Protective Effect of Biobran/MGN-3 against Sporadic Alzheimer’s Disease Mouse Model: Possible Role of Oxidative Stress and Apoptotic Pathways

Mamdooh H Ghoneum,Nesrine S El Sayed,Kambiz Hassanzadeh

doi:10.1155/2021/8845064

Abstract

Alzheimer's disease (AD) is a debilitating and irreversible brain disease that affects an increasing number of aged individuals, mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent antioxidant, antiaging, and immunomodulatory effects. The aim of the present study was to investigate the protective effect of Biobran against sporadic Alzheimer's disease (SAD). SAD was induced in mice via intracerebroventricular injection of streptozotocin (STZ) (3 mg/kg). STZ-treated mice were administered with Biobran for 21 days. The effects of Biobran on memory and learning were measured via the Morris water maze, novel object recognition, and Y-maze tests. Biomarkers for apoptosis, oxidative stress, and amyloidogenesis were measured using ELISA and western blot analysis. Histopathological examination was performed to confirm neuronal damage and amyloid-beta deposition. Biobran reversed the spatial memory deficit in SAD-induced mice, and it increased the expression of glutathione, reduced malondialdehyde, decreased IL-6, decreased intercellular adhesion molecule-1 (ICAM-1), and significantly increased nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE). Moreover, Biobran exerted a protective effect against amyloid-beta-induced apoptosis via the suppression of both cleaved caspase-3 and the proapoptotic protein Bax and via the upregulation of the antiapoptotic protein Bcl-2. Furthermore, it reduced the expression of forkhead box class O proteins. It could be concluded from this study that Biobran may be a useful nutritional antioxidant agent for protection against SAD through its activation of the gene expression of Nrf2/ARE, which in turn modulates the apoptotic and amyloidogenic pathways.

Highlights

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive loss of memory and cognition
Mice treated with Biobran, on the other hand, had Mean escape latency (MEL) values that were similar to the sham control starting on day 2
The current study evaluated the protective effect of Biobran/MGN-3 against STZ-induced sporadic Alzheimer’s disease (SAD) in mice

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive loss of memory and cognition. The process by which amyloid-beta (Aβ) accumulation occurs in the central nervous system is uncertain, but the generation of ROS during Aβ selfaggregation is a potential mechanism by which Aβ may cause neuronal damage and death. This effect leads to synaptic membrane depolarization, excessive calcium influx, and mitochondrial impairment [4, 5]. One of the common regulators of the oxidative stress pathway in AD is the expression of the nuclear factor erythroid 2-related factor 2 (Nrf). The restoration of Nrf expression could alleviate cognitive impairment by protecting neurons against oxidative injury and decreasing Aβ accumulation [10]

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