Neuroprotective Effects of the Methanol Extract of Angelica sinensis and Its Bioactive Components Against Aβ-induced Toxicity in Rat Cortical Neurons
Date Issued
2012
Date
2012
Author(s)
Chen, Ying-Ting
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline in memory, orientation, judgment, and reasoning; it is also the most common cause of dementia among the elderly. Neuropathologically, it is characterized by the accumulation of extracellular plaques and intracellular neurofibrillary tangles (NFTs). Plaques are mainly comprised of a small peptide called amyloid-β (Aβ),and neurofibrillary tangles are consisting of aggregates of hyperphosphorylated tau protein. Recent researches suggested that soluble oligomers may be the aggregating species responsible for Aβ neurotoxicity. Because there is no known cure for AD, developing a prevention of AD is important. Therefore, the objective of this study is to find potential phytochemicals that can protect the neuron against Aβ-induced toxicity. Methanol extract of Anglica sinensis (As-M) was proven to have protective potential in dPC12 cell model against Aβ-induced toxicity in our laboratory. Z-ligustilide (Z-LIG) is thought to be the most biologically active component in Anglica sinensis. Ferulic acid is a phenolic compound contained in Angelica sinensis, has been demonstrated that long-term administration of ferulic acid (FA) induces resistance to Aβ1-42 toxicity in the brain. We plan to use As-M and mixtures of the two compounds to evaluate their potential neuroprotective effect against Aβ-induced toxicity in primary rat cortical neurons by assessing the cell viability with MTT colorimetric assay and further investigate their mechanism of action. FA (75 μM) and Z-LIG (25 μM) showed significant protective effect to primary rat cortical neurons against Aβ1-42 toxicity, their inhibitory ratios were 28.6% and 24.0%, respectively. But As-M did not show significant protective effect against Aβ1-42 toxicity. Therefore, we mixed FA and Z-LIG to test their protective effect to primary rat cortical neurons. Our results suggested that Z-LIG and FA did not show a synergistic effect in this regard. In aggrregated human Aβ ELISA assay, EGb761, Z-LIG and FA were found to reduce the production of Aβ1-42 oligomers, indicating that these compounds may protect neuron through accelerating Aβ assembly.
Subjects
Alzheimer’s disease (AD)
amyloid-β (Aβ)
primary rat cortical neuron
Angelica sinensis
Z-ligustilide
ferulic acid
SDGs
Type
thesis
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