Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is a neurodegenerative brain disorder and the most common cause of dementia. New treatments for AD are required due to its increasing prevalence in aging populations. The present study evaluated the effects of the active components of Epimedium, Astragalus and Radix Puerariae on learning and memory impairment, β-amyloid (Aβ) reduction and brain iron load in an APPswe/PS1ΔE9 transgenic mouse model of AD. Increasing evidence indicates that a disturbance of normal iron homeostasis may contribute to the pathology of AD. However, the underlying mechanisms resulting in abnormal iron load in the AD brain remain unclear. It has been hypothesized that the brain iron load is influenced by the deregulation of certain proteins associated with brain iron metabolism, including divalent metal transporter 1 (DMT1) and ferroportin 1 (FPN1). The present study investigated the effects of the active components of Epimedium, Astragalus and Radix Puerariae on the expression levels of DMT1 and FPN1. The treatment with the active components reduced cognitive deficits, inhibited Aβ plaque accumulation, reversed Aβ burden and reduced the brain iron load in AD model mice. A significant increase was observed in the levels of DMT1-iron-responsive element (IRE) and DMT1-nonIRE in the hippocampus of the AD mouse brain, which was reduced by treatment with the active components. In addition, the levels of FPN1 were significantly reduced in the hippocampus of the AD mouse brain compared with those of control mice, and these levels were increased following treatment with the active components. Thus, the present study indicated that the active components of Epimedium, Astragalus and Radix Puerariae may exert a neuroprotective effect against AD by reducing iron overload in the AD brain and may provide a novel approach for the development of drugs for the treatment of AD.

Association of traditional Chinese medicine therapy and the risk of dementia in patients with hypertension: a nationwide population-based cohort study

“…Ge-Gen was found to show potential medicinal benefits in diabetes and cardiovascular and cerebrovascular diseases [34], and it could alleviate neurological deficits and improve learning and memory after ischemia/reperfusion-induced cerebral microcirculatory disturbances [35]. Recent studies have also demonstrated that Ge-Gen could inhibit Aβ plaque accumulation [36], suppress tau protein expression [37], and antagonize neuronal apoptosis induced by oxidative stress [38]. …”

The neuritogenic and synaptogenic effects of the ethanolic extract of radix Puerariae in cultured rat hippocampal neurons

“…In Korea, this medicinal herb is used as ethnomedicine for treating various diseases, including neuronal disorders. The reported neuroprotective effects of puerarin (Dong et al, 2015;Li et al, 2013;Zhu et al, 2014) have provided the support for its traditional use as a treatment for neuronal disorders, and reasonably prompted us to investigate the neurotrophic abilities of this ethnomedicine to the development of CNS neurons. It is worth mentioning that the development of a neuron involves a stereotypic progression of events, that is, the initiation of process outgrowth, axonal differentiation, dendritic arborization and the formation of synaptic connections.…”

“…Puerarin attenuates neuronal degeneration by protecting against 6-OHDA-mediated oxidative stress injury in substantia nigra . Active component of RP, i.e., puerarin, also exerts protection against Aβ-induced microglial apoptosis and in transgenic mouse model of AD (Dong et al, 2015;Wang et al, 2014). However, the effects of RP or its active compound, puerarin on the development of neural networks are unknown, and reasonably draw our attention as an interesting subject of investigation.…”

Development of a liquid chromatography–tandem mass spectrometry method for simultaneous determination of five isoflavonoids and seven neurochemicals in rat brain dialysate and its application to a pharmacological study

“…Several studies have also proved neuroprotective effect of the total pueraria isoflavones (PIF). According to animal studies, PIF could exert neuroprotective effect against the Alzheimer's disease by reducing iron overload in rat brain , as well as against ischemic damage based on its anti‐inflammatory properties . As reported, PIF showed potential preventative effect for memory‐related nervous disorders through modulating the formation of glutamatergic synapses and enhancing N‐methyl‐D‐aspartic acid receptor‐mediated postsynaptic currents .…”