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        <datestamp>2026-10-02T04:36:41Z</datestamp>
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          <dc:title>Supplementary file 1_Shenze shugan capsules alleviate alcoholic liver injury in association with modulation of the TGF-β/smad4 signaling pathway.docx</dc:title>
          <dc:creator>Lu Wang (45927)</dc:creator>
          <dc:creator>Qianyu Gu (25161291)</dc:creator>
          <dc:creator>Jia Tinghe (25161294)</dc:creator>
          <dc:creator>Zhen Sun (269397)</dc:creator>
          <dc:creator>Di Wang (329735)</dc:creator>
          <dc:creator>Lanzhou Li (4183957)</dc:creator>
          <dc:creator>Huiyun Zang (25161297)</dc:creator>
          <dc:creator>Lijun Lin (289688)</dc:creator>
          <dc:creator>Junliang Chen (1913437)</dc:creator>
          <dc:creator>Chunyue Wang (8933690)</dc:creator>
          <dc:subject>Pharmacology</dc:subject>
          <dc:subject>alcohol-associated liver disease</dc:subject>
          <dc:subject>fibrosis</dc:subject>
          <dc:subject>gut microbiota</dc:subject>
          <dc:subject>SZSG</dc:subject>
          <dc:subject>TGF-β/Smad4</dc:subject>
          <dc:description>Background&lt;p&gt;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.&lt;/p&gt;Methods&lt;p&gt;Both acute and chronic ALD mouse models were established to assess liver injury, fibrosis, inflammation, gut microbiota composition, and serum metabolomic profiles.&lt;/p&gt;Results&lt;p&gt;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.&lt;/p&gt;Conclusion&lt;p&gt;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.&lt;/p&gt;</dc:description>
          <dc:date>2026-10-02T04:36:41Z</dc:date>
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          <dc:identifier>10.3389/fphar.2026.1942947.s001</dc:identifier>
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          <dc:rights>CC BY 4.0</dc:rights>
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