玄参抗脑缺血活性分子群及其效应关系研究

Based on previous work, this project, by integrating the scientific methods and technologies of traditional Chinese medicine chemistry, pharmacology, biology and informatics, aimed to have a further research on the blood-cooling active molecular group of Scrophularia ningpoensis Hemsl.. After successfully isolating and identifying the anti-cerebral ischemia effective iridoid glycosides, we used LC-MSn technology to define the mass spectral fragmentation patterns. Afterwards, by screening of the anti-cerebral ischemic activity of iridoid glycosides in vitro as well as the help of DOCK program, the structure-activity relationship of anti-cerebral ischemia effective iridoid glycosides was established. According to fragmentation pattern of iridoid glycosides, the distribution and metabolism in serum and brain tissue were studied in rats after focal cerebral ischemia after oral administration of the active site. And after systematic chemical constituent, fragmentation pattern and composition proportion study of the active site, the active molecular group of the anti-cerebral ischemia were finally constructed and its dose-effect relationship were explored successfully. We firmly believed that this study would help to explain the efficacious material basis for blood-cooling and anti-cerebral ischemia mechanism of Scrophularia ningpoensis Hemsl., moreover, be a valuable reference for the further research and development of traditional Chinese medicine in active molecules group area.

本项目拟在前期工作基础上，整合中药化学、药理学、生物学、信息学等学科方法与技术进行玄参凉血功效抗脑缺血活性分子群研究。完成玄参抗脑缺血活性部位环烯醚萜苷的分离与结构鉴定，应用LC-MSn技术明确环烯醚萜苷质谱裂解规律。通过体外筛选明确具有脑保护活性的环烯醚萜苷，应用DOCK程序分析结构与活性的关系，建立环烯醚萜苷抗脑缺血的构效关系。脑缺血大鼠口服活性部位后，根据环烯醚萜苷的质谱裂解规律进行大鼠血清和脑组织中环烯醚萜苷的分布、代谢研究。研究玄参抗脑缺血活性分子群的成分及组成比例，并根据主要活性成分、活性分子群组成及其代谢规律进行优化组合，利用已建立的大鼠脑缺血模型探索其效应关系及最优组合。探讨玄参抗脑缺血物质基础和活性分子群抗脑缺血的作用机制，为开发具有抗脑缺血作用的现代新型中药奠定基础。

本项目在前期工作基础上，整合中药化学、药理学、生物学、信息学等学科方法与技术对玄参凉血功效抗脑缺血活性分子群进行了研究。完成玄参抗脑缺血活性部位环烯醚萜苷的分离与结构鉴定，应用LC-MSn技术明确环烯醚萜苷质谱裂解规律。通过体外筛选确定了具有脑保护活性的环烯醚萜苷类成分，应用DOCK程序分析结构与活性的关系，建立环烯醚萜苷抗脑缺血的构效关系。脑缺血大鼠口服活性部位后，根据环烯醚萜苷的质谱裂解规律进行大鼠血清和脑组织中环烯醚萜苷的分布、代谢研究。研究玄参抗脑缺血活性分子群的成分及组成比例，并根据主要活性成分、活性分子群组成及其代谢规律进行优化组合，利用已建立的大鼠脑缺血模型探索其效应关系及最优组合。发现了玄参抗脑缺血物质基础和活性分子群抗脑缺血的作用机制，为开发具有抗脑缺血作用的现代新型中药奠定基础。