Investigation of the anxiolytic effects of Kampo formulation, Kamishoyosan, used for treating menopausal psychotic syndromes in women

Abstract

The anxiolytic effects of four Kampo formulations (Japanese traditional herbal medicines): Tokishakuyakusan, Kamishoyosan, Keishibukuryogan, and Unkeito, were investigated. These Kampo formulations ware used to treat menopausal syndromes in women. Although the herbal ingredients of each Kampo formula are similar, clinical uses of these Kampo formulations are different. Therefore we investigate the differences of them from the basic pharmacological and chemical studies.From the comparative study of these Kampo formulations, we found the anxiolytic effects of Kamishoyosan (KSS), consists of ten crude herbal drugs. KSS and its composed herbs were assessed by the social interaction (SI) test in mice. Oral administration of KSS dose-dependently increased the SI time. The effect of KSS on SI time was significantly blocked by the gamma- amino-butyric acid A / benzodiazepine (GABA(A)/BZP) receptor antagonist flumazenil. In addition, 5(x-reductase inhibitor finasteride markedly blocked the effect of KSS. When the extract of KSS minus Gardeniae Fructus (the formulae excluding Gardeniae Fructus) was administered, the anxiolytic effect was significantly decreased. On the other hand, the administration of the extract of Gardeniae Fructus or geniposide, major chemical component, increased the SI time. The anxiolytic effect of geniposide was also blocked by flumazenil and finasteride. These findings suggest that Gardeniae Fructus and geniposide have important roles in the anxiolytic effect of KSS, and their anxiolytic effects are mediated by GABA(A)/BZP receptor stimulation involved in the neurosteroids synthesis.