Inhibitory Effects of Indirubin-3′-oxime Derivatives on Lipid Accumulation in 3T3-L1 Cells

Abstract

Obesity elevates the risk of cardiovascular disease and has been strongly associated with increases in the incidence of many metabolic diseases. Therefore, prevention of obesity leads to the prevention of metabolic diseases. In light of this, substances that exert anti-obesity effects are crucial for the prevention of obesity. Indirubin, a 3,2′ bisindole isomer of indigo, is the active component of the traditional Chinese medicine used for the treatment of chronic myelocytic leukemia. In particular, indirubin-3′-oxime (1) was shown to inhibit the differentiation of adipocytes. In this study, we investigated the inhibitory effects of nine indirubin-3′-oxime derivatives against lipid accumulation during differentiation in 3T3-L1 cells. Among the compounds tested, 5-methoxyindirubin-3′-oxime (2) and 6-bromoindirubin-3′-oxime (7) at 5 µM exhibited significantly stronger inhibitory activity than indirubin-3′-oxime (1). Furthermore, 5-methoxyindirubin-3′-oxime (2) and 6-bromoindirubin-3′-oxime (7) markedly suppressed the expression of CCAAT/enhancer-binding protein α, peroxisome proliferator activator γ2, and adipocyte protein 2, both of which are key adipogenic regulators at the intermediate stage of adipocyte differentiation. Our results demonstrate that 5-methoxyindirubin-3′-oxime (2) and 6-bromoindirubin-3′-oxime (7) significantly downregulated lipid accumulation during differentiation of 3T3-L1 cells, suggesting their potential as novel therapeutic drugs against the development of obesity.