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<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) has been rising in prevalence. As an essential trace element, copper plays a crucial role in iron metabolism, lipid peroxidation, and fatty acid synthesis. Copper deficiency exacerbates MASLD progression by disrupting these metabolic processes. The processed black ginseng (BG) has abundant rare ginsenosides, such as Rg3 and Rk1, which have shown potential in alleviating hepatic steatosis and inflammation. In this study, the MASLD model was established in middle-aged mice by feeding a copper-deficient diet (&lt; 0.1&#xa0;mg/kg Cu) combined with a high-sugar solution. By integrating multi-omics approaches, including serum metabolomics, hepatic lipidomics, gut microbiome analysis, and molecular docking, we systematically investigated the therapeutic effects and underlying mechanisms of BG on MASLD. The results demonstrated that BG treatment significantly improved body weight regulation, reduced serum ALT and AST levels, corrected lipid abnormalities, and alleviated hepatic lipid accumulation. Multi-omics analyses revealed that BG exerted its effects primarily by modulating multiple metabolic pathways, including arachidonic acid, linoleic acid, retinol, and sphingolipid metabolism, thereby restoring liver-serum metabolic homeostasis. Moreover, BG improved gut microbiota composition by increasing the abundance of beneficial bacteria such as <i>Akkermansia</i> and <i>Faecalibaculum</i> while reducing the levels of pathogenic Proteobacteria. Molecular docking confirmed that BG-derived ginsenosides exhibited high binding affinity to key targets in arachidonic acid metabolism, including COX-2, 5-LOX, and PLA2. In conclusion, BG exerted hepatoprotective effects against MASLD by targeting multiple pathways and restoring gut-liver axis homeostasis. These findings provide theoretical and experimental support for the application of BG in MASLD intervention.</p> Graphical Abstract <p></p>

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Multi-Omics Investigation Reveals the Therapeutic Effect of Black Ginseng on Copper Deficiency and High-Sugar Induced Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Murine Models

  • 期刊论文

  • 发表日期：

    2026年1月28日

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  • Wei Wei,
  • Yuhua He,
  • Xiaoxiao Zhang,
  • Yang Wang,
  • Liming Liu

摘要

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been rising in prevalence. As an essential trace element, copper plays a crucial role in iron metabolism, lipid peroxidation, and fatty acid synthesis. Copper deficiency exacerbates MASLD progression by disrupting these metabolic processes. The processed black ginseng (BG) has abundant rare ginsenosides, such as Rg3 and Rk1, which have shown potential in alleviating hepatic steatosis and inflammation. In this study, the MASLD model was established in middle-aged mice by feeding a copper-deficient diet (< 0.1 mg/kg Cu) combined with a high-sugar solution. By integrating multi-omics approaches, including serum metabolomics, hepatic lipidomics, gut microbiome analysis, and molecular docking, we systematically investigated the therapeutic effects and underlying mechanisms of BG on MASLD. The results demonstrated that BG treatment significantly improved body weight regulation, reduced serum ALT and AST levels, corrected lipid abnormalities, and alleviated hepatic lipid accumulation. Multi-omics analyses revealed that BG exerted its effects primarily by modulating multiple metabolic pathways, including arachidonic acid, linoleic acid, retinol, and sphingolipid metabolism, thereby restoring liver-serum metabolic homeostasis. Moreover, BG improved gut microbiota composition by increasing the abundance of beneficial bacteria such as Akkermansia and Faecalibaculum while reducing the levels of pathogenic Proteobacteria. Molecular docking confirmed that BG-derived ginsenosides exhibited high binding affinity to key targets in arachidonic acid metabolism, including COX-2, 5-LOX, and PLA2. In conclusion, BG exerted hepatoprotective effects against MASLD by targeting multiple pathways and restoring gut-liver axis homeostasis. These findings provide theoretical and experimental support for the application of BG in MASLD intervention.

Graphical Abstract