苦瓜葫芦烷三萜化合物库的构建、减肥活性及作用机制研究

Obesity, representing as lipid excessive accumulation and chronic inflammation, is a public health killer.Obesity is also involved with hypertension, type II diabetes, coronary heart disease, and paralytic stroke, etc. At present, some diet drugs are very popular, but also show certain side effects. Finding natural diet drugs from vegetables and fruits is becoming more and more promising approach. The fruit of Momordica charantia L. is very popular in southeast and south Asian counties, and it also has the function to treat diseases, such as diabetes and obesity. In previous studies,we isolated and identified 103 cucurbitane compounds from M. charantia, and there were 52 new ones, nearly up to one-second new compounds obtained from this species around the World. And the studies on adipogensis showed that the compound, BM-G, isolated from previously from M. charaantia, displayed strong activities on both the models of insulin-induced 3T3-L1 adipocytes and Caenorhabditis elegans. Carried out this project, both ammount and number of cucurbitane compounds from M. charantia will be enlarged. At the same time, the laten valuable usage and prospect will be evaluated by enriching the bioactive compounds to be tested on animals.By doing so, we hope to find new lead antihyperlipidemics compounds, or to establish the academic base on exploiting medicine to treat obesity.

肥胖是一种严重危害人类健康的慢性炎性疾病，表现为脂肪过度沉积与低度炎症反应。肥胖与高血压、II型糖尿病、冠心病和中风等多种疾病的发生关系密切。时下流行的减肥药物往往伴随有较大的毒副作用。从大自然，特别是蔬菜水果中找寻高效低毒的天然减肥药物，是具有无限前景的途径。苦瓜果实是比较受东南亚及南亚国家喜爱的蔬菜，同时伴有降血糖、血脂的功能。在前期研究中，申请者所在的课题组已经从数个苦瓜样品中分离鉴定103个三萜葫芦烷型化合物。其中，新化合物52个，几乎占该植物中发现的新化合物的二分之一。抑制脂肪沉积活性研究发现，化合物BM-G在3T3-L1前脂肪细胞和秀丽线虫两个模型中，表现了极好的活性，分别强于阳性对照。 本项目将在此基础上，扩大化合物活性研究数量，并富集活性化合物进行抗脂肪沉积动物实体试验，对其潜在应用价值和前景作出评估。以期从苦瓜中发现新型降血脂先导化合物，或为开发出治疗药物奠定理论基础。

分别对产自云南、广东、安徽、新疆等省的7个苦瓜样品进行了化学成分提取分离、纯化、结构鉴定，得到不重复的葫芦烷型三萜化合物156个，新化合物47个。另外，还得到了两个结构比较新颖的化合物，其新奇之处在于化合物的支链部分通过碳健与另一个单糖相连而成；由于分离得到了大量的葫芦烷三萜化合物，易于使我们建立了苦瓜单体化合物库及各单体化合物的指纹图谱。目前，收集并保存苦瓜三萜化合物145个，20 mg数量级以上的化合物40个。进一步对分离得到的化合物作抑制脂肪沉积活性研究，发现化合物，3,7,25-Trihydroxycucurbita-5,(23E)-diene-19-al，在3T3-L1前脂肪细胞和秀丽线虫两个模型中，表现了极好的活性。对部分化合物做降血糖活性实验，对部分化合物做降血糖活性实验，有12个苦瓜单体化合物在10uM浓度下显示有潜在的胰岛素增敏活性。通过本项目的实施，奠定了苦瓜可作为减肥食品的理论基础。