Mechanistic Study of Yang-gan-jie-yu Granules in Treating Postmenopausal Metabolic-Associated Fatty Liver Disease Based on Transcriptomics and Network Pharmacology

Objective: This study aimed to evaluate the therapeutic effects of Yang-gan-jie-yu Granules (YGJY) on a high-fat diet-induced postmenopausal metabolic-associated fatty liver disease (MAFLD) rat model, and to investigate the underlying mechanism of hepatic steatosis amelioration through integrated transcriptomic and network pharmacology approaches. Methods: Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) was employed to characterize chemical constituents of YGJY. A postmenopausal MAFLD rat model was established, followed by YGJY intervention. Hepatic transcriptome profiles were profiled using RNA sequencing, integrated with KEGG pathway enrichment analysis via network pharmacology. Finally, critical pathways were experimentally validated by western blotting. Results: Transcriptomic analysis revealed enrichment in fatty acid biosynthetic processes and estrogen signaling pathways, with Calml3 and Acacb identified as core targets. Network pharmacology predicted AMPK signaling as the central mechanism. Integrative analysis indicated that YGJY exerted therapeutic effects via the ERα/AMPK/ACC pathway, subsequently confirmed by western blot analysis. Conclusion: YGJY suppresses hepatic lipid accumulation by modulating the ERα/AMPK/ACC signaling pathway, thereby ameliorating postmenopausal MAFLD. These findings may offer novel strategies for clinical management of this condition.