Zhang Mu, Ning Gangmin, Shou Caihua, Lu Yinjun, Hong Dihui, Zheng Xiaoxiang
Department of Biomedical Engineering, Zhejiang University, Hangzhou Yuquan, PR China.
Planta Med. 2003 Aug;69(8):692-5. doi: 10.1055/s-2003-42786.
Jujuboside A (JuA) is a main component of jujubogenin extracted from the seed of Ziziphus jujuba Mill var spinosa (Bunge) Hu ex H F Chou (Ziziphus), which is widely used in Chinese traditional medicine for the treatment of insomnia and anxiety. Previously, we reported the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, the present study was carried out to examine the effects of JuA on glutamate (Glu)-mediated excitatory signal pathway in hippocampus. Microdialysis coupled with high-performance liquid chromatography (HPLC) was used to monitor the changes of Glu levels in the hippocampus induced by penicillin sodium, or a mixture of penicillin sodium and JuA. The results showed that penicillin increased the hippocampal Glu concentration (p < 0.01) and a high dose of JuA (0.1 g/L) significantly blocked penicillin-induced Glu release (p < 0.05). Moreover, the effect of JuA on intracellular Ca2+ changes after the stimulation by Glu was studied in cultured hippocampal neurons with confocal laser scanning microscope (CLSM). It was found that Glu (0.5 mM) induced an intracellular [Ca2+]i increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca2+ increase. The calmodulin (CaM) antagonist trifluoperazine (TFP) showed a similar inhibitory effect as JuA. These observations suggested that JuA has inhibitory effects on Glu-mediated excitatory signal pathway in hippocampus and probably acts through its anti-calmodulin action.
酸枣仁皂苷A（JuA）是从酸枣（鼠李科枣属植物酸枣亚种）种子中提取的酸枣仁皂苷元的主要成分，酸枣在中医中广泛用于治疗失眠和焦虑。此前，我们报道了JuA在体内和体外对海马结构的抑制作用，本研究旨在探讨JuA对海马中谷氨酸（Glu）介导的兴奋性信号通路的影响。采用微透析结合高效液相色谱（HPLC）法监测青霉素钠或青霉素钠与JuA混合物诱导的海马中Glu水平的变化。结果显示，青霉素可增加海马Glu浓度（p < 0.01），高剂量的JuA（0.1 g/L）可显著阻断青霉素诱导的Glu释放（p < 0.05）。此外，利用共聚焦激光扫描显微镜（CLSM）研究了JuA对Glu刺激后培养海马神经元细胞内Ca2+变化的影响。发现Glu（0.5 mM）可诱导细胞内[Ca2+]i升高（p < 0.01），而JuA可显著抑制Glu诱导的Ca2+升高。钙调蛋白（CaM）拮抗剂三氟拉嗪（TFP）显示出与JuA相似的抑制作用。这些观察结果表明，JuA对海马中Glu介导的兴奋性信号通路具有抑制作用，可能通过其抗钙调蛋白作用发挥作用。
