Jujuboside A in ameliorating insomnia in mice via GABAergic modulation of the PVT
Mingyu Wang, Genxu Wang, Maoyuan Zhao, Lingyun Hou, Dan Ma, Hao Yang, Zhaoliang Luo, Bhanger Mi, Shangbin Lv
Abstract
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.