Unraveling the ameliorative effects of Ling-Gui-Zhu-Gan decoction on MASLD: an integrative gut microbiota and lipidomic study.

BACKGROUND: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been continuously increasing. However, the pathogenesis of MASLD is quite complex and involves multiple factors, leading to a lack of targeted therapeutic drugs for MASLD. Ling-Gui-Zhu-Gan Decoction (LGZGD) has demonstrated significant hepatoprotective and lipid-lowering effects, yet its mechanism of action against MASLD remains incompletely understood. METHODS: In this study, we established a high-fat diet-induced MASLD rat model to investigate the pharmacological effects of LGZGD on MASLD from the perspectives of gut microbiota and lipidomics. RESULTS: Using UPLC-Q-TOF-MS analysis, we putatively identified 83 chemical components in LGZGD, primarily flavones and terpenoids, which may represent the key active constituents responsible for its ameliorative effects. In MASLD model rats, LGZGD treatment reduced the levels of TC, TG, AST, ALT, and LDL-C in both serum and liver tissue, while increasing HDL-C levels. Analysis of the gut microbiota revealed that LGZGD treatment increased the abundance of g__Collinsella and g__Prevotellaceae_UCG-003, and decreased the abundance of g__Faecalibaculum. Furthermore, LGZGD was found to regulate 831 lipids, primarily involved in metabolic pathways such as glycerophospholipid, glycerolipid, and sphingolipid metabolism. CONCLUSIONS: This study demonstrates that LGZGD prevents MASLD, and its mechanism of action involves the regulation of gut microbiota and the modulation of lipid metabolism.