Peroxynitrite (ONOO(-))-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Abeta) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO(-), on the memory impairment in a mouse model induced by acute i.c.v. injection of Abeta(25-35). Mice daily received i.p. several doses of RA after the injection of Abeta(25-35). RA prevented the memory impairments induced by Abeta(25-35) in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25mg/kg), prevented Abeta(25-35)-induced nitration of proteins, an indirect indicator of ONOO(-) damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO(-)-i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO(-) with Abeta(25-35) blocked the protective effects of RA (0.25mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Abeta(25-35) is due to its scavenging of ONOO(-), and that daily consumption of RA may protect against memory impairments observed in AD.
