Since administration of a powdered extract (TSS) of Danggui-Shaoyao-San (Toki-shakuyaku-san in Japanese) alone to naive mice had no influence on ACh levels in the brain, the present study examined the effect of TSS on the central cholinergic nervous system using mice treated with scopolamine (0.5 mg/kg) or mecamylamine (0.05 mg/kg), which affects the cholinergic nervous system. TSS was suspended in a 5% carboxymethylcellulose solution and mice were orally given single or repeated (twice a day, for 14 days) administration of TSS at 50 or 500 mg/kg. Results on spontaneous locomotor activity showed that (1) single administration of TSS at 50 or 500 mg/kg to naive mice significantly inhibited vertical and horizontal locomotor activities, while repeated administration of TSS at 50 mg/kg significantly stimulated both activities; (2) in mice treated with scopolamine, repeated administration of TSS at 500 mg/kg significantly inhibited the scopolamine-induced increase in locomotor activities, whereas in mice treated with mecamylamine, single or repeated administration of TSS at 50 and 500 mg/kg did not show any influence on the mecamylamine-induced decrease in locomotor activities. Regarding the step-down passive avoidance responses; single administration, but not repeated administration, of TSS at 50 and 500 mg/kg significantly inhibited scopolamine-induced shortening of step-down latency. In mice treated with mecamylamine, TSS did not exert any influence on the step-down latency. As for ACh contents, single or repeated administration of TSS at 50 or 500 mg/kg to naive mice had no influence on the levels of ACh in the cerebral cortex, corpus striatum or hippocampus. However, the levels of brain ACh in mice treated with scopolamine showed a decrease and a single administration of TSS at 500 mg/kg significantly inhibited this scopolamine-induced decrease in ACh levels. These results indicate that TSS ameliorates dysfunction of the central cholinergic nervous system and scopolamine-induced decrease in ACh levels in mouse brain, but has no influence on ACh levels in naive mice. Thus, it suggests that TSS may be a useful therapeutic agent in Alzheimer's disease and senile dementia.

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The effects of the extract powder (CggT) from Chaihu-Guizhi-Ganjiang-Tang (Saiko-keishi-kankyo-to, in Japanese) on the monoamines and their related substances and the acetylcholine in mouse brain were examined. 1) A single administration of CggT significantly increased the levels of HVA and 5-HIAA in the cerebral cortex, hypothalamus, corpus striatum and hippocampus at 75 mg/kg, and those in the hypothalamus, corpus striatum and hippocampus at 750 mg/kg. 2) The repeated administration of CggT significantly increased the level of 5-HT in the hippocampus at 75 mg/kg, and the levels of 5-HT in the corpus striatum and of NE and 5-HT in the hippocampus at 750 mg/kg. 3) The level of ACh was significantly increased in the hypothalamus alone after single administration of CggT. These findings suggest that CggT stimulates function of the dopaminergic and serotonergic nervous systems in mice, but not most of the NEnergic and cholinergic nervous systems.

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