Improvement of ellagic acid from Rosa roxburghii Tratt on MASLD via PPARγ signaling pathway

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a global health threat, necessitating natural therapeutics. Rosa roxburghii Tratt (RRT), a medicinal and edible resource, shows anti-MASLD potential but lacks defined bioactive components and mechanisms. Using UHPLC-HRMS analysis and network pharmacology, we identified ellagic acid (EA) as RRT’s primary bioactive component against MASLD. In high-fat diet (HFD)-fed mice and oleic acid (OA)-induced hepatocytes, EA alleviated hepatic steatosis, reduced serum and liver triglycerides (TG) and total cholesterol (TC), and lipid droplet-associated marker Plin2 expression. Mechanistically, EA inhibited PPARγ transcription and translation, and concurrently downregulated the mRNA expression of lipid metabolism–related genes associated with the PPARγ signaling pathway (Cebpa, Acc1, Fasn, Cd36, Hmgcr, Srebf2) in MASLD mice. Similar regulatory effects were also observed in two hepatic cell-based MASLD models (Acc1, Hmgcr and Srebf2). Pharmacological studies with PPARγ agonist (pioglitazone) and antagonist (GW9662) confirmed EA counteracts lipid dysregulation via PPARγ-dependency. This work establishes EA as a novel PPARγ-targeting phytochemical restoring hepatic lipid homeostasis, providing a molecular foundation for plant-derived MASLD interventions and highlighting RRT’s translational promise.