Sleep Aid Effect and Mechanism of Semen Zizyphi Spinosae Extract Enriched With Jujuboside and Jujubogenin in...

The jujuboside in semen zizyphi spinosae has various biological activities beneficial to human health, but its natural content is relatively low, which limits its application in biomedicine and health care. This study employed ultrasonic-assisted alcohol extraction to isolate jujuboside from semen zizyphi spinosae, and the content significantly increased by 482.14%. By treating the extract with β-glucosidase, the content of jujubogenin increased by 6.34%. The extract treated with β-glucosidase had a better sleep improvement effect (86.54%) on sleep-deprived zebrafish than the untreated extract (44.64%). Its sleep improvement effect was 32.24% and 34.99% of γ-aminobutyric acid (GABA) and estazolam, respectively, and did not show any drowsiness similar to the positive controls. The extracts effectively restored the daytime awakening activity of sleep-deprived zebrafish and notably increased levels of GABA, hypocretin/orexin (HCRT), and neuromedin U (NMU). The sleep-regulatory mechanisms of jujubogenin and jujuboside in the extracts of semen zizyphi spinosae may be associated with the expression of GABA receptor subtypes and related genes in GABAergic, HCRTergic, and NMU systems. The research findings indicated that enrichment of jujuboside in semen zizyphi spinosae and utilization of β-glucosidase to further enhance the content of jujubogenin are of great significance for the treatment of insomnia and promoting rehabilitation.