Plantagoside Alleviate Hepatic Inflammation, Oxidative Stress and Histopathological Damage in D‐Galactose‐Induced Senescent Mice by Modulating Purine Metabolic Pathways

In this study, we aimed to investigate the hepatoprotective effects of plantagoside (PLA) against D-galactose (D-gal)-induced liver injury in aged mice. PLA treatment significantly alleviated the D-gal-induced body weight loss and the elevated liver index in mice, and effectively reduced oxidative stress, inflammatory response, and liver tissue damage in vivo. Transcriptomic analysis identified 513 differentially expressed genes (DEGs) regulated by PLA, and enrichment analysis revealed that these genes were primarily associated with the PI3K-Akt signaling pathway and purine metabolism. Metabolomic analysis revealed that PLA regulates purine metabolism by modulating key metabolites, such as hypoxanthine and cAMP. Integrated omics analysis suggested that PLA exerts protective effects by regulating purine metabolism, thereby enhancing antioxidant capacity and suppressing inflammation. In conclusion, PLA significantly alleviated D-gal-induced liver injury, reduced oxidative stress, and attenuated inflammation by regulating purine metabolism, thereby demonstrating its potential as an anti-aging and hepatoprotective drug and providing a new theoretical basis for the treatment of age-associated liver diseases.