Protection of PC12 and differentiated PC12 cells from β-amyloid peptide-induced cell death by some natural compounds in food
Date Issued
2010
Date
2010
Author(s)
Hou, I-Huei
Abstract
Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder in aged people. AD impairs memory and cognitive skills. The hallmark is accumulation of β-amyloid peptide in the brain, leading to elevated oxidative stress, dysfunction of mitochondrial, synapse loss and leading to destroy brain function. PC12 is a neuronal-like cell line expressed several neurobiological characteristics. PC12 cells have been extensively used as an in vitro model of AD and neuron-related research. Our research is entitled ”Inhibition of aggregated Aβ-induced naïve PC12 (nPC12) and differentiated PC12 (dPC12) cells death” as an in vitro model, by using the standardized extract from the leaves of the Ginkgo biloba extract (EGb 761) as the positive control. To investigate the possible neuroprotective effects of arachidin-1 from peanut second metabolite, ferulic acid and z-ligustilide in Angelica sinensis, naturally occurred of gallic acid, proanthocyanidin A2 from Dimocarpus longan Lour. flowers extract, sesamol from sesame oil and tetrahydrocurcumin (THC) from curcumin metabolite. From our results, 20 - 40 μM (11.5 - 23.1 ppm) PA2 and 0.5 -2 μM (0.16 - 0.62 ppm) arachidin-1 in nPC12 cells could increase cell proliferation, and the efficiency was close to 100 - 200 ppm EGb 761. And 40 μM (23.1 ppm) PA2 and 2 μM (0.62 ppm) arachidin-1showed significant potential protective effect on aggAβ1-40 induced cell death (P<0.01), and the efficiency was close to 50 ppm EGb 761. PC12 was differentiated to dPC12 under the stimulation of nerve growth factor (NGF) and growed neurite-like properties. 40 μM (23.1 ppm) PA2, 1 μM (0.31 ppm) arachidin-1, 20 μM (3.4 ppm) gallic acid and 10 ppm 50 % z-ligustilide in dPC12 cells showed significant potential protective effect on aggAβ1-40 induced cell death (P<0.05), and the efficiency of 40 μM (23.1 ppm) PA2 is better than 50 ppm EGb 761. Arachidin-1, PA2 and gallic acid had strong antioxidant effect in CAA and DPPH assays. Arachidin-1, PA2, gallic acid and z-ligustilide could disaggregate aggAβ1-40 oligomers. The results suggested that arachidin-1, PA2 and gallic acid decreased aggAβ1-40 induced cytotoxicity possibly by decreasing the oxidative stress and disaggregated activity. Z-ligustilide decreased aggAβ1-40 induced cytotoxicity possibly by disaggregated activity and other mechanisms. By these mechanisms, therefore, we suggested that arachidin-1, PA2, gallic acid and z-ligustilide had potential neuroprotective activity against aggAβ1-40 induced cytotoxicity
Subjects
β-amyloid peptide
oxidative stress
Type
thesis
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