Pomegranate polyphenols and extract inhibit nuclear factor of activated T-cell activity and microglial activation in vitro and in a transgenic mouse model of Alzheimer disease.
J Nutr. 2013 May ;143(5):597-605. Epub 2013 Mar 6. PMID: 23468550
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND, USA.
Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloidβ (Aβ) peptide with reactive microglia. This study aimed to determine whether a dietary intervention could attenuate microgliosis. Memory was assessed in 12-mo-old male amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice via Barnes maze testing followed by division into either a control-fed group provided free access to normal chow and water or a treatment group provided free access to normal chow and drinking water supplemented with pomegranate extract (6.25 mL/L) for 3 mo followed by repeat Barnes maze testing for both groups. Three months of pomegranate feeding decreased thepath length to escape of mice compared with their initial 12-mo values (P<0.05) and their control-fed counterparts (P<0.05). Brains of the 3-mo study pomegranate-fed mice had lower tumor necrosis factorα (TNF-α) concentrations (P<0.05) and lower nuclear factor of activated T-cell (NFAT) transcriptional activity (P<0.05) compared with controls. Brains of the 3-mo pomegranate or control mice were also compared with an additional control group of 12-mo-old mice for histologic analysis. Immunocytochemistry showed that pomegranate- but not control-fed mice had attenuated microgliosis (P<0.05) and Aβ plaque deposition (P<0.05) compared with 12-mo-old mice. An additional behavioral study again used 12-mo-old male APP/PS1 mice tested by T-maze followed by division into a control group provided with free access to normal chow and sugar supplemented drinking water or a treatment group provided with normal chow and pomegranate extract-supplemented drinking water (6.25 mL/L) for 1 mo followed by repeat T-maze testing in both groups. One month of pomegranate feeding increased spontaneous alternations versus control-fed mice (P<0.05). Cell culture experiments verified that 2 polyphenol components of pomegranate extract, punicalagin and ellagic acid, attenuated NFAT activity in a reporter cell line (P<0.05) and decreased Aβ-stimulated TNF-α secretion by murine microglia (P<0.05). These data indicate that dietary pomegranate produces brain antiinflammatory effects that may attenuate AD progression.