Abstract

Metal chelating agents are antioxidant agents, which decrease the reductive potential and stabilize the oxidized metal ion form. In this study, we evaluated the naringin capacity in chelating iron and preventing amyloid-beta plaque formation in the hippocampus of iron-overloaded mice. Thirty-five NMRI male mice (8–10 weeks old) were provided. The mice were classified into five groups. Iron dextran was administered as i.p. injection (100 mg/kg/day) four times a week for four subsequent weeks. The treated groups received 30 and 60 mg/kg/day naringin for a month. After histological processing, the brain sections were stained with Perls’ stain kit for iron spots, and Congo red was used to stain the brain and hippocampus for amyloid-beta plaques. 30 mg/kg/day of naringin was shown to decrease nonheme iron in an efficient manner; iron content in this group decreased to 16.83 ± 0.57 μg/g wet weight, a quantity as low as that observed in the normal saline-receiving group. The nonheme iron content in the mice receiving 60 mg/kg/day of naringin was 20.73 ± 0.65 μg/g wet weight. In addition, Aβ plaque numbers in CA1, CA3, and DG areas of the hippocampus decreased significantly following treatment with 30 or 60 mg/kg/day naringin. Naringin has a strong iron chelation capacity and is able to reduce the formation of amyloid plaques. So it can be useful for neuroprotection and prevention of Alzheimer’s disease.

Highlights

  • Alzheimer’s disease (AD) is a common neurodegenerative disorder affecting more than 30 million people around the world that is characterized by amyloid-beta (Aβ) deposition in brain tissues (Chan et al, 2016; Thomas et al, 2020)

  • Our results show that the iron chelation activity of naringin was 83 ± 2.01%

  • EDTA was used as a standard [inhibition concentration 50 (IC50) 18.27 ± 0.09 μg ml-1]

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Summary

Introduction

Alzheimer’s disease (AD) is a common neurodegenerative disorder affecting more than 30 million people around the world that is characterized by amyloid-beta (Aβ) deposition in brain tissues (Chan et al, 2016; Thomas et al, 2020). Aβ chelates heavy metals such as iron, copper, and zinc, resulting in their deposition in the hippocampus, which in turn launches the Fenton reaction Used iron chelators, such as deferiprone, deferasirox, and deferoxamine (DFO), are of chemical nature and exhibit diverse side effects (Kontoghiorghes et al, 2010; Grady et al, 2013). Diverse biological activities have ever been discovered for these compounds, including antioxidant activity, anti-inflammatory activity, iron chelation activity, and neuroprotective effects (Mandel et al, 2007; Choi et al, 2012)

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