Induction of Nrf2/ARE signaling pathway and inhibition of CYP 2A6 and 2E1 by açaí may mediate cytoprotection against oxidative stress

Abstract

Investigation of potential health benefits of açaí (Euterpe olereacea) to deliver effective strategies to treat or mitigate a variety of human ailments requires isolation of bioactive chemical constituents, identification of biological targets and associated molecular mechanisms. Amelioration of oxidative stress (OS) resulting from increased production of reactive oxygen species (ROS) can be achieved by two discrete mechanisms. One mechanism critical to restore cellular homeostasis is the induction of cytoprotective phase II enzymes such as heme oxygenase-01 and NADPH quinone oxidoreductase to eliminate ROS. Induction of such enzymes follows Nrf2/ARE signaling pathway. Besides, inhibition of toxicologically important cytochrome P450 enzymes such as CYP2A6 and CYP2E1 involved in ROS generation presents yet another potential strategy to reduce OS. The current study utilizes a novel bioassay-guided fractionation on açaí berry to study the (a) induction of phase II enzymes in cultured HepG2 cells and (b) inhibition of CYP2A6 and CYP2E1 using human liver microsomes in vitro. Our results indicated the presence of bioactive constituents in açaí with a potential to modulate Nrf2/ARE pathway and subsequent induction of cytoprotective enzymes. Açaí has also been found to have inhibitory constituents towards CYP2A6 and CYP2E1. Interestingly, some fractions were found to be active in both the experimental models indicating possible potentiating or synergistic effect. This study is directed at identification of cytoprotective constituents of açaí and associated mechanisms of action.