneficial effects appear to involve modulation of the TGF-β/Smad4 signaling pathway and its downstream effectors, α-SMA and Collagen I. Collectively, our findings suggest that SZSG combats ALD by simultaneously modulating the TGF-β/Smad4 signaling axis and preserving gut-liver homeostasis, thereby representing a promising multi-target therapeutic candidate.