Quercetin Ameliorates Glucose Metabolism Dysregulation in CUMS Model Rats <i>via</i> the Bile Acid–FXR/TGR5 Axis

Quercetin, a plant-derived flavonoid, has demonstrated therapeutic potential across metabolic and neuropsychiatric disorders. This study aimed to clarify the mechanisms by which quercetin mitigates glucose metabolic dysfunction in rats subjected to chronic unpredictable mild stress (CUMS), with a particular focus on its regulation of the bile acid-farnesoid x receptor (FXR)/takeda g protein-coupled receptor 5 (TGR5) signaling pathway. Behavioral assessments and histopathological, biochemical, immunofluorescence, Western blotting, and targeted metabolomics analyses showed that quercetin significantly alleviated depressive-like behaviors and ameliorated glucose metabolic dysregulation. Quercetin treatment modified bile acid composition in colonic contents, activated the FXR/TGR5 pathway, and enhanced glucagon-like peptide-1 (GLP-1) secretion, collectively contributing to improved glycemic and lipid homeostasis. These results indicate that quercetin attenuates CUMS-induced glucose metabolic disturbances via the bile acid-FXR/TGR5-GLP-1 axis, suggesting its potential as a dual-target therapeutic agent for stress-related metabolic and neurobehavioral disorders.