Gastrointestinal Absorption and Metabolic Dynamics of Jujuboside A, A Saponin Derived from the Seed of Ziziphus jujuba

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.

Determination of ϒ-aminobutyric acid (GABA) in jujube fruit (Ziziphus jujuba Mill.)

“…DW) (Pu, Ding, Zhang, Jiang, & Liu, 2017). The total content of JuA and JuB was less than 0.8 mg.g −1 in jujube fruit reported by Zhao, Li, Yang, Li, and Wang (2006), and the dosage for sedative effect has been reported to be either 40 mg.kg −1 , 25 mg.kg −1 or 9 mg.kg −1 reported by Jiang et al (2007), Song et al (2017) and Cao et al (2010), respectively. If the data of saponins content (0.8 mg.g −1 ) and the dosage (9 mg.kg −1 ) were adopted to calculate the suitable amount of jujube consumption, a person (about 80 kg) should eat at least 0.9 kg jujube fruit for achieving a sedative effect.…”

“…This is far more than the normal consumption amount (about 0.1 kg), so we inferred that the sedative effects of jujube fruit should probably be attributed to other components, rather than saponins. Sedative effects related to the expression and activation of γ-amino-butyric acid A (GABA(A)) receptors (Song et al, 2017), and γ-aminobutyric acid (GABA) is well established as the primary inhibitory transmitter acting at ionotropic GABA A receptors (Bowery 2006). So, we speculated that the sedative effect of jujube fruit might be related to GABA.…”

“…Jujubosides were reported to be responsible for the anxiolytic and sedative effects (Cao et al, 2010). In a more recent paper, it was reported that jujuboside A, jujuboside B and jujubogenin exhibited significant effects on the expression and activation of γ-amino-butyric acid A (GABA(A)) receptors, which accordingly resulted in sedative effect on Sprague−Dawley (SD) rats (Song et al, 2017). It makes us wonder how much fruit should be eaten to achieve a sedative effect.…”

The preparation and investigation of spinosin–phospholipid complex self-microemulsifying drug delivery system based on the absorption characteristics of spinosin

“…The removed perfusate was centrifuged at 7670 g and then filtered through a 0.45‐μm pore filter. The content of spinosin and phenol red in the filtrate was measured …”

“…Blood samples were obtained from the postorbital venous plexuses at 0.5, 1, 2, 5, 8, 12, 18, 24 and 36 h after dosing. The treatment of the plasma samples and calculation of pharmacokinetic parameters referred to the previous study in our laboratory …”