缩砂密中新颖二萜类成分及其降糖作用研究

Diabetes mellitus is a kind of metabolic disorders. Its incidence is increasing year by year, and it has become the third disease following cancer and cardiovascular disease. Medicinal herbs play an important role in the prevention and treatment of diabetes. Amomum villosum var. xanthioides belongs to a Dai medicinal plant and its fruits and roots can be used to treat diabetes. Our previous research indicated that novel diterpenes exist in A. villosum var. xanthioides as well as the petroleum ether and the dichloromethane fractions showed significant inhibitory activities against a-glucosidase. Thus, the objective of this project is to discover novel and anti-diabetic diterpenoids by combining bioactivity-guided isolation with modern chromatographic techniques, and to elucidate the material basis of its medicinal efficacy based on models of α-glucosidase inhibitory activity and insulin resistance for type II diabetes. On guidance of pharmacological activities, our research is aimed at finding structurally unique constituents with hypoglycemic effects from the ethnical medicinal plant, which shows great significance for new drugs with independent intellectual property rights.

糖尿病是一种代谢障碍性疾病，患病率逐年上升，已成为继癌症、心脑血管疾病之后的第三大疾病，植物药在糖尿病防治中发挥了重要作用。傣药缩砂密以果实和根入药，可用于糖尿病的治疗。我们研究发现缩砂密的石油醚和二氯甲烷部位存在新颖的二萜成分，并且这两个部位具有显著的α-糖苷酶抑制活性。本项目在前期工作基础上拟采用活性导向和现代色谱分离技术相结合的方法，从缩砂密活性部位中定向分离结构新颖的二萜类成分，并结合α-糖苷酶抑制模型和胰岛素抵抗细胞模型对其降糖作用进行研究，从而阐明缩砂密的药效物质基础。本项目在活性的指导下，从民族植物药中发现结构新颖的活性成分，对开发我国具有自主知识产权的新药具有重要的意义。

本项目以民族药缩砂密的根茎为研究对象，采用各种色谱分离技术，对石油醚和二氯甲烷部位进行化学成分研究，分离鉴定出31个化合物，包括半日花烷型二萜和降二萜18个，倍半萜5个，黄酮和酚类成分5个以及其他类成分3个。发现新化合物5个，其中1个为6/6/5环合的四降半日花烷型二萜新骨架化合物，1个为形成具有罕见五元环状酸酐片段的新颖半日花烷型二萜。对分离得到的萜类成分采用a-糖苷酶抑制模型进行降糖活性研究，并通过酶动力学和分子对接模型探讨其作用机制。同时，为了寻求生物活性多样性，还运用LPS诱导的NO释放模型进行抗炎活性研究。结果表明化合物S-4对a-糖苷酶和NO释放具有显著的抑制活性，为进一步降糖和抗炎药物的研发奠定基础。本项目将复杂天然产物和药理活性及其机制研究相结合，从缩砂密中发现结构新颖的活性单体成分，为缩砂密的进一步开发利用提供依据。