人参叶调控菌—炎功能轴稳态的抗2型糖尿病物质基础及作用机制研究

项目名称： 人参叶调控菌—炎功能轴稳态的抗2型糖尿病物质基础及作用机制研究

项目编号： No.81503191

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 毛茜

作者单位： 南京中医药大学

项目金额： 18万元

中文摘要： 人参叶资源丰富，我国药典和古代医学论著记载可用于“生津，止消渴”。现代研究表明人参叶有确切的降糖活性。但药效物质基础和作用机制不明已然成为制约人参叶药用价值深度开发的瓶颈问题。肠道菌群介导的NLRP3炎症小体激活是2型糖尿病重要致病原因之一。前期研究发现：人参叶含有侧链异构型达玛烷皂苷等特征性成分；并能有效降低血糖、调节肠道菌稳态和炎症因子。为此，我们提出如下科学假说：人参叶通过调控“菌”(肠道菌)—“炎”(NLRP3炎症小体)轴稳态：即调节肠道菌稳态，减少致病菌数量、脂多糖和ROS水平，从而抑制NLPR3炎症小体激活，发挥降糖作用。拟运用C57BL/KsJ db/db自发性糖尿病小鼠为模型； UPLC-QTOF-MS/MS，16S rRNA RT PCR、ELISA等多学科交叉技术，揭示人参叶调控2型糖尿病的药效物质基础和作用机制，为其降糖价值深度开发和资源充分利用提供科学依据。

中文关键词： 人参叶；2型糖尿病；NLRP3炎症小体；物质基础；作用机制

英文摘要： Leaves of Panax ginseng (LPG), with abundant natural material resource, is usually neglected for its role of non-traditional medical part. Description of LPG’s medicinal effects found in the ancient Chinese materia medica contained several references to its ability to “quench thirst”. LPG has been documented in Chinese pharmacopoeia (2010 edition) for its “stimulate saliva” and “quench thirst” effects. In our previous study, it has been found that the chemical profile of LPG is totally different from that of roots, which implies the pharmacological activity may be different. These years, scientists found extract of LPG could decrease baseline blood glucose and reduce hyperglycemia in ob/ob mice or diabetic rat caused by STZ. And the leaves extract exhibited significantly more potent anti-diabetic effects than that from the root. However, unclear material base and anti-diabetes mechanism limited exploration of the potential hypoglycemic value of LPG. Recent years, a number of reports indicated that activation of NLRP3 inflammasome involved by gut microbiota plays a central role on the development of type 2 diabetes. Increasing level of gut microbiota-derived lipopolysaccharide (LPS) and ROS induced by hyperglycemia are major factors involved in the onset and progression of inflammation and diabetes. Previously, we found that extract of LPG reduced hyperglycemia and body weight in diabetic rat caused by high-fat diet and STZ. Based on our previous results and the characteristics of gut microbiota and NLRP3 inflammasome, we raise the hypothesis that LPG could regulated the homeostasis of gut microbiota-NLRP3 inflammasome axis, including reducing the level of LPS and ROS, so as to inhibit the activation of NLRP3 and consequently control the development of type 2 diabetes. In this proposal, the material base will be investigated by UPLC-QTOFMS/MS and LC-TQ-MS/MS. The anti-diabetic mechanism will be explored by 16S rRNA PCR、ELISA and other pharmacological technique. As a consequence, the bioactive components of LPG and anti-diabetic mechanism will be revealed, which may promote exploration of anti-diabetic value and contribute to the realization of a resource-saving and environment-friendly recycling resource development.

英文关键词： Leaves of Panax ginseng;Type 2 Diabetes;NLRP3 inflammasome;Material base;Mechanism