Neuroprotective effect of yokukansan against cytotoxicity induced by corticosterone on mouse hippocampal neurons

Yokukansan, a traditional Japanese herbal medicine, has been used for the management of neurodegenerative disorders and for the treatment of neurosis, insomnia, and behavioral and psychological symptoms of dementia. Recently, several studies have shown that yokukansan has a neuroprotective effect. The aim of this study was to examine the neuroprotective effect of yokukansan on hippocampal neurons from embryonic mouse brain against the effects of corticosterone, which is considered to be a stress hormone and to be cytotoxic toward neurons. The cell survival rates were measured by the WST-8 assay and LDH assay. Twenty-four hours after treatment with corticosterone, cell numbers were significantly decreased compared with the control or treatment with vehicle in a dose-dependent manner. When cells were treated with 30 μM corticosterone, the decrease in the number of cells was significantly recovered by treatment with yokukansan (100-1000 μg/ml) in a dose-dependent manner. However, yokukansan did not suppress the decrease in cell numbers that was induced by treatment with 100 μM corticosterone. In the LDH assay, treatment with yokukansan at a high concentration (500-1000 μg/ml) suppressed the LDH concentration induced by treatment with both 30 μM and 100 μM corticosterone compared to treatment with corticosterone alone, respectively. These results suggest that yokukansan protects against the cytotoxic effect of a low concentration of corticosterone on hippocampal neurons.