Michael acceptors LigC and LigF modulate NQO1 through different mechanisms based on the in vitro observations. The left side clear arrow with black borders shows the inhibitory effect of LicA on AhR pathway. The blue arrow shows the effect of LicA on Keap1-Nrf2 pathway and the induction of ARE and NQO1 by this compound. Pink arrow shows the effect of LigC on Keap1-Nrf2 pathway and the induction of ARE and NQO1 by this compound.
LigC interacts with Keap1 and the consequent translocation of Nrf2 to the nucleus and its interaction with ARE might result in NQO1 induction. LicA could influence the induction of NQO1 through two parallel, yet opposing molecular interactions at the promoter of NQO1. It can increase ARE induction through interacting with Keap1 and decrease XRE induction through inhibiting AhR, which might result in a lower NQO1 induction compared to that of LigC.