Hepatoprotective effects of propolis ethanol extract on D-galactose-induced aging mice: A metabolomics and transcriptomics analysis focusing on insulin resistance pathways

This study aimed to evaluate the hepatoprotective effects of Propolis ethanol extract (PEE) in D-galactose (D-gal)-induced senescence mice and explore its underlying mechanisms. Mice were administered PEE by gavage, and body weight, organ index, and serum biomarkers (SOD, MDA, AST, ALT) were measured. Liver histopathological changes were examined using HE staining. Additionally, transcriptomics and metabolomics analyses were employed to elucidate the molecular mechanisms. The results demonstrated that PEE ameliorated the reductions in body weight and liver index in aged mice. PEE significantly increased serum SOD levels and reduced MDA, AST, and ALT levels. Histological analysis revealed that PEE mitigated liver damage. Mechanistically, PEE appeared to exert hepatoprotective effects by modulating the insulin resistance pathway, particularly through the PI3K-AKT/PP1 signaling axis, thereby enhancing glycogen synthesis in the damaged liver. These findings provide a scientific foundation for the therapeutic potential of PEE in anti-aging and liver disease. Mechanisms by which PEE alleviates D-gal-induced liver injury in senescent mice. • PEE has ameliorative effects on liver injury in senescent mice. • PEE exerts hepatoprotective effects by modulating insulin resistance pathway. • PEE restores glycogen synthesis capacity in senescent liver. • The PI3K-AKT/PP1 signaling pathway is involved in the hepatoprotective effects of PEE.