Activation of CREB by St. John's wort may diminish deletorious effects of aging on spatial memory.

St. John's wort (Hypericum perforatum) is one of the leading psychotherapeutic phytomedicines. Beneficial effects of this herb in the treatment of mild to moderate depression are well known. In this study we tested a hypothesis that St. John's wort alleviates age-related memory impairments by increasing the levels of cyclic adenosine 3', 5'-monophosphate response element binding protein (CREB) and phosphorylated CREB (pCREB) in hippocampus. Middleaged rats (18 month-old) displayed a decline in the acquisition of spatial working memory (p < 0.001) in the Morris water maze (MWM). Chronic administration of Hypericum perforatum (HP) (350 mg/kg for 21 days), potently and significantly improved the processing of spatial information in the aged rats (p < 0.001). Also the herb increased the levels of pCREB in the aged rat's hippocampus (p < 0.01) as measured by western immunoblotting. Aging caused significant locomotor impairments as tested in the open field (p < 0.001) but not in the MWM test. However, these were unaffected by treatment with HP. Thus, this study indicates that St. John's wort effectively prevents aging-induced deterioration of spatial memory in 18 month-old rats, possibly by the activation of CREB regulated genes associated with memory formation. It appears that mechanism is probably inactive in young rats.