胡芦巴改善Ⅱ型糖尿病的物质基础及作用机制研究获新成果
“青藏高原生态经济植物资源研究与开发”课题组（索有瑞组）最近研究发现，胡芦巴中的黄酮类与二苯乙烯类化合物能够通过提高线粒体功能调节糖脂代谢，进而改善胰岛素抵抗现象。该研究成果“Flavonoid Glycosides from Fenugreek Seeds Regulate Glycolipid Metabolism by Improving Mitochondrial Function in 3T3-L1 Adipocytes in Vitro”（博士研究生栾广祥为第一作者，王洪伦研究员和李刚副教授为通讯作者）和“Polyphenol Stilbenes from Fenugreek (Trigonella foenum-graecum L.) Seeds Improve Insulin Sensitivity and Mitochondrial Function in 3T3-L1 Adipocytes”（博士研究生栾广祥和李刚副教授为第一作者，王洪伦研究员通讯作者。）近期分别发表在 《Journal of agricultural and food chemistry》和 《Oxidative medicine and cellular longevity》杂志上。
该研究发现胡芦巴中的化合物异荭草素（Isoorientin）和丹叶大黄素（Rhaponticin）在10 uM浓度下可以通过升高线粒体膜电势，维持线粒体动态平衡，促进线粒体生物发生，促进线粒体DNA损伤的修复，进而激活AMPK/AKT胰岛素信号通路，促进葡萄糖转运蛋白Glut4从胞浆转运至细胞膜，提高分化成熟的3T3-L1脂肪细胞对的葡萄糖摄取能力。该发现对以胡芦巴为原料开发治疗Ⅱ型糖尿病的药物提供了物质基础，并为以线粒体为靶点治疗Ⅱ型糖尿病的研究提供了理论基础。
图1 异荭草素改善胰岛素抵抗机制图
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.
全文链接：
1 https://pubs.acs.org/doi/abs/10.1021/acs.jafc.8b00179
2 https://www.hindawi.com/journals/omcl/2018/7634362/abs/
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