Jujuboside A in ameliorating insomnia in mice via GABAergic modulation of the PVT

Ethnopharmacological relevance: Ziziphus jujuba var. spinosa (Bunge) Hu ex H. F. Chow (ZSS), a traditional Chinese medicinal herb, has been historically used to treat insomnia and neurological disorders. Jujuboside A, a triterpenoid saponin isolated from ZSS, represents its core bioactive component with purported sedative properties, yet its mechanism of action remains underexplored.

Aim of the study: To validate the anti-insomnia efficacy of Jujuboside A and elucidate its GABAergic regulatory mechanisms through integrated in vivo and in vitro approaches.

Materials and methods: A chronic sleep deprivation mouse model was established using modified multi-platform water environment. Behavioral assessments (open-field test, pentobarbital-induced sleep test) were combined with histopathological analysis (H&E staining), flow cytometry (Apoptosis), ELISA (GABA/Glu quantification), and Western blot (GABA A/GABA B, NMDA/AMPA receptors). Pharmacological inhibition of GABA signaling was performed using GABA-IN-1.

Results: Jujuboside A significantly shortened sleep latency and prolonged sleep duration vs. model group. Histopathology revealed Jujuboside A-mediated restoration of hippocampal neuronal density and mitigation of nuclear pyknosis. Jujuboside An upregulated GABA levels while suppressing Glu and neuronal Apoptosis, with concomitant increases in GABA A and GABA B receptor expression. Crucially, GABA-IN-1 abolished these therapeutic effects, confirming GABA dependency.

Conclusions: Jujuboside A ameliorates insomnia by restoring GABA/Glu homeostasis and enhancing GABA Receptor expression, thereby validating ZSS's traditional use through modern pharmacological evidence.

GABA/Glu homeostasis; Jujuboside A; PV/SST neurons; Paraventricular nucleus of the thalamus; Sleep-wake disorder.