基于代谢组学技术的香附-川芎药对配伍规律和抗抑郁药效活性成分研究

项目名称： 基于代谢组学技术的香附-川芎药对配伍规律和抗抑郁药效活性成分研究

项目编号： No.81503230

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： 贾红梅

作者单位： 中国医学科学院药用植物研究所

项目金额： 18万元

中文摘要： 药对是中医临床遣药组方常用的配伍形式，组成简单却隐含了方剂的配伍特征，作为单味中药与若干方剂之间的桥梁，以相对简单的药对为切入点，研究其组成规律，是揭示中药方剂配伍规律和物质基础的捷径。香附-川芎药对见于越鞠丸、柴胡疏肝散、小温中丸、四白丹和芎附饮等方剂，具有行气疏肝功效，临床上主治气郁、肝郁所致的胸胁疼痛等症。本课题组前期研究发现香附和川芎均具有抗抑郁作用，且二者配伍后作用显著增强。因此，本课题拟以代谢组学和化学指纹图谱相结合，研究香附-川芎药对配伍前后化学成分的改变，以及对慢性应激导致大鼠机体代谢紊乱调控作用的影响，利用数据挖掘技术，进行化学成分-生物标志物-药效相关性分析，结合细胞水平和分子水平验证，阐明香附-川芎药对配伍特征，揭示其抗抑郁药效成分群及其代谢调控的通路和靶点。该研究不仅可为含香附-川芎药对的方剂研究提供科学依据，而且可为药对配伍和药效物质基础研究提供新的思路及方法。

中文关键词： 代谢组学；药效成分群；配伍规律；相关性分析；抗抑郁

英文摘要： Chinese medicine pairs (CMP) are specific compatibility with traditional Chinese medicine (TCM) theory as principle，which was formed on basis of effect and treatment theory of TCM. So，study on the compatibility effects of CMP can provide scientific basis for the clinical applications of CMP and creation of TCM new drugs. Xiangfu-Chuanxiong herb pair (XC) is a traditional chinese medicine herb pair with confirmed effect in treatment of qi stagnation caused depression and pain in clinic. Our previously work showed that the antidepressive action of XC was evaluated due to the synergy effects of Xiangfu and Chuanxiong. Therefore, experiments to explore the chemical compositions and compatible regularity of XC herb pair designed to make a thorough research based on metabonomics, combining NMR, UPLC-MS/MS, natural products chemistry and pharmacodynamics, et al. In this study, NMR and UPLC-MS-based metabonomics study will be applied to explore the development of the disease of chronic unpredictable stimulation model (CUMS) and the intervention process of Xiangfu-Chuanxiong herb pair through compared the metabolic profiles of rats’ blood and urine. Combined with the multivariate statistical analysis, we will find out the depression related features of metabolome and potential biomarkers regulated by XC herb pair which would be described by the regulation of functional networks. And the active compounds will find out through the correlation analysis between chemical components, depressive biomarkers and pharmacodynamics statistics by multiple regression analysis. This study will provide the reliable scientific basis for material basis and compatible regularity of CMP s which have exact clinical efficacy. The study can not only provide a scientific basis for prescriptions containing XC herb pair, but also can provide new ideas and methods of the compatibility and pharmacodynamic substance foundation researches on CMP.

英文关键词： metabonomics;bio-active constituents;compatible regularity of TCM;correlation analysis;antidepressive