糖尿病是危害人类健康的重大疾病，抑制肝脏过度糖异生，减少内源性葡萄糖的生成，是治疗2型糖尿病的重要途径之一。卡山烷二萜是一类结构独特的天然产物，主要存在于豆科云实属植物中。申请人前期研究发现一系列卡山二萜类成分，并发现数个活性显著的抑制糖异生作用化合物。通过体内活性评价，卡山烷二萜phanginin A长期给药后可显著降低2型糖尿病ob/ob小鼠的空腹和随机血糖，是一个潜在抗糖尿病苗头化合物。基于此，本项目拟以富含卡山烷二萜的云实属植物为研究对象，通过植物化学手段定向获取卡山烷二萜类成分，通过体外抗糖异生活性筛选发现活性成分。对活性成分开展结构修饰与抗糖尿病活性评价，阐明构效关系，发现药物先导化合物，为云实属植物资源开发利用奠定基础。

Diabetes mellitus is a serious diseases threatening human health. Inhibition of gluconeogenesis and decrease of endogenous glucose production is one of the key ways for the treatment of type 2 diabetes mellitus. Cassane diterpenoids are a class of natural products with unique structures. A series of cassane diterpenoids have been found in our previous study, some of which exhibited potent gluconeogenesis inhibitory activity. Phanginin A, a potential anti-diabetic compound, could significantly reduce the random and fasting blood glucose in type 2 diabetic ob/ob mice after long-term administration. Therefore, Caesalpinia species, which are rich in cassane diterpenoids, will be selected as this research object. The characteristic chemical constituent will be explored by phytochemical methods, and their gluconeogenesis inhibitory activities will be evaluated by in vitro screening. Then, structural modification, anti-diabetic activity evaluation in vivo and in vitro, and structure-activity relationship of the bioactive constituents will be carried out to find new natural lead compound. This project will also provide the foundation for resource utilization of Caesalpinia species.