Cell experiment:

SK-N-SH cells are seeded at 1.75×104 cells/well in a 24-well plate and cultured overnight. The cells are treated with various concentrations of (+)-DHMEQ (1, 3, and 10 μg/mL) for 24 h and subsequently treated with 300 μM 6-OHDA for 24 h. Then, cells are stained with Trypan blue, and the number of stained cells is counted[1].

(+)-DHMEQ is an activator of antioxidant transcription factor Nrf2. (+)-DHMEQ is the enantiomer of (-)-DHMEQ. (-)-DHMEQ inhibits NF-kB than its enantiomer (+)-DHMEQ.

(+)-DHMEQ ((2R,3R,4R)-DHMEQ) activates Nrf2, which is a transcription factor that induces the expression of multiple antioxidant enzymes. (+)-DHMEQ activates Nrf2 in a promoter reporter assay. (+)-DHMEQ also increases the expression of target antioxidant proteins and cancelled reactive oxygen species (ROS)-induced cell death in a neuronal cell line. ROS generating 6-hydroxydopamine hydrochloride (6-OHDA) induces the death of SK-N-SH cells, and (+)-DHMEQ decreases the cytotoxic effect of 6-OHDA, whereas its effect is weaker in Nrf2-knockdown cells prepared with siRNA. Thus, enhancement of the neural cell viability by (+)-DHMEQ is due to the activation of Nrf2[1].

[1]. Niitsu Y, et al. Chemoenzymatic synthesis of (2R,3R,4R)-dehydroxymethylepoxyquinomicin (DHMEQ), a newactivator of antioxidant transcription factor Nrf2. Org Biomol Chem. 2011 Jun 21;9(12):4635-41.