ABSTRACT 1: Fenugreek is a well known annual herb widely used in both medicine and food. Four flavonoid glycosides have been separated from fenugreek seeds in our previous study. In this study, the effects of the four flavonoid glycosides on regulating glycolipid metabolism and improving mitochondrial function were investigated. Isoorientin showed a very significant activity among these flavonoid glycosides. First, isoorientin decreased the accumulation of lipid droplets in 3T3-L1 preadipocytes by reducing the expression of adipokines including PPARγ, C/EBPα, and FAS. Second, isoorientin restored insulin-stimulated glucose uptake in dexamethasone-induced insulin-resistant 3T3-L1 adipocytes by reactivating Akt and AMPK. Finally, isoorientin improved mitochondrial dysfunction induced by dexamethasone in 3T3-L1 adipocytes. Isoorientin also reversed dexamethasoneinduced decrease in mitochondrial membrane potential (MMP) and intracellular ATP production, reduced accumulation of intracellular reactive oxygen species (ROS), and protected mitochondrial DNA (mtDNA) from oxidative damage. At the same time, mitochondrial biogenesis is promoted. Therefore, isoorientin may be an attractive candidate as a glucose-lowering and insulin-resistance-improving agent for the treatment of diabetes.
ABSTRACT 2: Fenugreek (Trigonella foenum-graecum L.) is a well-known annual plant that is widely distributed worldwide and has possessed obvious hypoglycemic and hypercholesterolemia characteristics. In our previous study, three polyphenol stilbenes were separated from fenugreek seeds. Here, we investigated the effect of polyphenol stilbenes on adipogenesis and insulin resistance in 3T3-L1 adipocytes. Oil Red O staining and triglyceride assays showed that polyphenol stilbenes differently reduced lipid accumulation by suppressing the expression of adipocyte-specific proteins. In addition, polyphenol stilbenes improved the uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) by promoting the phosphorylation of protein kinase B (AKT) and AMP-activated protein kinase (AMPK). In present studies, it was found that polyphenol stilbenes had the ability to scavenge reactive oxygen species (ROS). Results from adenosine triphosphate (ATP) production and mitochondrial membrane potentials suggested that mitochondria play a critical role in insulin resistance and related signaling activation, such as AKT and AMPK. Rhaponticin, one of the stilbenes from fenugreek, had the strongest activity among the three compounds in vitro. Future studies will focus on mitochondrial biogenesis and function.