Location: Boston, Massachusetts2013 Annual Report
1a. 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.
1b. 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.
3. Progress Report:
Açai 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 açai-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.