Aging is an inevitable process featured by intelligence decline, behavioral disorders and cognitive disability.Increasing evidence indicates that oxidative stress plays a key role in the senescent development.Our previous study demonstrated that Saponins from Panax japonicus has a significant anti-oxidative effect in vitro.So the aim of the present study was to investigate the brain protective role of Saponins from Panax japonicus and its underlying mechanism.Mice were subcutaneously injected with D-galactose (D-gal, 150mg/kg per day)for 8 weeks and administered Saponins from Panax japonicus simultaneously.After 8 weeks of treatment, the animal behavior was observed in the open field test and water maze test, and the morphology of hippocampus was detected.The activities and mRNA expressions of antioxidant enzymes as well as the level of malondialdehyde (MDA) were evaluated.The extent of apoptosis was examined by TUNEL assay.The results indicate that Saponins from Panax japonicus markedly ameliorates the D-gal induced learning and memory impairment in both open field test and Morris water maze.Biochemical examination and RT-PCR method revealed that Saponins from Panax japonicus significantly increases the decreased activities and mRNA expressions of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) and decreases the raised malondialdehyde (MDA) content in the serum and brain of aging mice induced by D-gal.Furthermore, Saponins from Panax japonicus significantly attenuates the D-gal-induced neuronal degeneration and apoptosis in the hippocampus.These results indicate that Saponins from Panax japonicus has a potential protect role on brain aging mice induced by D-gal and its mechanism, at least in part, via modification of the redox system in the organism.