Nrf2/ARE

CDDO-EA potently activates Nrf2/ARE in a cell culture model of ALS and in the G93A SOD1 mouse model of ALS. CDDO-EA is a potent inducer of apoptosis in A549 lung cancer cells, as shown both by PARP cleavage and Annexin staining. CDDO-EA is more potent than CDDO itself as inducers of heme oxygenase-1 (HO-1). In RAW264.7 macrophage-like cells, CDDO-EA is 7-fold more potent than CDDO as suppressors of the ability of IFN-γ to induce iNOS.

The survival analysis shows that G93A mice treated with CDDO-EA, compared to G93A littermate controls, lives significantly longer. CDDO-EA treatment increases the life-span by 20.6 days from 124.05±3.7 days to 144.72±8.1 days (16.6%) (p<0.001). In CDDO-EA-treated G93A mice, the age of death is 141.4±5.2 days and the duration from the age of onset to the age of death is 57.6±7.6 days, which means that the age of death from onset is prolonged by 17.5 days (43%).