Progress 10/01/12 to 09/30/13
Outputs
Progress Report Objectives (from AD-416): In Phase I of this study we will assess various acai berry preparations and compare these with concord grape juice, pomegranate juice and white grape juice to determine if they have similar effects to those previously seen with blueberries. If the acai berry preparations are effective, then two more Phases (II, III) of will be carried out to determine the mechanisms involved in the beneficial effects of these extracts on behavior by assessing alterations in neuronal signaling and autophagy. The third goal of this project will be to determine the effects of the most effective extracts on age-related differences in resistance to oxidative stress/inflammation (OS/INF) by exposing young and old animals to lipopolysaccharide (LPS) an inflammatory agent. Approach (from AD-416): In this project we are attempting to investigate the antioxidant anti- inflammatory properties of the acai berry preparations. In Phase 1 of the proposal, the goal is to use freeze dried acai (AC) berries, fresh acai berries, Acai spray dried berries and compare these to concord grape juice, pomegranate juice, white grape juice and california dried plum juice (prune juice and various permutations and combinations of one - seven) to see if they have similar effects to those that we have seen with blueberry (BB) and other berry extracts and juices in cell signaling and to what degree. The specific goals are: 1. Determine the juices that would contribute to reductions in calcium clearance (following depolarization), and oxidant stress (amyloid beta, A(beta)42- induced) or inflammatory (lipolysaccaride, LPS) signaling in mixed glial/primary hippocampal cultures. These treatments will be compared to those of vitamin E, and the NSAID, piroxicam and the eroxisome proliferatoractivated receptor (PPAR gamma) agonist, rosiglitazone against A(beta)42 or LPS treatment. 2. Assess whether the putative beneficial effects on the cells of the ME would involve alterations in stress (e.g., p38 mitogen activated protein kinase, MAPK) signaling, as well as activation of protective signals (e.g. , insulin growth factor-1, IGF-1). 3. Determine the stress signal responses of the various mixes in BV-2 mouse microglial cells that are exposed to LPS after treatment with the various extracts. We will purchase the hippocampal cells and the supplies (e.g., antibodies for the stress signals, media, etc) to carry out the cells studies. In Phase II, we propose to assess and compare the benefits of consumption of two different species of acai for improving cognitive and motor function in aging. Specifically, we will assess the efficacy of two different freeze dried acai preparations: 1) acai pulp Euterpe oleracea Mart., EO and 2) acai pulp Euterpe precatoria Mart., DP on the behavior of aged rats. We feel it is necessary to look at the whole fruit before fractionating the berry. In addition, cell studies we are currently conducting using the fractions of the acai berry are not showing any one fraction to be the �most effective� fraction on all of our endpoints. We will then develop mechanistic interpretations of the positive benefits of the acai berry, by assessing the autophagy function (a process involving the recycling and degradation of cellular debris) and signaling pathways. Autophagy, a process involving the recycling and degradation of cellular debris, is a more relevant marker for us to measure. A�ai is a black-purple fruit cultivated in the Amazon delta, Brazil and Bolivia. In phase I of the study, we have investigated the bioactive profiles of acai whole fruits as well as different phenolic fractions. Furthermore, the studies were also conducted to explore the effects of acai fruit pulp extracts on restoration of autophagy (the process of clearing toxic proteins in the brain), which was chemically blocked by certain known inhibitors. The results indicated substantial recovery and clearance of toxic accumulations by acai in brain cells in culture. The first peer-reviewed manuscript was published in the Journal of Agriculture and Food Chemistry, and the second one has been submitted for publication. In Phase II of the study, 19 month old rats were fed one of two diets containing 2% acai fruit pulp [Euterpe oleracea Mart. (EO) or Euterpe precatoria Mart. (EP)] or a control diet. Behavior and neurocognitive function were then assessed after rats consumed the diets for 8 weeks. Both the EO and EP diet improved working memory, relative to controls; however, only the EO diet improved reference memory. Subsequently, mouse microglial cells (BV2) were treated with serum collected from the rats, prior to an inflammatory challenge. Cells treated with serum from a�ai-fed rats showed reductions in two biomarkers of inflammation, and reductions in these markers correlated with improved behavior in the rats. Additional biomarkers are currently being measured.
Impacts
(N/A)
Publications
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Progress 10/01/11 to 09/30/12
Outputs
Progress Report Objectives (from AD-416): In Phase I of this study we will assess various acai berry preparations and compare these with concord grape juice, pomegranate juice and white grape juice to determine if they have similar effects to those previously seen with blueberries. If the acai berry preparations are effective, then two more Phases (II, III) of will be carried out to determine the mechanisms involved in the beneficial effects of these extracts on behavior by assessing alterations in neuronal signaling and autophagy. The third goal of this project will be to determine the effects of the most effective extracts on age-related differences in resistance to oxidative stress/inflammation (OS/INF) by exposing young and old animals to lipopolysaccharide (LPS) an inflammatory agent. Approach (from AD-416): In this project we are attempting to investigate the antioxidant anti- inflammatory properties of the acai berry preparations. In Phase 1 of the proposal, the goal is to use freeze dried acai (AC) berries, fresh acai berries, Acai spray dried berries and compare these to concord grape juice, pomegranate juice, white grape juice and california dried plum juice (prune juice and various permutations and combinations of one - seven) to see if they have similar effects to those that we have seen with blueberry (BB) and other berry extracts and juices in cell signaling and to what degree. The specific goals are: 1. Determine the juices that would contribute to reductions in calcium clearance (following depolarization), and oxidant stress (amyloid beta, A(beta)42- induced) or inflammatory (lipolysaccaride, LPS) signaling in mixed glial/primary hippocampal cultures. These treatments will be compared to those of vitamin E, and the NSAID, piroxicam and the eroxisome proliferatoractivated receptor (PPAR gamma) agonist, rosiglitazone against A(beta)42 or LPS treatment. 2. Assess whether the putative beneficial effects on the cells of the ME would involve alterations in stress (e.g., p38 mitogen activated protein kinase, MAPK) signaling, as well as activation of protective signals (e.g. , insulin growth factor-1, IGF-1). 3. Determine the stress signal responses of the various mixes in BV-2 mouse microglial cells that are exposed to LPS after treatment with the various extracts. We will purchase the hippocampal cells and the supplies (e.g., antibodies for the stress signals, media, etc) to carry out the cells studies. In Phase II, we propose to assess and compare the benefits of consumption of two different species of acai for improving cognitive and motor function in aging. Specifically, we will assess the efficacy of two different freeze dried acai preparations: 1) acai pulp Euterpe oleracea Mart., EO and 2) acai pulp Euterpe precatoria Mart., DP on the behavior of aged rats. We feel it is necessary to look at the whole fruit before fractionating the berry. In addition, cell studies we are currently conducting using the fractions of the acai berry are not showing any one fraction to be the �most effective� fraction on all of our endpoints. We will then develop mechanistic interpretations of the positive benefits of the acai berry, by assessing the autophagy function (a process involving the recycling and degradation of cellular debris) and signaling pathways. Autophagy, a process involving the recycling and degradation of cellular debris, is a more relevant marker for us to measure. In phase I of the study, we have investigated the bioactive profiles of acai whole fruits as well as different phenolic fractions. Comparisons with some of the commonly known fruits indicate that acai fruit contains substantially higher amounts of certain phenolic bioactive compounds. Biological activity assessment of this fruit pulp on brain cells grown in culture has shown protective and rescuing effects when the cells were chemically stressed. Treating the cells prior to stress resulted in rescue from lethal effects of lipopolysaccharide (LPS), through maintaining calcium homeostasis and enhancing inter-neuronal protective signals as well as suppression of inflammatory and oxidative mediators of aging at the cellular level. Furthermore, the studies were also conducted to explore the effects of acai fruit pulp extracts on restoration of autophagy, which was chemically blocked by certain known inhibitors. The results indicated substantial recovery and clearance of toxic accumulations in the brain cells in culture. The first peer-reviewed manuscript was published in the Journal of Agriculture and Food Chemistry and the second one is in preparation. Phase II of the study, exploring the differential effects of two species of acai fruit pulp diets (2%) on behavior and neurocognitive function, is currently in progress. The behavioral analysis of the rats fed with acai diet has been completed and the results are being compiled. Preliminary findings indicate certain cognitive/behavioral benefits with acai diet supplementation. The effect of acai in establishing inter-brain cell communication signals is being currently evaluated in the brains of rats fed with these diets.
Impacts
(N/A)
Publications
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Progress 10/01/10 to 09/30/11
Outputs
Progress Report Objectives (from AD-416) In Phase I of this study we will assess various acai berry preparations and compare these with concord grape juice, pomegranate juice and white grape juice to determine if they have similar effects to those previously seen with blueberries. If the acai berry preparations are effective, then two more Phases (II, III) of will be carried out to determine the mechanisms involved in the beneficial effects of these extracts on behavior by assessing alterations in neuronal signaling and autophagy. The third goal of this project will be to determine the effects of the most effective extracts on age-related differences in resistance to oxidative stress/inflammation (OS/INF) by exposing young and old animals to lipopolysaccharide (LPS) an inflammatory agent. Approach (from AD-416) In this project we are attempting to investigate the antioxidant anti- inflammatory properties of the acai berry preparations. In Phase 1 of the proposal, the goal is to use freeze dried acai (AC) berries, fresh acai berries, Acai spray dried berries and compare these to concord grape juice, pomegranate juice, white grape juice and california dried plum juice (prune juice and various permutations and combinations of one - seven) to see if they have similar effects to those that we have seen with blueberry (BB) and other berry extracts and juices in cell signaling and to what degree. The specific goals are: 1. Determine the juices that would contribute to reductions in calcium clearance (following depolarization), and oxidant stress (amyloid beta, A(beta)42- induced) or inflammatory (lipolysaccaride, LPS) signaling in mixed glial/primary hippocampal cultures. These treatments will be compared to those of vitamin E, and the NSAID, piroxicam and the eroxisome proliferatoractivated receptor (PPAR gamma) agonist, rosiglitazone against A(beta)42 or LPS treatment. 2. Assess whether the putative beneficial effects on the cells of the ME would involve alterations in stress (e.g., p38 mitogen activated protein kinase, MAPK) signaling, as well as activation of protective signals (e.g. , insulin growth factor-1, IGF-1). 3. Determine the stress signal responses of the various mixes in BV-2 mouse microglial cells that are exposed to LPS after treatment with the various extracts. We will purchase the hippocampal cells and the supplies (e.g., antibodies for the stress signals, media, etc) to carry out the cells studies. In Phase II, we propose to assess and compare the benefits of consumption of two different species of acai for improving cognitive and motor function in aging. Specifically, we will assess the efficacy of two different freeze dried acai preparations: 1) acai pulp Euterpe oleracea Mart., EO and 2) acai pulp Euterpe precatoria Mart., DP on the behavior of aged rats. We feel it is necessary to look at the whole fruit before fractionating the berry. In addition, cell studies we are currently conducting using the fractions of the acai berry are not showing any one fraction to be the �most effective� fraction on all of our endpoints. We will then develop mechanistic interpretations of the positive benefits of the acai berry, by assessing the autophagy function (a process involving the recycling and degradation of cellular debris) and signaling pathways. Autophagy, a process involving the recycling and degradation of cellular debris, is a more relevant marker for us to measure. The acai berry fruit extracts were fractionated based on their polyphenolic content, and different fractions were tested for their efficacy in maintaining calcium homeostasis when the membranes of brain cells (astrocytes and neurons) were chemically depolarized. Pretreatment with acai berry pulp extracts significantly sequestered the calcium influx induced by lipopolysaccharide (LPS) when compared to that of control. The relative effects were higher in astrocytes (glia) than neurons when the effects were measured after co-culturing glia with neurons, similar to the condition observed in brain. These results offer a unique perspective on the astrocyte-derived protection of neurons from calcium imbalance, since astrocytes are typically thought to activate proinflammatory and stress signals that can harm neurons. Further studies were conducted to explore the molecular effects of acai pulp extracts in the attenuation of oxidative stress and inflammation using BV2 microglial cells. Acai pulp fractions with varied polyphenolic contents significantly reduced nitrite production induced by LPS, which was correlated with a significant concentration-dependent decrease in iNOS expression, a proinflammatory enzyme. The protection of microglial cells by acai pulp extracts was also accompanied by the significant concentration-dependent reduction in inflammatory mediators such as cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (p38-MAPK), tumor necrosis factor-alpha (TNFa) and nuclear factor kappa-b (NF-�B), indicating reductions in stress-mediated signaling, one mechanism to combat some of the inflammatory and oxidative mediators of aging at the cellular level. To explore whether mitigation of oxidative stress and inflammation by acai pulp extracts contribute to the survival of neurons under stress conditions, we used HT22 hippocampal neurons and assessed markers of autophagy, a process by which toxic debris is recycled and cleared in neurons. Pretreatment with acai fruit extracts enhanced the restoration of autophagy function, measured by several different markers. These results demonstrate the benefits of acai fruit on neuroprotection beyond the traditionally known antioxidant effects. We are now writing two manuscripts detailing these results.
Impacts
(N/A)
Publications
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Progress 10/01/09 to 09/30/10
Outputs
Progress Report Objectives (from AD-416) In Phase I of this study we will assess various acai berry preparations and compare these with concord grape juice, pomegranate juice and white grape juice to determine if they have similar effects to those previously seen with blueberries. If the acai berry preparations are effective, then two more Phases (II, III) of will be carried out to determine the mechanisms involved in the beneficial effects of these extracts on behavior by assessing alterations in neuronal signaling and neurogenesis. The third goal of this project will be to determine the effects of the the most effective extracts on age-related differences in resistance to oxidative stress/inflammation (OS/INF) by exposing young and old animals to lipopolysaccharide (LPS) an inflammatory agent. Approach (from AD-416) In this project we are attempting to investigate the antioxidant anti- inflammatory properties of the acai berry preparations. In Phase 1 of the proposal, the goal is to use freeze dried acai (AC) berries, fresh acai berries, Acai spray dried berries and compare these to concord grape juice, pomegranate juice, white grape juice and california dried plum juice (prune juice and various permutations and combinations of one - seven) to see if they have similar effects to those that we have seen with blueberry (BB) and other berry extracts and juices in cell signaling and to what degree. The specific goals are: 1. Determine the juices that would contribute to reductions in calcium clearance (following depolarization), and oxidant stress (amyloid beta, A(beta)42- induced) or inflammatory (lipolysaccaride, LPS) signaling in mixed glial/primary hippocampal cultures. These treatments will be compared to those of vitamin E, and the NSAID, piroxicam and the eroxisome proliferatoractivated receptor (PPAR gamma) agonist, rosiglitazone against A(beta)42 or LPS treatment. 2. Assess whether the putative beneficial effects on the cells of the ME would involve alterations in stress (e.g., p38 mitogen activated protein kinase, MAPK) signaling, as well as activation of protective signals (e.g. , insulin growth factor-1, IGF-1). 3. Determine the stress signal responses of the various mixes in BV-2 mouse microglial cells that are exposed to LPS after treatment with the various extracts. We will purchase the hippocampal cells and the supplies (e.g., antibodies for the stress signals, media, etc) to carry out the cells studies. In this project we are attempting to investigate the antioxidant anti- inflammatory properties of acai berry fractions. Inflammation and oxidative stress on brain cells set off a cascade of events resulting in death of neurons, ultimately leading to declines in cognitive and motor functions as well as age-related diseases. Loss of cognitive function with aging has been related to loss of regulation in calcium (Ca2+) balance inside the brain cells. We have shown that these insults on brain cells can be prevented with the consumption of other berry fruits as evident in our previous studies on aged animals. These fruits are packed with an array of polyphenolic compounds which have the ability to reduce stress and inflammation. To demonstrate the mechanism by which berry fruit extracts assist in weakening the stress insults, we used brain cells which were treated with different fractions of acai berry extracts, containing different classes of phytonutrients such as anthocyanins, flavanoids, terpinoids, etc., and subjected to stress. The acai pulp extracts increased calcium recovery in the cells and protected the cells from nitrite stress. The results indicate that components of acai berries, like the other berries we tested, are effective against inflammatory and oxidative stress in the brain cells. We also showed that acai berry extracts were able to rescue neurons through induction of autophagy, a process by which toxic debris is recycled and cleared in neurons. This is important since if the neuronal cell�s ability to clean up and remove toxic debris is antagonized by oxidative or inflammatory stressors, the cell may lose viability and show declines in function. The finding that acai berry extract pre-treatments can mitigate these effects has important implications for preventing declines in neuronal function via nutrition. Monitoring of this project is accomplished through e-mail and/or teleconference.
Impacts
(N/A)
Publications
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