Neurobiological effects of Hyperforin and its potential in Alzheimer's disease therapy.

St. John's Wort (SJW) has been used medicinally for over 5,000 years. Relatively recently, one of its phloroglucinol derivatives, hyperforin, has emerged as a compound of interest. Hyperforin first gained attention as the constituent of SJW responsible for its antidepressant effects. Since then, several of its neurobiological effects have been described, including neurotransmitter re-uptake inhibition, the ability to increase intracellular sodium and calcium levels, canonical transient receptor potential 6 (TRPC6) activation, N-methyl-D-aspartic acid (NMDA) receptor antagonism as well as antioxidant and anti-inflammatory properties. Until recently, its pharmacological actions outside of depression had not been investigated. However, hyperforin has been shown to have cognitive enhancing and memory facilitating properties. Importantly, it has been shown to have neuroprotective effects against Alzheimer's disease (AD) neuropathology, including the ability to disassemble amyloid-beta (Abeta) aggregates in vitro, decrease astrogliosis and microglia activation, as well as improve spatial memory in vivo. This review will examine some of the early studies involving hyperforin and its effects in the central nervous system (CNS), with an emphasis on its potential use in AD therapy. With further investigation, hyperforin could emerge to be a likely therapeutical candidate in the treatment of this disease.

Hyperforin prevents beta-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-beta-deposits.

The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid beta-peptide (Abeta). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Abeta-induced spatial memory impairments and on Abeta 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 Abeta-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Abeta 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 Abeta 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.