Wang Mingyu, Wang Gen, Zhao Maoyuan, Hou Lingyun, Ma Dongchuan, Yang Hao, Luo Zhaoliang, Mi Benzhong, Lv Shangbin
Chongqing Academy of Chinese Materia Medical, Chongqing, 400065, China; Chongqing College of Traditional Chinese Medicine, Chongqing, 402760, China.
Obstetrics and Gynecology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400021, China.
J Ethnopharmacol. 2025 Jun 12;349:119939. doi: 10.1016/j.jep.2025.119939. Epub 2025 May 10.
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.
To validate the anti-insomnia efficacy of Jujuboside A and elucidate its GABAergic regulatory mechanisms through integrated in vivo and in vitro approaches.
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.
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.
Jujuboside A ameliorates insomnia by restoring GABA/Glu homeostasis and enhancing GABA receptor expression, thereby validating ZSS's traditional use through modern pharmacological evidence.
酸枣仁（Ziziphus jujuba var. spinosa (Bunge) Hu ex H. F. Chow，ZSS）是一种传统的中药材，历史上一直用于治疗失眠和神经系统疾病。酸枣仁皂苷A是从酸枣仁中分离出的一种三萜皂苷，是其核心生物活性成分，据称具有镇静特性，但其作用机制仍未得到充分研究。
通过体内和体外综合方法验证酸枣仁皂苷A的抗失眠疗效，并阐明其GABA能调节机制。
使用改良的多平台水环境建立慢性睡眠剥夺小鼠模型。行为评估（旷场试验、戊巴比妥诱导睡眠试验）与组织病理学分析（苏木精-伊红染色）、流式细胞术（凋亡检测）、酶联免疫吸附测定（GABA/Glu定量）和蛋白质免疫印迹法（GABAA/GABAB、NMDA/AMPA受体）相结合。使用GABA-IN-1对GABA信号进行药理学抑制。
与模型组相比，酸枣仁皂苷A显著缩短了睡眠潜伏期并延长了睡眠时间。组织病理学显示酸枣仁皂苷A介导了海马神经元密度的恢复和核固缩的减轻。酸枣仁皂苷A上调了GABA水平，同时抑制了Glu和神经元凋亡，并伴随GABAA和GABAB受体表达的增加。至关重要的是，GABA-IN-1消除了这些治疗效果，证实了对GABA的依赖性。
酸枣仁皂苷A通过恢复GABA/Glu稳态和增强GABA受体表达来改善失眠，从而通过现代药理学证据验证了酸枣仁的传统用途。
