Regulation of mammalian gene expression by bioactive compounds from Cinnamon bark

Bioactive components in plant products have been used for the prevention and treatment of various diseases since ancient history. One of the major classes of bioactive compounds is plant polyphenols, which are found in seeds, fruits, leaves and bark. Cinnamon has been used to treat people with type 2 diabetes based on the insulin-like activity of cinnamon polyphenol extract (CPE); however, molecular characterization of the effect of CPE is limited. This study evaluated the regulation of mammalian gene expression by CPE to test the hypothesis that CPE has insulin-like and insulin-independent effects. Quantitative real-time PCR was used to investigate CPE effects on the expression of more than 50 genes coding for the glucose transporter (GLUT) family, insulin-signaling components, adipokines, the anti-inflammatory tristetraprolin (TTP) family, pro-inflammatory cytokines and related gene targets in mouse 3T3-L1 adipocytes. CPE increased GLUT1 and TTP mRNA levels up to 7 and 10 fold, respectively. The levels of vascular endothelial growth factor (VEGF) mRNA, a putative target of TTP, were decreased 40-50% by CPE treatment. CPE decreased the expression of most genes encoding insulin signaling pathway proteins. The insulin-like effects of CPE include rapid induction of TTP mRNA, and the reduction of mRNA for VEGF and genes in the insulin-signaling pathway. The insulin-independent effects of CPE include sustained increases in GLUT1 and TTP expression. These results indicate that CPE regulates multiple gene expression targets in adipocytes and suggests that the health benefits of cinnamon are due to both its insulin-like and insulin-independent effects.