Abstrait

Jujuboside A promotes the release of adenosine and uridine in the prefrontal cortex of mice by modulating the ENT transporter: in vivo brain microdialysis experiments

Wu Song, Tianzhu He, Min Qian, Lin Wei, Shuang Jiang, Donghui Yue, Zhi Liu

Introduction: Jujuboside A (JuA), as the main active component in the seed of wild jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chow), has been found to have significant sedative, hypnotic and anxiolytic effects, but its mechanism is still unclear. Recent studies show that the endogenous adenosine and uridine in the central nervous system are active substances to promote sleep.

Materials and Methods: The effect of systemic administration and local perfusion of JuA on the release of uridine and adenosine in the prefrontal cortex was investigated by microdialysis in this study, and the locomotor activity of mice was observed. In order to investigate the role of ENT transporter in the JuAinduced release of nucleosides, in which Nitrobenzylthioinosine (NBTI, an ENT inhibitor) was used in combination with JuA.

Results: The systemic administration of JuA (40, 80 mg/kg) could dose-dependently increase the content of extracellular uridine and adenosine in the prefrontal cortex of mice, and decrease their locomotor activities, while the local perfusion of JuA showed no significant effects. The administration of NBTI (10 μM) alone could significantly elevate the content of the extracellular nucleotides, whereas NBTI (10 μM) combined with JuA did not further elevate the content of the nucleotides. The two-way ANOVA analysis showed that NBTI and JuA had a significant interaction.

Conclusion: The systemic administration of JuA can promote the release of uridine and adenosine in the prefrontal cortex of mice, which may be related to the effect of its metabolites on the ENT transporter.