Planta Med. 2003 Aug; 69(8): 692-5.

Inhibitory effect of jujuboside a on glutamate-mediated excitatory signal pathway in hippocampus.

Zhang M, Ning G, Shou C, Lu Y, Hong D, Zheng X.

Department of Biomedical Engineering, Zhejiang University, Hangzhou Yuquan, P. R. China.

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 Ca (2+) 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 [Ca (2+)] (i) increase (p < 0.01), and JuA significantly inhibited the Glu-induced Ca (2+) 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.