Abstract
BackgroudUse of multifunctional drugs with neurotrophic supporting and oxidative stress suppressing activity may be considered a therapeutic strategy to protect or repair cellular damage caused during the progression of Alzheimer’s disease (AD). In this study, we investigated the therapeutic effects of aqueous extract of A. cochinchinesis root (AEAC), particularly its role as a nerve growth factor (NGF) stimulator and anti-oxidant in Tg2576 mice showing AD phenotypes of human.MethodsTg2576 mice were received 100 mg/kg/day AEAC via oral administration, while mice in the Vehicle treated group received dH2O for 4 weeks. Non-Tg littermates were used as a control group. Following AEAC treatment for 4 weeks, NGF function, anti-oxidantive status, Aβ-42 peptide level, γ-secretase expression and neuronal cell functions were analyzed in the brain of Tg2576 mice.ResultsAEAC containing flavonoids, phenols, saponins and protodioscin induced enhancement of NGF secretion and decreased intracellular ROS in the neuronal and microglial cell line. These effects as well as enhanced SOD levels were also detected in AEAC treated Tg2576 mice. The expression of p-Akt among downstream effectors of the high affinity NGF receptor was dramatically recovered in AEAC treated Tg2576 mice, while the expression of p75NTR was slightly recovered in the same group. Significant recovery on the level of Aβ-42 peptides and the expression of γ-secretase members including PS-2, APH-1 and NCT were detected in AEAC treated Tg2576 mice. Furthermore, AEAC treated Tg2576 mice showed decreased numbers of dead cells and suppressed acetyl choline esterase (AChE) activity.ConclusionsThese results suggest that AEAC contribute to improving the deposition of Aβ-42 peptides and neuronal cell injuries during the pathological progression stage of AD in the brain of Tg2576 mice through increased NGF secretion and suppressed oxidative stress.
Highlights
Alzheimer’s disease (AD) is a well known neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles in the hippocampus and the brain cortex that is accompanied by severe learning and memory impairment [1]
Protodioscin was detected as a sharp specific peak in the High performance liquid chromatography (HPLC) curve of AEAC at 14.1 min (Fig. 1a)
The IC50 value of AEAC was determined to be 590.1 μg/ml (Fig. 1b). These results demonstrate that AEAC contained various bioactive components with anti-oxidant activity, and that these were likely related to its neuroprotective effects
Summary
AD is a well known neurodegenerative disorder characterized by the presence of senile plaques and neurofibrillary tangles in the hippocampus and the brain cortex that is accompanied by severe learning and memory impairment [1]. Senile plaques are mainly composed of Aβ peptides produced from the β-amyloid precursor protein (APP), while neurofibrillary tangles contain hyperphosphorylated and nitrated tau protein [2,3,4]. These two key components stimulate progression of the AD pathological process and accumulation of these abnormal proteins in specific regions of the brain [4]. Various attempts have reported several pathological mechanisms as the main cellular targets to prevent or retard the progression of AD to disease states [2]. Many recent studies have focused on multi-target therapies at early stages of the disease as the most effective strategy because of the complex conditions of the Alzheimer neurodegenerative process [2, 14]
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