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

Abstract

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

Apolipoprotein E3 (ApoE3) but Not ApoE4 Protects against Synaptic Loss through Increased Expression of Protein Kinase Cϵ

“…Viability Assay-Viability of cells was measured by an MTT assay (39). For the MTT assay, 3.2 ϫ 10 4 primary hippocampal neurons from 18-day-old embryonic Sprague-Dawley rat brains were plated on each well of 24-well plates coated with poly-D-lysine.…”

Hyperforin promotes mitochondrial function and development of oligodendrocytes

“…Hyperforin prevents ROS release through inhibiting the activation of immune cells in rat brains (Cabrelle et al, 2008). Hyperforin has also prevented the β-amyloid induced neurotoxicity to hippocampal neurons in a rodent model by preventing the β-amyloidinduced ROS and inflammation (Dinamarca et al, 2006). A standard extract of SJW can increase the gene expression of antioxidant enzymes on rotenone-exposed rats (Sanchez- Reus et al, 2007).…”

Neurocognitive Improvement Through Plant Food Bioactives: A Particular Approach to Alzheimer’s Disease

“…Similarly, Mori et al (2013) observed that ferulic acid (30 mg/kg b.w.) reversed transgene-associated behavioral deficits and decreased brain parenchymal and cerebral vascular b-amyloid deposits and also hyperforin at 6 µM (Dinamarca et al 2006). Moon et al (2014) proved that the phenylpropanoid, 6-shogaol, at 10 mg/kg b.w.…”