Abstract

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid β-peptide (Aβ). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Aβ-induced spatial memory impairments and on Aβ neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Aβ-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Aβ oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Aβ aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease. © 2006 Nature Publishing Group. All rights reserved.