Smilax china L. Extract Alleviates Metabolic-Associated Fatty Liver Disease by Regulating Gut Microbiota and Bile Acid Metabolism

<b>Background:</b> Metabolic-associated fatty liver disease (MAFLD) is prevalent in individuals with liver disease; however, it lacks effective therapeutic approaches. <i>Smilax china</i> L., a traditional Chinese medicinal herb, possesses excellent anti-inflammatory and antioxidant activity. This research aimed to explore the therapeutic effects of <i>Smilax china</i> L. extract (SCE) on MAFLD and to elucidate the pharmacological mechanisms. <b>Methods:</b> A rat model of MAFLD was induced through a high-fat diet (HFD), and the model rats subsequently received SCE as a therapeutic intervention for six weeks. The analysis involved 16S rDNA sequencing, untargeted fecal metabolomics, and targeted bile acid metabolomics to investigate the effects of SCE on the gut microbiota and bile acid metabolism. <b>Results:</b> Hepatic steatosis and lipid accumulation were significantly alleviated by the SCE treatment. SCE treatment modulated the gut microbiota disorder, by enhancing the relative abundance of the beneficial gut microbiota, including <i>Clostridium</i>, <i>Oscillospira</i>, and <i>Romboutsia</i>. Untargeted fecal metabolomics revealed a significant enrichment of the metabolites in secondary bile acid biosynthesis. Targeted bile acid metabolomics revealed that SCE reversed the abnormal fecal bile acid metabolic profile, such as HDCA, LCA, and T-β-MCA. These changes activated FXR and PPARα receptors to improve the lipid metabolism by regulating bile acid synthesis. <b>Conclusions</b>: Our study provides evidence that SCE alleviates MAFLD through regulation of the gut microbiota, bile acid metabolism, and activation of the FXR/PPARα pathway, illustrating the mechanism of action of SCE in MAFLD from a novel perspective, and further highlights its therapeutic potential.