黄花败酱改善3T3-L1脂肪细胞胰岛素抵抗的活性成分及作用机制研究

糖尿病因其高发病率和高死亡率严重影响人们的生活健康，其发病机制复杂，目前普遍认为是胰岛素抵抗，而炎症可能是引起胰岛素抵抗的重要因素。以改善炎症与胰岛素抵抗为方向，从天然产物中寻找抗糖尿病药物，成为研究的热点。前期研究发现黄花败酱提取物具有抗胰岛素抵抗活性；目前从乙酸乙酯部位中发现5个化合物可显著促进葡萄糖摄取，其中patrinoside (10) 和新化合物13可激活PI3K/Akt信号通路调控葡萄糖摄取。但活性更好正丁醇部位是否存在活性更好的化合物及构效关系、作用机制等值得深入研究。因此，本项目拟在前期工作基础上，继续开展活性部位物质基础研究，以影响胰岛素抵抗葡萄糖摄取和炎症反应为方向，寻找活性更强的分子，探讨初步构效关系，并阐明强活性分子的作用机制。本项目的实施有望获得抗糖尿病药物的先导化合物，同时阐明黄花败酱改善胰岛素抵抗的活性分子及作用机制，进而为开发利用黄花败酱植物提供科学依据。

Diabetes mellitus seriously affects people's life and health because of its high morbidity and mortality. Its pathogenesis is complexed and now it is generally believed to be insulin resistance, which may relate to inflammatory response. Thus, it has been a popular research direction to look for antidiabetic drugs from natural products under the guidance of improving inflammation and insulin resistance. Previous studies have found that five compounds from the EtOAc extract of Patrinia scabiosaefolia could significantly promote glucose uptake. Among theme, patrinoside (10) and the new compoud 13 could activate PI3K and Akt signaling to mediate glucose uptake. However, their effects on inflammation, other compounds with better activities in n-butanol extract, structure-activity relationship and their mechanisms are worthy to make further studies. Hence, in this project, the substantial basis from n-butanol extract will be identified systematically to find compounds with better activity. Their structure-activity relationship and mechanisms will be discussed under the guidance of improving inflammation and insulin resistance in 3T3-L1 adipocytes. The implementation of this project may obtain anti-diabetic lead compounds, and illuminate the active ingredients on improving insulin resistance of P. scabiosaefolia and their mechanisms, and then provide scientific basis for the development and effective use of P. scabiosaefolia.