It is evident that activation of ARE-regulated genes contributes to the regulation of cellular antioxidant defense systems, and pharmacological activation of endogenous cytoprotective proteins through ARE activation is predicted to serve as a novel strategy for the treatment of cardiovascular and inflammatory diseases. Thus, BTZO-1 derivatives appear to have therapeutic potential for a broad range of diseases caused by oxidative stress. In fact, BTZO-2, an active BTZO-1 derivative of ARE activation, confers protection to heart tissues during ischemia/reperfusion injury in rats. Evaluation of the effects of BTZO-1 derivatives on other oxidative stress-related disease models is worthy of additional investigation. A forward chemical genetics approach has been used to show that BTZO-1 derivatives may activate AREs via binding to MIF. Here we show that BTZO-15 directly interacts with MIF and induces ARE-mediated expression of cytoprotective genes, such as GST-Ya and HO-1. This induction of GST Ya mRNA expression by BTZO-15 was decreased in MIF siRNA-transfected H9c2 cells. These results, and those of our previous report, suggest that BTZO-15 activates AREs by binding to MIF. MIF LEE011 reportedly contributes to the symptoms of IBD, and inhibition of MIF could be a potential treatment. However, our results suggest that activation of MIF by BTZO-15 induces ARE activation, leading to the therapeutic effects in IBD models. Further studies are needed to reveal how MIF participates in IBD and how BTZO-15 works in this system. In summary, we demonstrate that BTZO-15 activates AREmediated gene expression and suppresses NO-induced cell death in vitro. In addition, BTZO-15 ameliorates both DSS- and TNBSinduced colitis in rats. Since no ARE activator have been used as therapeutic drugs for IBD, BTZO-15 could be a novel drug for IBD with potent therapeutic activity and a low side effects profile. Our studies further demonstrate that ARE activation can be an attractive and novel approach to IBD therapy. Lower plasma levels and dysfunction of high density lipoprotein are closely associated with metabolic syndrome including cardiovascular diseases, obesity, dyslipidemia and type 2 diabetes mellitus. ABCA1 and ABCG1 are severely decreased in type 2 diabetes mellitus, which inhibit HDL formation and mature due to lower efflux of cholesterol and phospholipid from peripheral tissues. Scavenger receptor type I that mediates HDL uptake is highly expressed under elevated glucose circumstance. Furthermore, other proteins regulating HDL metabolism such as cholesterol ester transfer protein.