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

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.

α7 nicotinic ACh receptors are necessary for memory recovery and neuroprotection promoted by attention training in amyloid‐β‐infused mice

“…On the other way, animals that were infused only with Aβ and submitted to the weekly attention training presented evident and significant improvements in memory, which were not observed with animals infused with Aβ + MLA or only MLA. As we have shown before, the chronic infusion of Aβ during 4-5 weeks promote memory loss in mice and rats with deposition of Aβ senile plaques Morzelle et al, 2016;Viel et al, 2012).…”

Antiinflammatory and anti‐cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies

“…In another study, Morzelle et al evaluated the antiinflammatory effects of PPE following chronic brain infusion of Aβ in mice. They found that PPE (800 mg/kg/day) notably attenuated the levels of amyloid plaque density, acetylcholinesterase activity, lipid peroxidation, and TNF‐α (Morzelle et al, ). Hydroethanolic (50% v/v) extract of pomegranate peel contains a large amount of PU, PL, and EA, which can provide synergistic effects using together.…”

Targeted metabolite profiling to gain chemometric insight into Indian pomegranate cultivars and elite germplasm

“…Sinapic acid is known to exhibit anticancerous, antiglycemic, and neuro‐protective activities that have the potential to attenuate various chemically induced toxicities . Ellagic acid is known for neuro‐protective effects and has been shown to be beneficial in the treatment of Parkinson's disease . Antioxidant activity (AOX) in pomegranate juice ranged from 7.53 to 14.27 mmol L −1 (Table ).…”

“…Among these, punicalagin, anthocyanins, and ellagic acid are some of the most important compounds responsible for the anti‐inflammatory activity and antimicrobial activity in pomegranate juice. Epidemiological studies have demonstrated beneficial effects of pomegranate‐juice consumption in reducing the risk of cardiovascular disease, diabetes, and neuro‐degeneration …”