内蒙古两种青兰属植物活化AMPK信号通路二萜化合物的发现及作用机理研究

With the improvement of living standards, hyperlipidemia showed an increasing trend. Furthermore, hyperlipidemia is one of the most important risk factors in the development and progression of metabolic diseases, such as atherosclerosis and type II diabetes, which have considerable effects on the quality of life and survival of patients. Due to its roles in fuel regulation, the AMPK pathway is regarded as a potential therapeutic target for hyperlipidemia. Therefore, identification of novel activators of AMPK pathway represents an attractive starting point for developing anti-hyperlipidemia drugs. In our previous study, the total diterpenoids of Dracocephalum moldavica L. have been identified as the activators of AMPK pathway. The aim of this work was to isolate and identify the exact chemical structures of more potent natural diterpenoid activators of AMPK pathway from two dracocephalum species (Dracocephalum moldavica L. and Dracocephalum rupestre Hance) in Innner Mongolia, which are rich in diterpenoids. Once we identify diterpenoids that are activators of AMPK pathway, we will investigate their mechanism of action in cellular assays. This work not only provides excellent opportunities to identify novel anti-hyperlipidemia lead compounds, but also provides some new information which may be helpful for understanding the major mechanism for AMPK regulation. Moreover, knowledge of two dracocephalum species in terms of potency is useful in their rational exploitation and utilization.

随着人们生活水平的不断改善，高脂血症等代谢性疾病的发病率急剧升高，成为严重影响人们生活质量及预期寿命的重要原因。AMPK信号通路是一个重要的高脂血症等代谢性疾病的药物作用靶标，故发现新型AMPK信号通路激动剂对于合理开发应用抗高脂血症等代谢性疾病药物具有重要意义。本项目拟结合内蒙古药用植物资源及AMPK信号通路对脂代谢具有重要调节作用的理论，在研究香青兰总二萜能够活化AMPK信号通路的基础上，从含有丰富二萜物质的内蒙古地区两种青兰属（香青兰和岩青兰）植物中识别、分离二萜化合物，对化合物进行结构鉴定，并进一步从细胞水平探讨化合物的作用机制。研究结果不仅有望发现新型具有活化AMPK信号通路的活性化合物，为治疗高脂血症等代谢性疾病的药物研究提供先导结构，而且可为揭示AMPK信号通路的调控机理、进一步合理开发利用这两种青兰属植物奠定基础。