Exploring the Mechanisms of the Yueju Pill for ALD by Integrating UPLC-QE Orbitrap-MS/MS, Network Pharmacology, and...

This study integrated UPLC-QE Orbitrap-MS/MS, network pharmacology, and experimental validation to investigate the chemical profile and therapeutic mechanisms of the Yueju pill (YJP) in the treatment of alcoholic liver disease (ALD). Chemical analysis identified 91 compounds in the YJP. After SwissADME screening, 45 active ingredients were predicted as potential bioactive compounds. By overlapping the targets of these compounds with ALD-related targets, a "component-target-disease" network was constructed, revealing 183 common targets. Enrichment analysis indicated that YJP exerts its therapeutic effects through multiple pathways, including the HIF-1 signaling pathway. In animal experiments, an ALD mouse model was established using the Lieber-DeCarli ethanol liquid diet. YJP intervention significantly reduced serum TG, AST, and ALT levels, alleviated hepatic lipid deposition and collagen deposition, improved liver mitochondrial homeostasis, and decreased hepatic HIF-1α expression. Moreover, the YJP improved intestinal barrier integrity and upregulated intestinal HIF-1α and occludin expression, reflecting a therapeutic mechanism involving coordinated regulation of the gut-liver axis.