Dendrobine’s mechanism: alleviating cholesterol metabolism disorders via FXR/LXR modulation in NAFLD mouse livers
- 1Key Lab of the Basic Pharmacology of the Ministry of Education, Zunyi Medical University, Guizhou Engineering Research Center of Industrial Key-technology for Dendrobium Nobile, Zunyi Medical University , , ,
- 2Guizhou Engineering Research Center of Industrial Key-technology for Dendrobium Nobile, Guizhou Engineering Research Center for Orchid Medicinal Plant Breeding and Efficient Application, Zunyi Medical University , , ,
Abstract
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 Dendrobium nobile , has emerged as a potential therapeutic candidate for lipid metabolic disorders.
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 via histology and biochemical assays; bile acid profiles were quantified by LC-MS/MS. Gene and protein expression were analyzed using RT-qPCR and Western blotting. In vitro studies using cholesterol-laden HepG2 cells further explored DNE’s mechanisms, validated by specific pharmacological agonists and inhibitors of the Farnesoid X receptor (FXR) and liver X receptor (LXR) pathways.
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., Cyp7a1 ) and efflux, while downregulating transporters responsible for BA and cholesterol reuptake (e.g., Ntcp , Npc1l1 ). In vitro validation using specific pharmacological agonists and antagonists further confirmed that DNE upregulates CYP7A1 and promotes BA synthesis via a dual FXR/LXRα-dependent regulatory network.
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.
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BibTeX
@article{chen2026dendrobines,
title = {{Dendrobine’s mechanism: alleviating cholesterol metabolism disorders via FXR/LXR modulation in NAFLD mouse livers}},
author = {Zhi Chen and Yi Luo and Yanzhe Xu and Jiaying Li and Zaishuang He and Yichen Gao and Jianyuan Liu and Di Wu and Lin Qin and Daopeng Tan and Yuqi He and Yanliu Lu},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1875005},
url = {https://europepmc.org/article/PMC/PMC13672324},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dendrobine’s mechanism: alleviating cholesterol metabolism disorders via FXR/LXR modulation in NAFLD mouse livers
AU - Zhi Chen
AU - Yi Luo
AU - Yanzhe Xu
AU - Jiaying Li
AU - Zaishuang He
AU - Yichen Gao
AU - Jianyuan Liu
AU - Di Wu
AU - Lin Qin
AU - Daopeng Tan
AU - Yuqi He
AU - Yanliu Lu
PY - 2026
DA - 2026/10/02
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1875005
UR - https://europepmc.org/article/PMC/PMC13672324
AB - 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 Dendrobium nobile , has emerged as a potential therapeutic candidate for lipid metabolic disorders. 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 via histology and biochemical assays; bile acid profiles were quantified by LC-MS/MS. Gene and protein expression were analyzed using RT-qPCR and Western blotting. In vitro studies using cholesterol-laden HepG2 cells further explored DNE’s mechanisms, validated by specific pharmacological agonists and inhibitors of the Farnesoid X receptor (FXR) and liver X receptor (LXR) pathways. 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., Cyp7a1 ) and efflux, while downregulating transporters responsible for BA and cholesterol reuptake (e.g., Ntcp , Npc1l1 ). In vitro validation using specific pharmacological agonists and antagonists further confirmed that DNE upregulates CYP7A1 and promotes BA synthesis via a dual FXR/LXRα-dependent regulatory network. 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.
SN - 1663-9812
ER -