五味子醇提物的化学-药代-药效指纹图谱研究(英文)  

Chemical-pharmacokinetic-pharmacodynamic fingerprints of Schisandra chinensis alcoholic extract

作　　者：王宝莲 扈金萍 盛莉 陈晖 李燕 

机构地区：[1]中国医学科学院药物研究所,天然药物生物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2013年第5期734-740,共7页Acta Pharmaceutica Sinica

基　　金：Project supported by the National Natural Science Foundation of China(Grant 81072696);the National Science and Technology Major Project of China(Grant 2012ZX09301002-001-007)

摘　　要：本研究建立五味子醇提物的化学-药代-药效指纹图谱,通过分析比较三者的相关性和差异以解释五味子体内作用的物质基础。研究采用大鼠肝微粒体体外温孵、正常和CCl4急性肝损伤模型大鼠,以五味子醇甲、酯甲、甲素和乙素作为参比化合物,应用HPLC-UV-MS方法建立五味子醇提物的化学、体外代谢、体内药代和药效指纹图谱。结果表明,五味子醇提物中可检测到4种参比化合物,且含量较高。五味子4种木脂素和醇提物在大鼠肝微粒体中是依赖NADPH的生物转化过程。大鼠口服五味子醇提物后多种活性成分可吸收入体内并生成多个代谢产物,是其保肝作用的物质基础。五味子醇提物不同指纹图谱中均含有的五味子醇甲、酯甲、甲素和乙素可作为"体内暴露"的"PK Marker";代谢产物7,8-dihydroxy-schizandrin和相对分子质量为432的另一代谢物可作为"DM Marker"。本文结果为后续五味子有效成分的代谢转化、作用的物质基础及相关机制研究提供了重要信息。It is valuable to establish a chemical-pharmacokinetic （PK）-pharmacodynamics （PD） fingerprint of traditional Chinese medicine （TCM） for comprehensively understanding the TCM integrated conception and revealing the material foundation. The chemical, metabolic in vitro, and PKJPD in vivo fingerprints of Schisandra chinensis （SC） alcoholic extract were established and comparatively analyzed using HPLC-UV-MS method, rat liver microsomes in vitro and CCl4 intoxicated rats in vivo. Four known effective lignans, schisandrin, schisantberin A, deoxyschizandrin and y-schisandrin, were detected as the standard references in SC alcoholic extract with high concentration. SC alcoholic extract and four lignans when incubated with rat liver microsomes produced several metabolites in NAPDH-dependent manner. Chemical fingerprint of some components with bioactivities were also identified in PK and PD fingerprints in normal and ALl rats that explained the material foundation of SC alcoholic extract for multiple pharmacological effects. Schisandrin, schisantherin A, deoxyschizandrin and 7-schisandrin could be considered as the ＂PK marker＂ of SC alcoholic extract or its relevant preparations, while two metabotites of the four lignans, 7, 8-dihydroxy-schizandrin and another one （Mw 432）, could be recognized as drug-metabolism （DM） Marker. This work provides experimental data for the further studies of metabolism or material foundation of SC components.

关 键 词：五味子 指纹图谱 药代动力学 药效动力学 

分 类 号：R969[医药卫生—药理学]