Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease

Hartman, Richard E.; Shah, Aartie; Fagan, Anne M.; Schwetye, Katherine E.; Parsadanian, Maia; Schulman, Risa; Finn, Mary Beth; Holtzman, David M.

doi:10.1016/j.nbd.2006.08.006

Cited by 299 publications

(186 citation statements)

References 61 publications

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“…Anti-ROS agents, including curcumin and phenyl-N-tert-butyl nitrene, reduce parenchymal amyloid burden in aged APP mice (60)(61)(62)(63). Other anti-ROS agents, however, are not effective (20,36,64).…”

Section: Discussionmentioning

confidence: 99%

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Han

Zhou

Johnson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid β peptide (Aβ) within walls of cerebral arteries and is an important cause of intracerebral hemorrhage, ischemic stroke, and cognitive dysfunction in elderly patients with and without Alzheimer's Disease (AD). NADPH oxidase-derived oxidative stress plays a key role in soluble Aβ-induced vessel dysfunction, but the mechanisms by which insoluble Aβ in the form of CAA causes cerebrovascular (CV) dysfunction are not clear. Here, we demonstrate evidence that reactive oxygen species (ROS) and, in particular, NADPH oxidase-derived ROS are a key mediator of CAA-induced CV deficits. First, the NADPH oxidase inhibitor, apocynin, and the nonspecific ROS scavenger, tempol, are shown to reduce oxidative stress and improve CV reactivity in aged Tg2576 mice. Second, the observed improvement in CV function is attributed both to a reduction in CAA formation and a decrease in CAA-induced vasomotor impairment. Third, anti-ROS therapy attenuates CAA-related microhemorrhage. A potential mechanism by which ROS contribute to CAA pathogenesis is also identified because apocynin substantially reduces expression levels of ApoE-a factor known to promote CAA formation. In total, these data indicate that ROS are a key contributor to CAA formation, CAA-induced vessel dysfunction, and CAA-related microhemorrhage. Thus, ROS and, in particular, NADPH oxidase-derived ROS are a promising therapeutic target for patients with CAA and AD.Alzheimer's disease | cerebral amyloid angiopathy | reactive oxygen species | NADPH oxidase | vasomotor dysfunction

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Section: Discussionmentioning

confidence: 99%

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Han

Zhou

Johnson

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

109

100

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“…Several researchers have shown that certain flavanoid-rich foods enhance learning; however, these studies were often performed in aged animals or transgenic mouse models for neurodegenerative disease (Joseph et al, 1999;Hartman et al, 2006). In this context, a dietary intervention study using flavonoid-rich pomegranate juice was not effective in wild-type animals (Hartman et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In cell culture, flavanols have neuroprotective (Reznichenko et al, 2005), anti-oxidant, and antiapoptotic properties (Schroeter et al, 2001;Koh et al, 2004). In vivo, flavanol-rich green tea (Haque et al, 2006), blueberries (Joseph et al, 1999), pomegranates (Hartman et al, 2006), and strawberries enhance memory and synaptic plasticity (Maher et al, 2006). However, the active components of these flavonoidrich foods remain undefined.…”

Section: Introductionmentioning

confidence: 99%

Plant-Derived Flavanol (−)Epicatechin Enhances Angiogenesis and Retention of Spatial Memory in Mice

et al. 2007

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Diet and exercise have a profound impact on brain function. In particular, natural nutrients found in plants may influence neuronal survival and plasticity. Here, we tested whether consumption of a plant-derived flavanol, (Ϫ)epicatechin, enhances cognition in sedentary or wheel-running female C57BL/6 mice. Retention of spatial memory in the water maze was enhanced by ingestion of (Ϫ)epicatechin, especially in combination with exercise. Improved spatial memory was associated with increased angiogenesis and neuronal spine density, but not newborn cell survival, in the dentate gyrus of the hippocampus. Moreover, microarray analysis showed upregulation of genes associated with learning and downregulation of markers of neurodegeneration in the hippocampus. Together, our data show that ingestion of a single flavanol improves spatial memory retention in adult mammals.

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“…Porém, quando em concentração excedente ao normal, essas espécies podem causar duas categorias de efeitos potencialmente importantes: a) danos celulares, ao atacar membranas, proteínas, polissacarídeos e ácidos nucleicos, com consequente alteração funcional e prejuízo das funções vitais em diversos tecidos -adiposo, vascular e cerebral, e órgãos, como músculo e fígado, 8 ocasionando eventualmente algumas doenças, 3,9-11 e b) ativação de caminhos de sinalização específicos. 4,12,13 Estudos epidemiológicos têm mostrado que dietas ricas em frutas e verduras estão associadas a uma menor incidência de doenças crô-nicas e degenerativas, [14][15][16][17][18] embora prova definitiva de que suplementos antioxidantes possam prevenir doenças crônicas não tenha sido obtida ou consistentemente suportada pelos testes de intervenção encontrados na literatura. Há muita controvérsia nessa área de pesquisa, indicando a necessidade de obtenção de evidências inequívocas a respeito da eficácia, segurança e dosagem apropriada de antioxidantes em relação a doenças crônicas.…”

Section: Introductionunclassified

Fontes vegetais naturais de antioxidantes

et al. 2009

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Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease

Cited by 299 publications

References 61 publications

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice

Plant-Derived Flavanol (−)Epicatechin Enhances Angiogenesis and Retention of Spatial Memory in Mice

Fontes vegetais naturais de antioxidantes

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