菊苣子作用于糖尿病多靶点活性成分及其整合作用机制研究

Type 2 diabetes mellitus (T2DM) is a kind of glucose and lipid metabolic disorder disease caused by multi-factors, which present the fast growth trend in worldwide. It’s difficult to obtain ideal treatment based on the "one target – one compound - one disease" mode. The multi-target based T2DM treatment has been concerned gradually. Multiple active constituents of TCMs play a role in multi-target and multi-pathway and show the integration effects, which coinide the therapeutic strategy in complex diseases. The results of previous research showed that Cichorium glandulosum seeds could ameliorate diabetic state. But the targets and the chemical compositions were still unclear. This project aims to clarify the active components based on PPARα/β/γ、PTP1B、α-glucosidase multi-targets screening. Study the effects of these compounds on TNF-α stimulated insulin resistance in 3T3-L1 adipocyte, the insulin signaling pathway related protein kinase phosphorylation reaction. The effects on insulin secretion in INS-1E β- cells and the expression of genes involved in β-cells survival and function would be studied. At the same time, the targets and mechanism of integration effects would be elucidated. The study would provide the scientific basis for Cichorium glandulosum seeds in T2DM treatment, and laid the foundation for the development of the related new medicine.

Ⅱ型糖尿病（T2DM）是多因素导致的一种糖脂代谢紊乱综合征，近年来发病率一直呈快速增长趋势，而现行的“单一靶点-单一化合物-治疗一种疾病”模式已难获得理想的治疗效果，故基于多靶点治疗糖尿病的研究目前备受关注。而传统药物通常是多种成分通过作用其多靶点、发挥多途径的整合作用来实现其治疗目的，这和现代医学对多因素导致疾病的多靶点治疗策略非常契合。我们前期研究证明菊苣子具有糖尿病的治疗效果，但其有效物质基础及作用靶点不明。本项目旨在基于PPARα/β/γ、PTP1B、α-糖苷酶等多靶点的筛选，明确菊苣子治疗T2DM的物质基础，通过研究其对TNF-α诱导的3T3-L1脂肪细胞形成的胰岛素抵抗、胰岛素信号转导通路蛋白激酶磷酸化过程、以及INS-1E细胞胰岛素释放及相关基因表达的作用和影响，阐明其活性成分的作用靶点和整合作用机制，为菊苣子治疗T2DM提供科学依据，进而为相关新药的研发奠定基础。