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.