Cellular oxidative stress is a major cause of illness and death worldwide, and many areturning to Natural Products or Complementary and Alternative Medicines to combat thiscondition. 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 thepathogenic conditions associated with disruptions in redox balance. In addition, the study willidentify biological targets for these constituents, thus providing insight into the mechanism bywhich this ?superfruit? confers these protective efects in humans. An essential element of theproposed study is that undergraduate and Master's level students at The University of NorthCarolina at Greensboro will have opportunities to engage in meaningful scientific research aimedat elucidating details regarding the mechanism of action of one of the most popular anti-oxidantnatural products on the market. The popularity of the Acait has not translated to a wealth ofscientific research regarding its effects, thus the study also fills an important void in science, thatif 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 thatmay 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 batteryof anti-oxidant genes may be turned on in response to cellular signals that report on overall redoxbalance. The methods to be employed include in vitro catalytic assays for the two humancytochrome P450 isozymes, P4502E1 and P4502A6, and a luciferase-based cell culture system inwhich 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 genetranscription. Elements of this type are present in a large number of human genes associatedwith anti-oxidant functions. The process of fractionation and isolation of the individualconstituents used in each of the different assays will be guided by the observed activitiesassociated with each different fraction, and modern methods of NMR and Mass Spectralcharacterization will be used to determine the chemical identity of the active constituents.
The proposed project will examine the biochemical effects that give rise to the observedbeneficial health effects of the very popular acai berry products. The research willaddress the anti-oxidant properties of the berry; along with identification of chemicalcomponents of the berry that confer health benefits to the consumer. Understanding thesemechanisms is a critical component to the development of effective strategies to treat orprevent a variety of human health problems using this product.
|Badal, Simone A M; Asuncion Valenzuela, Malyn M; Zylstra, Dain et al. (2017) Glaucarubulone glucoside from Castela macrophylla suppresses MCF-7 breast cancer cell growth and attenuates benzo[a]pyrene-mediated CYP1A gene induction. J Appl Toxicol 37:873-883|
|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|