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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.JN

Abstract

Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (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 the path 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 factor α (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.

Authors+Show Affiliations

Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota, School of Medicine and Health Sciences, Grand Forks, ND, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23468550

Citation

Rojanathammanee, Lalida, et al. "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." The Journal of Nutrition, vol. 143, no. 5, 2013, pp. 597-605.
Rojanathammanee L, Puig KL, Combs CK. 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;143(5):597-605.
Rojanathammanee, L., Puig, K. L., & Combs, C. K. (2013). 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. The Journal of Nutrition, 143(5), 597-605. https://doi.org/10.3945/jn.112.169516
Rojanathammanee L, Puig KL, Combs CK. 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;143(5):597-605. PubMed PMID: 23468550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Rojanathammanee,Lalida, AU - Puig,Kendra L, AU - Combs,Colin K, Y1 - 2013/03/06/ PY - 2013/3/8/entrez PY - 2013/3/8/pubmed PY - 2013/6/19/medline SP - 597 EP - 605 JF - The Journal of nutrition JO - J. Nutr. VL - 143 IS - 5 N2 - Alzheimer disease (AD) brain is characterized by extracellular plaques of amyloid β (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 the path 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 factor α (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. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/23468550/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_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.3945/jn.112.169516 DB - PRIME DP - Unbound Medicine ER -