Neuroprotective Effects of Pomegranate Peel Extract after Chronic Infusion with Amyloid-β Peptide in Mice.

Hudson Sousa Buck,Madepalli K. Lakshmana,Tania Araujo Viel,Maressa Caldeira Morzelle,Patricia Bachiega,Danilo Mourelle,Jocelem Mastrodi Salgado,Milena Telles

doi:10.1371/journal.pone.0166123

Abstract

Alzheimer’s disease is a chronic and degenerative condition that had no treatment until recently. The current therapeutic strategies reduce progression of the disease but are expensive and commonly cause side effects that are uncomfortable for treated patients. Functional foods to prevent and/or treat many conditions, including neurodegenerative diseases, represent a promising field of study currently gaining attention. To this end, here we demonstrate the effects of pomegranate (Punica granatum) peel extract (PPE) regarding spatial memory, biomarkers of neuroplasticity, oxidative stress and inflammation in a mouse model of neurodegeneration. Male C57Bl/6 mice were chronically infused for 35 days with amyloid-β peptide 1–42 (Aβ) or vehicle (control) using mini-osmotic pumps. Another group, also infused with Aβ, was treated with PPE (p.o.– βA+PPE, 800 mg/kg/day). Spatial memory was evaluated in the Barnes maze. Animals treated with PPE and in the control group exhibited a reduction in failure to find the escape box, a finding that was not observed in the Aβ group. The consumption of PPE reduced amyloid plaque density, increased the expression of neurotrophin BDNF and reduced the activity of acetylcholinesterase enzyme. A reduction in lipid peroxidation and in the concentration of the pro-inflammatory cytokine TNF-α was also observed in the PPE group. No hepatic lesions were observed in animals treated with PPE. In conclusion, administration of pomegranate peel extract has neuroprotective effects involving multiple mechanisms to prevent establishment and progression of the neurodegenerative process induced by infusion with amyloid-β peptide in mice.

Highlights

Alzheimer’s disease (AD) is a neurodegenerative condition related to the aging process with no cure until recently
Pomegranate peel extract has a high amount of phenolic compounds (21.25 ± 0.16 mg of gallic acid/g) and flavonoids (7.60 ± 0.12 mg quercetin/g), which are important natural antioxidants
At the end of the infusion period and treatment, body weights of animals infused with amyloid-β peptide 1–42 (Aβ), whether treated or not treated with pomegranate peel extract (PPE) (Aβ: 29.13 ± 0.35 g and Aβ + PPE: 28.05 ± 0.53 g), were similar to body weights of the control group (29.71 ± 0.54 g, P = 0.36)

Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative condition related to the aging process with no cure until recently. The current interest in the benefits to human health of antioxidant compounds of fruits has led to many research projects in the field of AD [1]. The pomegranate (Punica granatum) is a rich source of bioactive compounds with antioxidant capacity [2]. Studies have shown that this fruit has numerous benefits to human health, which has increased interest in studying its therapeutic properties [3]. In mouse models of AD, the consumption of a diet rich in pomegranate pulp or the direct consumption of the fruit’s juice increased behavioral performance and reduced amyloid plaque deposition in the hippocampus by 50%. The phenolic compounds of pomegranate pulp may be responsible for these therapeutic effects [4], and the ethanolic extract was effective in doses of 800mg/kg/day [5]

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