A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Aβ25–35

Peroxynitrite (ONOO−)-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Aβ) 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 Aβ25–35. Mice daily received i.p. several doses of RA after the injection of Aβ25–35. RA prevented the memory impairments induced by Aβ25–35 in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25 mg/kg), prevented Aβ25–35-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 Aβ25–35 blocked the protective effects of RA (0.25 mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Aβ25–35 is due to its scavenging of ONOO−, and that daily consumption of RA may protect against memory impairments observed in AD.