炎性因子在2型糖尿病的发生和发展中起了重要的作用，可引起胰岛素抵抗(IR)和胰岛β结构与功能障碍。而HMGB1,NF-κB等因子的活化可促进炎性因子的过表达。近年来，炎症通路中NF-κB等关键因子已成为防治T2DM的新靶位。大量研究发现黄酮类和二苯乙烯类天然药物具有良好的抗炎作用。课题组前期从胡芦巴中分离出多个黄酮类和二苯乙烯类化合物，并发现这些化合物能促进IR脂肪细胞的糖摄取能力，且能降低糖尿病小鼠血糖。推测其降糖机制与其抗炎活性相关，可能通过抑制NF-κB的活性、减少炎性因子的表达来改善IR和实现降糖。本项目拟在前期工作的基础上，进一步利用3T3-L1脂肪细胞IR模型，从“HMGB1-NF-κB-IR生物发生”的信号环路出发，辅助以分子生物学方法筛选上述优效化合物，探讨其作用机制，明确作用靶点。然后建立小鼠IR型进行体内验证，阐明胡芦巴改善IR糖代谢的物质基础和作用机制。

Inflammatory factors play an important role in the occurrence and development of type 2 diabetes(T2DM), which can cause insulin resistance (IR) and islet β structural damage and dysfunction. The activation of factors such as HMGB1 and NF-κB can promote the over-expression of inflammatory factors. In recent years, key factors such as NF-κB in the inflammatory pathway have become new targets for the prevention and treatment of T2DM. Studies have shown that flavonoids and polyphenol stilbenes compounds have good anti-inflammatory effects. We have previously found several flavonoids and stilbenes compounds from fenugreek (Trigonella foenum-graecum L.). Which have the activity of promoting the ability of glucose uptake in IR adipocytes and can reduce the blood sugar in diabetic mice. Base on the above, it is speculated that the hypoglycemic mechanism of these compounds is closely related to their anti-inflammatory effect. It may improve IR and achieve hypoglycemic by inhibiting the activity of the NF-κB pathway and then reducing the expression of inflammatory factors. Then, based on the existed research reports and our studies on the fenugreek compounds, we intend to evaluate the bioactivity of the flavonoids and stilbenes components from fenugreek through IR adipocytes. What’s more, the deep mechanisms will be explored through the HMGB1 /NF-κB-IR pathway. The IR model of diabetic mice will be established to assay and verify the effects for the better effective compounds in vivo. We aim to elucidate the mechanism for improving glucose metabolism in IR state and find out the excellent compounds from fenugreek.