基于灰色关联分析方法研究炒酸枣仁镇静催眠作用谱效关系

目的采用基于灰色关联分析方法的谱效相关研究手段筛选炒酸枣仁Ziziphi Spinosae Semen发挥镇静催眠作用的药效物质基础。方法 ip对氯苯丙氨酸建立大鼠失眠模型,造模结束后ig给予炒酸枣仁水煎液,分别于给药后不同时间点采集各实验组大鼠大脑皮层、下丘脑及血浆样品,采用酶联免疫试剂盒方法测定相关药效指标,建立各个药效指标的效应-时间曲线;同时利用UHPLC-Q-TOF-MS分析技术对其中化学成分进行监测,建立各成分的响应强度-时间曲线,使用灰色关联统计方法,对各药效指标的效应-时间曲线与各成分的响应强度-时间曲线分别进行拟合,计算得到各成分与药效的相关度,再将代谢产物归属为原型化学成分,进行权重计算,得到相关系数,并进行排序,客观反映炒酸枣仁水煎液中化学成分与药效的动态发展过程和内在联系。结果于大鼠大脑皮层、下丘脑及血浆中共发现药物相关移行成分23种,其中7种为原型成分,16种为代谢产物。灰色关联分析结果表明,斯皮诺素、山茶苷B、6′′′-阿魏酰斯皮诺素、维采宁-2、莲心季铵碱、去甲异紫堇定、酸枣仁碱F、白桦脂酸共8种化学成分的相关系数较高。结论推测斯皮诺素、山茶苷B、6′′′-阿魏酰斯皮诺素、维采宁-2、莲心季铵碱、去甲异紫堇定、酸枣仁碱F、白桦脂酸为炒酸枣仁发挥镇静催眠作用的主要化学物质基础。

Spectrum-effect relationship study on parched Ziziphi Spinosae Semen for its sedative and hypnotic effects based on gray correlation analysis

Objective To find out the main chemical materials for sedative and hypnotic effects in parched Suanzaoren (Ziziphi Spinosae Semen, ZSS) decoction using spectrum-effect relationship based on gray correlation analysis. Methods The model of insomnia rats was established by intraperitoneal injection of p-chlorophenylalanine. After molding, decoction of parched ZSS was given by ig administration. The cerebral cortex, hypothalamus and plasma samples of rats in each group were collected, to be used for determination of pharmacodynamic indexes. The pharmacodynamic efficacy-time curves were established. Meanwhile, the chemical constituents were detected by UHPLC-Q-TOF-MS method, in which way the intensity-time curves of chemicals were obtained. The efficacy-time curves and intensity-time curves were finally fitted by gray correlation analysis. The correlation degree between each component and pharmacodynamic index was calculated and sorted, so as to reflect the dynamic development process of each component and pharmacodynamic index objectively. Results A total of 23 chemical constituents were found in cerebral cortex, hypothalamus and plasma in all, among which seven were prototype components and 16 were metabolites. The results of gray correlation analysis showed that the correlation coefficients of spinosin, camelliaside B, 6''-feruloylspinosin, vicenin-2, lotusine, norisocorydine, sanjoinine F, and betulinic acid were relatively higher. Conclusion It was speculated that spinosin, camelliaside B, 6''-feruloylspinosin, vicenin-2, lotusine, norisocorydine, sanjoinine F and betulinic acid might be the main chemical materials in parched ZSS to exert sedative and hypnotic effects.