Active compounds of herbs ameliorate impaired cognition in APP/PS1 mouse model of Alzheimer's disease.

Wenjun Yu,Xiqing Chai,Hongjun Xu,Tiemei Shao,Hongxu Chen,Yongjie Zhou,Shengjun An,Junda Ning

doi:10.18632/aging.102522

Abstract

Alzheimer’s disease (AD), the most common cause of dementia, is a neurodegenerative disorder characterized by amyloid plaque accumulations, intracellular tangles and neuronal loss in certain brain regions. It has been shown that a disturbance of normal iron metabolism contributes to the pathophysiology of AD. However, the mechanism underlying abnormal iron load in the brain of AD patients is unclear. The frontal cortex, an important brain structure for executive function, is one of the regions affected by AD. We investigated the beneficial effects of active compounds of Epimedium, Astragaoside and Puerarin on iron metabolism in the frontal cortex of six-month-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse, a model of AD. Treatment with the active compounds reduced cognitive and memory deficits and damaged cell ultrastructure in APP/PS1 mice. These beneficial effects were associated with changes in expression levels of iron metabolism proteins in the frontal cortex, including divalent metal transporter with iron response element (DMT1-with IRE), divalent metal transporter without iron response element (DMT1-without IRE), transferrin (TF) and transferring receptor 1 (TfR1); three release proteins including the exporter ferroportin 1 (Fpn1), ceruloplasmin (CP) and hephaestin (HEPH), one increased storage iron protein ferritin and one iron regulating hormone hepcidin. These findings suggest that the active compounds improve cognition and memory in brain neurodegenerative disorders and these beneficial effects are associated with reduced impairment of iron metabolism. This study may provide a new strategy for developing novel drugs to treat AD.

Highlights

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder that leads to cognitive impairment and dementia
We investigated the beneficial effects of active compounds of Epimedium, Astragaoside and Puerarin on iron metabolism in the frontal cortex of sixmonth-old APPswe/PS1ΔE9 (APP/PS1) double transgenic mouse, a model of AD
All these results indicate that the ability of the mice to apply spatial cues to the localization of the platform was impaired in the AD group (P

Summary

Introduction

AD is a devastating neurodegenerative disorder that leads to cognitive impairment and dementia. The etiology of AD involves a variety of pathophysiological factors, among which dysfunctional homeostasis of transition metals, altered iron metabolism, is one of the causes that play an important role in the pathogenesis of AD [1, 2]. Iron is a redox active metal that exists in the ferrous or ferric state, which is involved in many metabolic functions [3]. Age-related increase in iron levels in the brain has been proposed as a biomarker of cognitive defect and progression of neuroanatomical aging in healthy adults [6]. Previous studies have demonstrated that redox-active iron is closely associated with AD plaques and neurofibrillary tangles [4, 7]. The disturbances of iron metabolism might occur at several biological pathways, including iron uptake, release, storage and regulation of functional iron proteins at both the cellular and systemic levels [9]

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