基于UPLC-Q-TOF/MS分析炙甘草汤体内成分及心脏组织分布特征

Identification of in vivo Components and Distribution Characteristics in Rats' Cardiac Tissues of Zhigancao Decoction by UPLC-Q-TOF/MS

  • 摘要:
    目的 探究炙甘草汤的体内药效物质基础,为其在现代临床的合理应用与开发提供科学依据。
    方法 给Wistar大鼠灌胃炙甘草汤水煎液12.15 g·kg-1后,采集10个时间点(给药后5、15、30、60、120、240、360、480、600、720 min)的大鼠血浆样本和给药后12 h的大鼠心脏(心房、心室)组织样本,应用超高效液相色谱-四极杆飞行时间质谱(UPLC-Q-TOF/MS)技术,对炙甘草汤含药血浆及给药心脏样本进行定性分析,并关注其体内分布特征,同时,绘制炙甘草汤入血成分时间曲线图,观察药物及代谢产物的血药浓度变化。
    结果 从炙甘草汤血浆样本中辨识出了11个原型成分(益母草苷、烟花苷、异夏佛塔苷、对香豆酸、地黄苦苷元、对羟基苯甲酸、7, 4′-二羟基黄酮、毛蕊异黄酮、3′, 4′, 7-三羟基黄酮、半夏酸、吐昔酸)和7个代谢产物,主要为黄酮(苷)类、有机酸类和环烯醚萜苷类等,从心脏样本中(心房和心室同)辨识出了6个原型成分(益母草苷、异夏佛塔苷、地黄苦苷元、7, 4′-二羟基黄酮、甘草素、3′, 4′, 7-三羟基黄酮)和3个代谢产物。代谢途径主要为I相代谢和葡萄糖醛酸化。
    结论 初步确定了炙甘草汤入血及心脏组织成分的原型成分及代谢产物,为炙甘草汤药效物质解析及其药效成分在心脏组织中的研究提供了参考依据。

     

    Abstract:
    OBJECTIVE To deeply explore the in vivo pharmacodynamic substance basis of Zhigancao Decoction, a classic traditional Chinese medicine formula, and provide scientific evidence for its rational application and development in modern clinical practice.
    METHODS Wistar rats were treated with 12.15 g ·kg-1 Zhigancao Decoction by gavage. Rat plasma samples were collected at 10 time points (5, 15, 30, 60, 120, 240, 360, 480, 600 and 720 min after administration) and rat heart (atrial and ventricular) tissue samples were collected at 12 h after administration. Components in the plasma and heart samples were qualitatively identified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and the distribution characteristics of Zhigancao Decoction in vivo were analyzed. At the same time, the time-concentration curve of the prototype components and metabolites in Zhigancao Decoction was drawn to observe the changes of blood drug concentration.
    RESULTS A total of 11 prototype components (Ajugol, Nicotiflorin, Isoschaftoside, 4-Hydroxycinnamic acid, Rehmapicrogenin, 4-Hydroxybenzoic acid, 4′, 7-Dihydroxyflavone, Calycosin, 3′, 4′, 7-Trihydroxyflavone, Pinellic acid, Truxillic acid) and 7 metabolites were identified from the plasma samples of Zhigancao Decoction, mainly including flavonoids (flavonoids glycosides), organic acids, and iridoid glycosides, etc. Additionally, 6 prototype components (Ajugol, Isoschaftoside, Rehmapicrogenin, 4′, 7-Dihydroxyflavone, Liquiritigenin, 3′, 4′, 7-Trihydroxyflavone) and 3 metabolites were identified from the cardiac samples (the atrium and the ventricle showed the same results). The metabolic pathways mainly involved Phase Ⅰ metabolism and glucuronidation.
    CONCLUSION The prototype components and metabolites in plasma and heart tissue of Zhigancao Decoction is preliminarily determined, providing a reference for analyzing the active components of Zhigancao Decoction in heart tissue.

     

/

返回文章
返回