title: Pomegranate extract modulates processing of amyloid-β precursor protein in an aged Alzheimer's disease animal model.
abstract: Accumulating research supports the neuroprotective effects of pomegranate (Punica granatum) juice and extracts against Alzheimer's disease (AD) but there is limited data available in animal models. Here we investigated the effects of a standardized pomegranate extract (PE) on AD pathology in an aged transgenic AD animal model (R1.40).The mice (age 24-30 months) received either PE (at 100 and 200 mg/kg) or a control solution daily for three weeks, and were evaluated in the Morris water maze and the Y-maze for improvements in spatial long-term and working memory functions. Cortical amyloid-β precursor protein (APP) and amyloid-β (Aβ) levels, along with other relevant biomarkers for AD, were measured in brain tissues. PE did not improve cognitive performance of the mice, but altered levels and ratio of the Aβ42 and Aβ40 peptides which would favor a diminution in AD pathogenesis. Further analysis revealed that this reversal could be the product of the modification of γ-secretase enzyme activity, the enzyme involved in the generation of these Aβ isoforms. Our findings support a specific anti-amyloidogenic mechanism of a pomegranate extract in this aged AD animal model.
authors.forename: Aseef H
authors.initials: AH
authors.lastname: Ahmed
authors.forename: Gehad M
authors.initials: GM
authors.lastname: Subaiea
authors.forename: Aseel
authors.initials: A
authors.lastname: Eid
authors.forename: Liya
authors.initials: L
authors.lastname: Li
authors.forename: Navindra P
authors.initials: NP
authors.lastname: Seeram
authors.affiliation: 7 Greenhouse Road, Kingston, RI, United States. nzawia@uri.edu.
authors.forename: Nasser H
authors.initials: NH
authors.lastname: Zawia
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D029561:Lythraceae; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases