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United States Department of Agriculture

Agricultural Research Service

Title: Cellular and Behavioral Effects of Stilbene Resveratrol Analogs: Implications for Reducing the Deleterious Effects of Aging

Authors
item Joseph, James
item FISHER, DEREK
item Cheng, Vivian - TUFTS UNIVERSITY
item Rimando, Agnes - USDA/ARS
item SHUKITT-HALE, BARBARA

Submitted to: Journal of Agriculture and Food Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 24, 2008
Publication Date: November 26, 2008
Citation: Joseph, J.A., Fisher, D.R., Cheng, V., Rimando, A.M., Shukitt Hale, B. 2008. Cellular and Behavioral Effects of Stilbene Resveratrol Analogs: Implications for Reducing the Deleterious Effects of Aging. Journal of Agriculture and Food Chemistry.56(22)10544-10551.

Interpretive Summary: There is a plethora of research that suggests that polyphenolic compounds contained in fruits and vegetables that are rich in color may have potent antioxidant and anti-inflammatory abilities. In several previous studies, we found that blueberry extract significantly attenuated age-related motor and cognitive deficits that were associated with brain aging. However, it is difficult to discern from a blueberry extract the contribution of non-polypholics such as sugars, organic acids, etc. to these effects. One particular group of compounds that may be responsible for these effects and that has received a great deal of attention are the stilbenes, which have potent antioxidant activity and are found in berries and red grapes. Thus the present studies were carried out to determine if these compounds would be efficacious in reversing the deleterious effects of aging on cognitive and motor behaviors in aged rats. We have previously shown that some cells are sensitive to oxidative stress; in Experiment I we utilized resveratrol, a stilbene, and six other similar compounds and examined their efficacies in preventing decrements in those cells. In Experiment II, we utilized one of more efficacious analogs (pterostilbene) from Experiment I and added a low or a high concentration of pterostilbene to a diet which was fed to the aged rats. Results indicated that pterostilbene was effective in reversing both motor and cognitive behavioral deficits and short-term memory was correlated with pterostilbene levels in the brain. These results are discussed in terms of reductions in oxidative stress and increases in brain cell signaling that might be responsible for the beneficial effects in aging.

Technical Abstract: There is a plethora of research that suggests that polyphenolic compounds contained in fruits and vegetables that are rich in color may have potent antioxidant and anti-inflammatory activities. In several previous studies, we found that crude blueberry (BB) extract significantly attenuated age-related motor and cognitive deficits that were associated with a reversal of several neuronal parameters related to brain aging (e.g., reduced receptor sensitivity). However, it is difficult to discern from a crude BB extract the contribution of non-polyphenolics (sugars, organic acids, etc.) to these effects. One particular group of compounds that may be responsible for these effects and that has received a great deal of attention are the stilbenes (e.g., resveratrol), which have potent antioxidant activity and are found in berries and red grapes. Thus, the present studies were carried out to determine if these compounds would be efficacious in reversing the deleterious effects of aging on cognitive and motor behaviors, as well as dopamine release (a marker of muscarinic receptor integrity), in 19 mo Fischer 344 rats. These determinations were made by first utilizing resveratrol and 6 resveratrol analogs (Experiment I) and examining their efficacies in preventing dopamine (DA)-induced decrements in calcium clearance following oxotremorine-induced depolarization in COS-7 cells transfected with M1 muscarinic receptors (MAChR) that we have shown previously to be sensitive to oxidative stressors. In Experiment II, we utilized one of the more efficacious analogs (pterostilbene) from Experiment I and added a low (0.004%) or a high (0.016%) concentration of pterostilbene to an NIH 31 diet which was fed to the aged rats. Results indicated that pterostilbene was effective in reversing both motor and cognitive behavioral deficits, as well as DA release, and working memory was correlated with pterostilbene levels in the hippocampus. These results are discussed in terms of reductions in oxidative stress and increases in neuronal signaling that might be responsible for the beneficial effects in aging.

Last Modified: 9/10/2014