大蓟黄酮类化合物挖掘、改造与抗糖尿病研究

In the preliminary study by this project team, series of Cirsium japonicum flavonoids were isolated and purified. It was confirmed that Cirsium japonicum flavonoids have anti-diabetic activity, but their anti-diabetic activity significantly differs according to the structural difference. In this study,the Cirsium japonicum plant will be dealt with under extreme environmental conditions, and then the flavonoids will be extracted with modern separation techniques. Based on the chemical structures of the existing Cirsium japonicum flavonoids with bioactivity, Cirsium japonicum flavonoid derivatives will be prepared through organic synthesis. Using the diabetic rats and insulin-targeted cells as research system, the anti-diabetic activity of the Cirsium japonicum flavonoids and their derivatives will be investigaed at animal, cellular and molecular levels.In this project, to investigate the anti-diabetic activity of Cirsium japonicum flavonoids and their derivatives with different chemical structure and their regulating insulin signaling role is taken as the starting point,aimed at studying the structure-activity relationship of Cirsium japonicum flavonoids regarding their anti-dabetic activity. This research will provide the theoretical basis for mining and acquiring cirsium japonicum flavonoids with strong anti-diabetic activity, and guide the directed transformation of existing bioactive flavonoids.

本项目组前期研究分离纯化得到系列大蓟黄酮类化合物，并证实大蓟黄酮类化合物具有抗糖尿病活性，但其抗糖尿病活性随结构差异而明显不同。本研究拟采用极端环境条件处理各种大蓟，利用现代分离技术提取大蓟黄酮类新化合物，同时以已有大蓟黄酮类活性化合物的结构为基础，采用有机合成法制备大蓟黄酮类衍生物。以糖尿病大鼠和胰岛素靶细胞为研究体系，从动物、细胞、分子水平研究大蓟黄酮类化合物及其衍生物抗糖尿病活性。本研究以不同结构的大蓟黄酮类化合物及其衍生物的抗糖尿病活性和对胰岛素信号作用的调控为切入点，旨在研究大蓟黄酮类化合物在抗糖尿病活性方面的构效关系，为挖掘、获取高效抗糖尿病活性的大蓟黄酮类化合物奠定理论基础，指导现有黄酮类活性化合物的定向改造。

项目研究组在前期研究中分离纯化得到系列大蓟黄酮类化合物，并证实大蓟黄酮类化合物具有抗糖尿病活性，但其抗糖尿病活性随结构差异而明显不同。因此，本项目采用极端环境条件处理l了大蓟，利用现代分离技术提取了大蓟黄酮，分析了大蓟黄酮类化合物的组成与丰度异同，以期得到新化合物。同时以已有大蓟黄酮类活性化合物的结构为基础，采用有机合成法制备了大蓟黄酮类衍生物；以糖尿病大鼠和胰岛素靶细胞为研究体系，在动物、细胞、分子水平研究了大蓟黄酮类化合物及其衍生物抗糖尿病活性和对胰岛素信号作用的调控，探讨了大蓟黄酮类化合物在抗糖尿病活性方面的构效关系，为挖掘、获取高效抗糖尿病活性的大蓟黄酮类化合物奠定了一定的理论基础，将有助于指导现有黄酮类活性化合物的定向改造。