Protective effect of Choto-san, Chotoko and its alkaloids on experimental vascular dementia in mice : Elucidation using Morris water maze test

摘要

It has been reported that Choto-san has an effect on treatment of vascular dementia in clinical tests. In the present study, we investigated the effect of Choto-san and its main constituent Chotoko (Uncariae uncis cum ramulus) on the spatial cognitive impairment induced by transient cerebral ischemia in mice in the Morris water maze performance. The spatial cognitive deficiency caused by transient cerebral ischemia in mice exhibited an increase of escape latency and a reduction of swimming time in the platform quadrant. Choto-san (750-6000 mg/kg, p.o.) and Chotoko (75-600 mg/kg, p.o.) administered one hour before the operation shortened the escape latency and increased the swimming time in the platform quadrant, showing a protective effect on the impairment induced by transient cerebral ischemia. Furthermore, we also studied the efficacy of alkaloid fraction, indole alkaloid (geissoschizine methylether) and oxindole alkaloid (rhynchophylline) of Chotoko. The alkaloid fraction (10 mg/kg, p.o.) of Chotoko and rhynchophylline (10 mg/kg, p.o) significantly improved the spatial cognitive impairment induced by transient cerebral ischemia in the Morris water maze, while the protective effect of geissoschizine methylether was weak. These results suggested that Choto-san and Chotoko have a protective effect on transient cerebral ischemia-induced spatial cognitive impairment. The beneficial effect of Chotoko is partly attributed to the oxindole alkaloid rhynchophylline.