Degradation Kinetics of Jujuboside B by Rat Intestinal Flora In vitro with an RRLC-MS-MS Method

Abstract

Jujuboside B (JuB) is a main bioactive saponin constituent of Ziziphi Spinosae Semen, which is a traditional herb for the treatment of insomnia and anxiety. However, the detailed metabolic mechanism of JuB is poorly understood. In this study, a novel method of rapid resolution liquid chromatography-triple quadrupole mass spectrometry was developed and validated for the analysis of JuB. With the method, the degradation kinetics of JuB by rat intestinal flora in vitro was investigated. The analysis was performed with an Agilent Eclipse Plus C18 (2.1 mm × 50 mm, 1.8 μm) column and an aqueous mobile phase (containing 0.1% formic acid) modified by methanol. The analyte was measured by multiple reaction-monitoring (MRM) modes with m/z 1043.3 → m/z 749.2. This method was validated with perfect accuracy, precision and limit of quantitation. It showed that jujuboside B (JuB) degradation started slowly as incubation with rat feces. The rate constant was correlated greatly with the concentration of sample solutions. Furthermore, some metabolites were elucidated with their chromatographic behavior and typical fragment ions. The results might help better interpret the metabolic and pharmacological mechanism of JuB.

Comparative pharmacokinetics of six major compounds in normal and insomnia rats after oral administration of Ziziphi Spinosae Semen aqueous extract

“…JuA was previously reported to be first hydrolyzed to JuB in the intestinal segments. Thereafter, JuB could be further metabolized to jujubogenin in vitro by rat intestinal bacteria [ [28] , [29] , [30] ].…”

Identification of the absorptive constituents and their metabolites in vivo of Ziziphi Spinosae Semen by UPLC–ESI–Q‐TOF–MS/MS

“…As for metabolites of triterpene glycosides, previous pharmacokinetic studies showed that the oral bioavailabilities of jujuboside A and jujuboside B in rats were only 1.3 and 3.6%, respectively (Liu et al, 2012; Zheng et al, 2015). Jujubogenin, an aglycone of jujuboside, was formed by enzyme hydrolysis owing to intestinal flora, which should be responsible for the specific bioactivities of jujuboside (Song et al, 2017; Zhang, Xie, et al, 2014; Zhang, Zhang, et al, 2014). Otherwise, we previously found that organic acid can transform jujubogenin into the ebelin lacone form owing to a ketal unit at C‐16.…”

Antidepressant-like effect of the saponins part of ethanol extract from SHF

“…In our previous studies, SHF showed antidepressant-like effects and contained jujuboside A and jujuboside B (Liu et al, 2012). Jujuboside A and jujuboside B are the main bioactive compounds of semen Ziziphi Spinosae with sedative activity (Zhang et al, 2013). Betulinic acid has been reported to produce an antidepressant-like effect in TST (Machado et al, 2013).…”