Induction of Nrf2 activity by Daucus carota subsp. maximus: bioassay-guided isolation of chrysoeriol, luteolin 7-O-glucoside and eugenin as active compounds.

OBJECTIVES

To investigate the Nrf2 activity-inducing property of Daucus carota subsp. maximus and to isolate the bioactive compounds responsible for this.

METHODS

The cell viability (MTT) assay was performed using the AREc32 cell line to determine non-cytotoxic concentrations of the test samples. Subsequently, a luciferase reporter gene assay was conducted with these non-toxic concentrations in AREc32 cells to evaluate the induction of the cellular antioxidant defence system through activation of the Nrf2 transcription factor. Bioactive compounds were then isolated from the active fractions by HPLC, and their structures elucidated using spectroscopic techniques.

KEY FINDINGS: The active methanolic extract was subjected to bioassay-guided fractionation, yielding five compounds: apigenin (1), chrysoeriol (2), luteolin (3), luteolin 7-O-glucoside (4), and eugenin (5). Among these, compounds 24, and 5 exhibited more than a two-fold induction of Nrf2 activity, indicating their potential as cancer chemopreventive agents. Notably, eugenin (5) demonstrated the highest potency, inducing Nrf2 activity by 8.1-fold.

CONCLUSIONS

The high level of Nrf2 induction and simple chemical structure suggested that eugenin (5) could be a suitable candidate for generating synthetic analogues to develop new cancer chemopreventive agents.