香花羊耳蒜降脂作用及其活性物质研究

Hyperlipidemia(HLP) is a disease of high occurrence, easily causing atherosclerosis, which is a serious threat to the happening of coronary heart disease, high blood pressure, as well as cerebrovascular diseases and diabetes, so, HLP is one of the top ten hidder death to the human health in modern society. And, most synthetic drugs used to treat HLP have many side effects, up to now there is no good way to treat with HLP. So, looking for natural, safe, effective lipid-lowering drugs and studying their treating mechanism to HLP, are important topics to the vast of medical workers. .Liparis odorata is a plant of orchid family, which is used for the treatment of hyperlipidemia in the folk of Jiangxi province, and showing good function, but less research has been done all of world, so its hypolipemic effect together with bioactive constituents are still unknown. A systematical research on the chemical constituents from Liparis odorata has been done in our group, and six compounds, including two new alkaloids were identified for the first time, and both two alkaloids showed significant lipid-lowering activity in preliminary pharmacological experimental. .So, in this project, basing on modern chemical method and pharmacology experimental, study on hypolipemic effect of the plant as well as the isolation and identification of bioactive compounds shall be carried on, which is good for the experimental basis to natural drugs.Also deeply study on lipid-lowering mechanism of active components shall be done, for the purpose of providing theoretical foundation to declear the occurence and prevention of hyperlipemia. Study on the quantitative structure-bioactivity relationship of active constituents shall be focused on simultaneously, which develops the new ways for the directed synthesis and application of active constituents.

高脂血症发病率高，易引发动脉粥样硬化，是造成冠心病、高血压、脑血管疾病及糖尿病的重要原因，被称为现代社会严重威胁人类健康的十大隐性死亡之一，临床治疗西药副作用大，迄今无特效疗法。所以，寻找天然安全有效降脂药物并探讨高脂血症形成原因，是广大医药工作者关注的重要课题。香花羊耳蒜是兰科植物，江西民间用于治疗高脂血症，疗效确切，但国内外对其研究较少，至今其降脂作用机制及活性物质不清。本课题组对香花羊耳蒜进行了系统化学成分研究，目前已分离鉴定6个化合物，其中2个新生物碱类成分经初步药理实验研究显示确切降脂活性。因此，本项目拟系统研究香花羊耳蒜的降脂作用，采用现代化学方法及药理实验，分离鉴定其中降脂活性物质，为开发具有确切疗效的天然药物提供实验依据；深入研究降脂活性物质的作用机制，为揭示高脂血症的形成原因及防治高脂血症奠定理论基础；研究活性成分的定量构效关系，为活性成分的定向合成和开发应用开辟新途径。

首次在国内对江西省地产植物香花羊耳蒜进行了系统的化学成分和生物活性研究，为香花羊耳蒜的开发利用创造了良好条件，为降脂新药研制奠定了理论基础，有利于促进江西省经济建设和人类健康事业发展。本项目在以下方面进行了重点研究并取得重要成果：1、首次从香花羊耳蒜中分离鉴定了41个化合物，其中18个新化合物，分别命名为liparisalkaloid A（1）、liparisalkaloid B（2）、liparisalkaloid C（3）、liparis glycoside A（4）、liparisglycoside B（5）、liparisglycoside C（6）、liparis glycoside D（7）、liparisglycoside E（8）、liparisglycoside F（9）、liparis glycoside G（10）、liparisglycoside H（11）、liparisglycoside I（12）、liparis glycoside J（13）、liparisglycoside K（14）、liparisglycoside L（15）、liparisglycoside M（16）、liparisglycoside N（17）、liparisglycoside O（18）等。23个已知化合物均是首次从羊耳蒜属植物得到。2、首次系统研究了香花羊耳蒜的化学部位及单体化合物的体外降脂及抗炎等生物活性，结果表明：95%乙醇提取液、乙酸乙酯部位和正丁醇部位均显示较强体外抑制细胞脂质活性，3个新生物碱均显示体外抑制细胞脂质作用，其中liparisalkaloid A和liparisalkaloid B的抑制作用显著。香花羊耳蒜醇提物呈明显体外抗炎作用，具有显著性差异，单体化合物Anodendrosin A的水解物I-3和liparisglycoside C显示抑制NO分泌作用，呈现抗炎活性。香花羊耳蒜生物碱属吡咯里西啶类生物碱，降脂作用构效关系研究表明生物碱结构中的N→O配位键降低N原子的电子云密度，降低生物碱毒性，有利于降脂、抗肿瘤等生物活性。3、具体成果：公开在SCI收录杂志发表学术论文4篇，详细报道了香花羊耳蒜的研究成果；申请专利1项；培养硕士研究生3名。