Friday, November 22, 2024
11/22/2024
Abstract: Cellular oxidative stress is a major cause of illness and death worldwide, and many are turning to Natural Products or Complementary and Alternative Medicines to combat this condition. The current study is intended to identify constituents in the very popular Acai berry (Euterpe Oleracea) with the potential to reduce oxidative stress, thereby preventing the pathogenic conditions associated with disruptions in redox balance. In addition, the study will identify biological targets for these constituents, thus providing insight into the mechanism by which this “superfruit” confers these protective efects in humans. An essential element of the proposed study is that undergraduate and Master's level students at The University of North Carolina at Greensboro will have opportunities to engage in meaningful scientific research aimed at elucidating details regarding the mechanism of action of one of the most popular anti-oxidant natural products on the market. The popularity of the Acait has not translated to a wealth of scientific research regarding its effects, thus the study also fills an important void in science, that if filled could greatly enhance efforts to capitalize on the health benefits of this product. The two main targets to be explored in this study are (1) Cytochrome P450 enzymes that may be able to initiate production of reactive chemical species, including reactive oxygen species (ROS), and (2) the Nrf2-dependent transcriptional regulatory pathway by which an entire battery of anti-oxidant genes may be turned on in response to cellular signals that report on overall redox balance. The methods to be employed include in vitro catalytic assays for the two human cytochrome P450 isozymes, P4502E1 and P4502A6, and a luciferase-based cell culture system in which a reporter plasmid containing a genetic element called an “antioxidant response element” will be used to assess the ability of constituents in the acai berry extract to up-regulate gene transcription. Elements of this type are present in a large number of human genes associated with anti-oxidant functions. The process of fractionation and isolation of the individual constituents used in each of the different assays will be guided by the observed activities associated with each different fraction, and modern methods of NMR and Mass Spectral characterization will be used to determine the chemical identity of the active constituents.
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