No abstract

Jujuboside A (JuA), an active saponin, is responsible for the anxiolytic and sedative effects of Zizyphi Spinosae Semen (ZSS). In this study, the gastrointestinal absorption and metabolic dynamics of JuA were investigated in vivo and in vitro. The results showed that the bioavailability was 1.32% in rats, indicating only a trace amount of JuA was able to be absorbed. Further investigation revealed that its poor bioavailability was not caused by malabsorption but by the metabolic process. JuA was hydrolyzed largely in the stomach before being absorbed into the different parts of the intestine (especially duodenum and colon), and the gastric environment played a vital role in this process. Furthermore, the metabolites, jujuboside B (JuB) and jujubogenin, exhibited significant effects on the expression and activation of γ-amino-butyric acid A (GABA(A)) receptors. Our findings demonstrate that the metabolites of the saponin, not the original molecule, should be responsible for the specific bioactivities.

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.

Jujuboside A (JuA), a dammarane-type triterpene glycoside, is a main bioactive saponin in Zizyphi Spinosi Semen (a traditional Chinese herbal food). In this research, the distribution of JuA in Sprague-Dawley rats was investigated with a new and efficient HPLC-ESI-MS=MS method. The results showed that JuA distributed rapidly and widely in various rat tissues (including heart, liver, spleen, kidney, and lung) after intravenous administration. In addition, it was initially found that JuA could pass through the blood-brain barrier and reach various areas of the brain quickly. At 0.25 hr, the concentration of JuA in the hippocampus (204.10 ng Á g À1 ) was significantly higher than in the cerebrum (144.27 ng Á g À1 ), olfactory bulb (98.42 ng Á g À1 ), and corpus striatum (76.04 ng Á g À1 ) (p < 0.05), indicating that the hippocampus was the main accumulation area of JuA in the brain.