Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose

Ursolic acid (UA), a pentracyclic triterpene, is reported to have an antioxidant activity. Here we assessed the protective effect of UA against the D-galactose (D-gal)-induced neurotoxicity. We found that UA markedly reversed the D-gal induced learning and memory impairment by behavioral tests. The following antioxidant defense enzymes were measured: superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). The content of the lipid peroxidation product malondialdehyde (MDA) was also analyzed. Our results indicated that the neuroprotective effect of UA against D-gal induced neurotoxicity might be caused, at least in part, by the increase in the activity of antioxidant enzymes with a reduction in lipid peroxidation. And UA also inhibited the activation of caspase-3 induced by D-gal. Furthermore, we found that UA significantly increased the level of growth-associated protein GAP43 in the brain Of D-gal-treated mice. These results suggest that the pharmacological action of UA may offer a novel therapeutic strategy for the treatment of age-related conditions. (c) 2007 Elsevier Inc. All rights reserved.