Studies On Adipogenesis-interfering Effects Of Prenylated Flavonoids From The Genus Morus

This paper consists of two chapters. The first chapter introduces studies on adipogenesis-interfering effects of prenylated flavonoids from the genus Morus. The second chapter is a review about the progress on the adipogenesis-interfering effects of natural products.As an energy store and endocrine organ, adipose tissue plays a significant role in energy balance, insulin action and lipid metabolism of human, and is the center of metabolic regulation. Promotion of3T3L1differentiation can enhance the sensitivity of adipocyte to insulin and promote glucose uptake. It’s a recent research focus on discovering new lead compounds which interfere adipogenesis, reduce insulin resistance and treat type2diabetes from abundant natural resources.The genus Morus is abundant of prenylated flavonoids. In our studies on bioactive constituents of Morus nigra and Morus yunnanensis, some of the compounds were found to show adipogenesis-promoting activity. Thus, deep investigations on the adipogenic effects and mechanism of three representative prenylated flavonoids were carried out.MnPE-11is a sanggennon-type flavanone isolated from Morus nigra. In our studies, we found that MnPE-11significantly promoted adipogenesis with increased glucose uptake in3T3L1cells. MnPE-11dose-dependently increased lipid droplets and lipogenic genes, including CEBPβ、CEBPα、PPARγ and target genes, such as aP2, GLUT4and adiponectin. Then MnPE-11upregulated the activity of PPARγ and the phosphorylation of Akt at the onset of differentiation. Thus, MnPE-11may promote adipogenesis with increased glucose uptake through the Akt pathway and the enhancement of PPARy activity.My-34and my-12are two prenylated flavans isolated from Morus yunanensis. In our studies, my-34were found to significantly promote adipogenesis with increased glucose uptake in3T3L1cells. My-34induced p38phosphorylation at the onset of differentiation. The p38inhibitor could negatively affect my-34-promoted adipogenesis and glucose uptake. My-34increased the sequential expression of CEBPβ、CEBPα and PPARγ, which were reversed by the p38inhibitor. Moreover, my-34inhibited TNF-a mRNA expression after adipocyte differentiation. Hence, my-34can promote adipogenesis with increased expression of CEBPβ、 CEBPα and PPARy through the p38pathway. My-12could also promote adipogenesis with increased glucose uptake in3T3L1cells. My-12dose-dependently increased lipid droplets and lipogenic genes, including CEBPβ、CEBPα、PPARy and target genes, such as aP2, GLUT4and adiponectin. My-12and my-34have similar structures, but my-12could not increase p38phosphorylation at the onset of differentiation.In conclusion, the three prenylated flavonoids from the genus Morus can promote adipogensis, increase insulin sensitivity and facilitate glucose uptake, which is significant to discover drug candidate for the treatment of type2diabetes mellitus.