头花蓼降血糖活性物质基础的研究

To find out the new type anti-diabetic drug is constantly important in the field of new drug development, and the kind of new drugs from the inhibitor of dipetidyl peptidase (DPP-4) is one hot spot at present. In our previous study, we found that the Poygonum capitatum has the best activity of decreasing sugar in the screening experiment of 120 species clearing heat Chinese herbal drugs. It was showed not only having the good activity of inhibition α-glucosidase and DPP-4 in vitro, but also having the good activity of decreasing mice' blood sugar in vivo. In this study, we will use the α-glucosidase and DPP-4 inhibition models to screen the activity constituents, and column chromatography of silica gel, Sephadex LH-20, ODS and pre-HPLC will be used to isolate the activity constituents from the plant of Poygonum capitatum. Their structures and configurations will be elucidated by chemical methods and spectral analysis, such as MS、1H-NMR、13C-NMR、DEPT、COSY、HSQC、HMBC、ROSEY methods and single crystal X-ray diffraction. The effect position and the chief active compounds from Poygonum capitatum will be validated by the spontaneous diabetes high blood serm insulin db/db mice' model. The results of this study will be furnished fundamental data for scientific research and product development of the Chinese herbal drug of Poygonum capitatum.

新型抗糖尿病药物一直是新药研发的重点领域，其中的二肽基肽酶（DPP-4）抑制剂是热点之一。我们前期对常见120种清热类中药进行降血糖活性筛选过程中，发现了中药头花蓼（Polygonum capitatum）具有显著的降糖活性，不仅在体外对α-葡萄糖苷酶和DPP-4具有较强的抑制作用，而且在体内可明显降低小鼠餐后血糖水平。本项目将在前期的研究基础上，应用体外α-葡萄糖苷酶和DPP-4模型，采用多种色谱分离技术对活性成分进行跟踪筛选、分离纯化，综合应用波谱方法和化学方法鉴定活性化合物结构，并以自发性糖尿病高血清胰岛素db/db小鼠模型确证有效部位或主要高活性成分药效，以期阐明头花蓼中具有降糖作用的物质基础，为头花蓼进一步新药开发提供科学依据。

前期对常见120种清热类中药进行降血糖活性筛选过程中，发现了头花蓼（Polygonum capitatum）具有显著的降糖活性，不仅在体外对α-葡萄糖苷酶和DPP-4具有较强的抑制作用，而且在体内可明显降低小鼠餐后血糖水平。本项目在前期的研究基础上，对头花蓼有效部位的化学成分进行了较深入的研究，分离并鉴定了63个化合物，并以高脂高糖/STZ诱导糖尿病大鼠模型确证有效部位药效，同时进行了高活性成分β-1,6-六羟基联苯二甲酰基-2,3,4-三没食子酸基-D-葡萄糖（Davidiin）对链脲菌素糖尿病大鼠的糖、脂代谢及肾脏病变的影响实验，确证了Davidiin能够降低餐后血糖水平，改善受损葡萄糖耐量，阻滞血红蛋白蛋白的糖基化、降低胰岛素抵抗、促进胰岛细胞再生，缓解氧化应激压力，还能够改善糖脂代谢。本研究成果为头花蓼进一步新药开发提供了科学依据。