Investigation of the anxiolytic effects of kampo formulations used for used to treat menopausal psychotic syndromes in women

研究了四种汉方制剂：Tokishakuyakusan、Kamishoyosan、Keishibukuryogan和Unkeito的抗焦虑作用。这些汉方制剂用于治疗女性更年期综合征。虽然每种汉方配方的草药成分相似，但这些汉方配方的临床用途不同。因此，我们从基础药理学和化学研究方面探讨了它们之间的差异，通过对这些汉方制剂的比较研究，发现由10种中草药组成的神藏育散（KSS）具有抗焦虑作用。采用雄性小鼠社会互动实验（SI）对KSS及其组成中药进行评价。口服KSS剂量依赖性地增加SI时间。GABA_A/BZP受体拮抗剂氟马西尼可显著阻断KSS对SI时间的影响。此外，5 α-还原酶抑制剂非那肽可明显阻断KSS的作用。当给予除去栀子的KSS提取物（不包括栀子的配方）时，抗焦虑作用显著降低。另一方面，栀子提取物或京尼平苷的给药增加了SI时间。京尼平苷的抗焦虑作用也被氟马西尼和非那匹德阻断。提示栀子和栀子苷在抗焦虑作用中起重要作用，其抗焦虑作用可能是通过刺激GABA_A/BDZ受体介导的，而GABA_A/BDZ受体参与神经甾体的合成。

The anxiolytic effects of four Kampo formulations ; Tokishakuyakusan, Kamishoyosan, Keishibukuryogan, and Unkeito, were investigated. These Kampo formulations ware used to treat menopausal syndromes in wemen. Although the herbal ingredients of each Kampo formula are similar, clinical uses of these Kampo formulations are differents. 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 male mice. Oral administration of KSS dose-dependently increased the SI time. The effect of KSS on SI time was significantly blocked by the GABA_A/BZP receptor antagonist flumazenil. In addition, 5 α-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 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/BDZ receptor stimulation involved in the neurosteroids synthesis.