Nrf2 induction potency of plant-derived compounds determined using an antioxidant response element luciferase reporter and conventional NAD(P)H-quinone acceptor oxidoreductase 1 activity assay

Erina Tamaru; Daichi Kokubu; Yusuke Ushida; Ken Itoh

Nrf2 induction potency of plant-derived compounds determined using an antioxidant response element luciferase reporter and conventional NAD(P)H-quinone acceptor oxidoreductase 1 activity assay

2024

Erina Tamaru | Daichi Kokubu | Yusuke Ushida | Ken Itoh

Abstract Objective Various plants have been reported to contain compounds that promote the transcriptional activity of Nuclear factor erythroid 2-related factor 2 (Nrf2) to induce a set of xenobiotic detoxifying enzymes, such as NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1), via the antioxidant response element (ARE). While conventional methods for evaluating Nrf2 induction potency include measurement of NQO1 activity, an ARE luciferase reporter assay was recently developed to specifically assess Nrf2 induction potency of compounds of interest. In this study, we compared the abilities of these two assays to evaluate and determine Nrf2 induction potency of plant-derived compounds. Results Although the compounds exhibited a high degree of consistency between assays, several compounds did not. These results suggest that although the NQO1 assay can be used as an evaluation method to estimate Nrf2 induction potency of a compound, an ARE luciferase reporter approach may offer greater precision. In summary, inconsistency in Nrf2 induction potency evaluated by the reporter and NQO1 assays of plant-derived compounds, including resveratrol, may be due to a variety of factors that may regulate NQO1 gene expression other than Nrf2 and/or directly modulate NQO1 enzymatic activity or protein levels, with each compound having a different degree of effect on these factors.

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