Preventive mechanisms of Potentilla longifolia against MASLD based on chemical profiling, network pharmacology, and metabolomics

Potentilla longifolia D. F. K. Schltdl. (GYC), a common edible vegetable in Inner Mongolia and a botanical resource historically recognized in northeastern China for its health-promoting benefits, was investigated for its prophylactic effects against metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, 25 major bioactive constituents were characterized via UHPLC-QE-MS, providing a chemical blueprint for subsequent integrated network pharmacology and untargeted metabolomics analysis. Metabolic profiling of serum and liver tissue identified 18 and 15 differential metabolites, respectively, highlighting the AMPK and NF-κB axes as primary regulatory hubs. In vivo and in vitro experimental validations demonstrated that GYC intervention effectively prevented high-fat diet (HFD)-induced obesity, hepatic steatosis, and early hepatic injury. Mechanistically, GYC maintained lipid homeostasis and early hepatic inflammatory responses by activating the AMPK signaling axis and suppressing the NF-κB/MAPK pathways. These findings provide a robust scientific rationale for utilizing GYC as a functional food resource or a promising prophylactic agent for the prevention of MASLD.