高脂血症可诱发动脉粥样硬化、高血压、糖尿病、冠心病或其它心脑血管疾病，是一类常见多发症。现有的靶向降脂药物均为单一适应症的药物，疗效有限且副作用较大。故"单靶点、双靶向"的药物已成为降血脂药物研发的一个重要方向。脂质代谢过程受到多种蛋白的正负调控，其中，SREBP既能调控脂肪酸的合成又能调节胆固醇的合成，是脂质代谢的关键调节因子。在前期工作中，我们发现大叶冬青叶总皂苷部位具有显著的降血脂、降血糖、调节胰岛素抵抗和减轻肝脏细胞脂肪化的作用，并从中分离鉴定了一系列新型的苦丁内酯型三萜皂苷。活性结果显示，该类化合物可显著抑制3T3-L1细胞向脂肪细胞的分化，初步的机制研究提示该类成分作用的作用靶点可能为SREBP。本项目拟在前期工作基础上，进一步分离和富集大叶冬青叶中的苦丁内酯型三萜皂苷类化合物，并评价和研究其抑制调节脂质代谢的生物活性及作用机制，为研究和开发有效无毒的降血脂药物提供科学依据。

Hyperlipidemia is closely related to metabolic diseases, such as atherosclerosis, hypertension and type II diabetes, which are becoming worldwide problems. Sterol regulatory element-binding protein (SREBP) is major transcription factors activating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. We previously discovered that total triterpenoid saponins of Ilex latifoloside Thunb descreased the lipid and glucose contents in serum and tissues, and improved insulin resistance in the high-fat diet-fed C57BL/6 mice. Furthermore, we demonstrated the inhibitory effect of several kudinoside，isolated from Ilex latifoloside Thunb, on 3T3-L1adipocyte differentiation induced by insulin through suppression of SREBP activation. With the support of this fund, we will further isolate and identify more new compounds, and investigate their functions on lipid metabolism and the inhibitory activity of SREBP.The present study will provide more insights for developing the effective safety new drug for the treatment of hyperlipidemia.