Nrf2 induction potency of plant-derived compounds demonstrated by an ARE luciferase reporter and conventional assay of NAD(P) H-quinone acceptor oxidoreductase 1 activity

Abstract Objective Various plants have been reported to contain compounds that promote the nuclear accumulation of Nrf2 to induce a set of xenobiotic detoxifying enzymes such as NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) via antioxidant response element (ARE). While conventional methods for evaluating the Nrf2 induction potency of compounds include NQO1 activity, recently, an ARE luciferase reporter was developed to directly assess the Nrf2 induction potency of compounds of interest. In this study, the ability of these two assays to evaluate and determine Nrf2 induction potency of plant-derived compounds was compared. Results Although the compounds overall showed a high degree of consistency between the assays, several compounds did not. The results suggest that although the NQO1 assay can be used as an evaluation method to estimate the Nrf2 induction potency of a compound, an ARE luciferase reporter may offer greater precision. In summary, the inconsistency in Nrf2 induction potency evaluated by the reporter and NQO1 assays for some of the plant-derived compounds evaluated herein, including resveratrol, may be due to a variety of factors that regulate NQO1 expression and activity other than Nrf2, with each compound having a different degree of effect on these factors.