Anti-Alzheimer’s disease potential of extracts of Agaricus blazei and several pure compounds in PC-12 cell model
Date Issued
2009
Date
2009
Author(s)
Chiu, Hung-Chih
Abstract
Alzheimer’s disease (AD) is the most common form of dementia caused by accumulation of amyloid-beta (Aβ) peptide in the brain, leading to elevated oxidative stress, inflammation, and neuronal loss in the brain. PC-12 cells, a neuronal-like cell line, were treated with Aβ to simulate the toxicity of Aβ towards neuron cells in AD. Several samples with high antioxidative activity including gallic acid, proanthocyanidin A2, arachidin-1, and sesamol, which is able to pass through the blood-brain-barrier (BBB), and samples with immunomodulating activities including tetrahydrocurcumin, Agaricus blazei, were used in Aβ treated PC-12 cells to evaluate the potential of these samples in the prevention of AD. Several methods for the preparation of toxic aggregates of Aβ1-40 fragment failed to exhibit significant toxicity towards PC-12 cells. The shorter active fragment Aβ25-35 was used instead, and H2O2 was also applied to mimic the elevated oxidative stress observed in neurons treated by Aβ. Result showed that differentiated PC-12 cells formed neurites and were more sensitive to toxicity of samples, but more resistance towards oxidative stress induced by H2O2. Both proanthocyanidin A2 and arachidin-1 exhibited protective effect in naïve PC-12 cells towards both Aβ25-35 and H2O2 damage. Ethanol and water extracts of A. blazei did not protect naïve PC-12 cells from Aβ25-35 toxicity, but was effective in protection of H2O2 damage. However, all the samples failed to protect differentiated PC-12 cells from H2O2 insult. Of the pure compound used, gallic acid, tetrahydrocurcumin, proanthocyanidin A2, arachidin-1 all exhibited stronger DPPH scavenging ability than trolox, followed by sesamol and α-tocopherol, with the extracts of A. blazei exhibiting poor scavenging abilities. The results suggest that proanthocyanidin A2, arachidin-1 exhibited protection against Aβ25-35 in naïve PC-12 cells, possibly by decreasing the elevated oxidative stress caused by Aβ25-35. Ethanol and water extracts of A. blazei were poor in DPPH scavenging ability yet protected naïve PC-12 cells from H2O2, implicating mechanism of actions other than direct antioxidative activity.
Subjects
Amyloid-beta
PC-12 cells
Type
thesis
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