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 Mart. (Arecaceae)) 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 thes constituents, thus providing insight into the mechanism by which this "super fruit" confers these protective effects in humans. The popularity of the Acai has not translated to a wealth of scientific research regarding its effects, thus the study also fills an important void in science, hat if filled could greatly enhance efforts to capitalize on the health benefits of this product. 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 long terms goals for the project are to provide scientific knowledge concerning mode of action of acai products in reducing cellular oxidative stress, and improving human health. The two main aims of this study are to demonstrate that chemical constituents of the acai (1) inhibit cytochrome P450 enzymes that initiate production of reactive chemical species, including reactive oxygen species (ROS), and (2) induce the Nrf2-dependent transcriptional pathway, activating an entire battery of anti-oxidant genes. An additional component of Aim 2 is to demonstrate that components of the acai act synergistically to bring about increased antioxidant gene expression. 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 o this type are present in a large number of human genes associated with anti-oxidant functions. Activity-guided fractionation and synergy-guided fractionation will be used to isolate active components of the acai and modern methods of NMR and mass spectral characterization will be used to determine their chemical identity.
The proposed project will examine the biochemical effects that give rise to the observed beneficial health effects of the very popular acai berry products. The research will address the anti-oxidant properties of the berry, along with identification of chemical components of the berry that confer health benefits to the consumer. Understanding these mechanisms is a critical component to the development of effective strategies to treat or prevent a variety of human health problems using this product.
|Kandagatla, Suneel K; Mack, Todd; Simpson, Sean et al. (2014) Inhibition of human cytochrome P450 2E1 and 2A6 by aldehydes: structure and activity relationships. Chem Biol Interact 219:195-202|