Dendrobine's mechanism: alleviating cholesterol metabolism disorders via FXR/LXR modulation in NAFLD mouse livers.

Background: Cholesterol homeostasis is tightly regulated through hepatic synthesis, intestinal absorption, and biliary excretion, with bile acids serving as critical regulators of cholesterol catabolism. Dysregulated cholesterol metabolism and bile acid imbalance are hallmarks of non-alcoholic fatty liver disease (NAFLD), contributing to hepatic lipid accumulation and disease progression. Dendrobine (DNE), a bioactive alkaloid from Methods: C57BL/6J mice were fed a high-fat diet to establish an NAFLD model, followed by DNE administration. Hepatic steatosis and cholesterol deposition were evaluated Results: DNE significantly ameliorated hepatic steatosis and reduced cholesterol accumulation in HFD-induced NAFLD mice. LC-MS/MS analysis revealed that DNE substantially expanded the bile acid (BA) pool in the liver, bile, and ileum. Mechanistically, DNE comprehensively modulated cholesterol absorption, biotransformation, and transport by modulating the FXR and LXR signaling pathways. It robustly upregulated key genes involved in BA synthesis (e.g., Conclusion: Our findings suggest that DNE modulates cholesterol homeostasis and alleviates NAFLD in conjunction with BA synthesis, transport, and absorption, in a manner associated with the FXR/LXRα regulatory network, presenting a promising therapeutic strategy.