Post-ischemic treatment with toki-shakuyaku-san (tang-gui-shao-yao-san) prevents the impairment of spatial memory induced by repeated cerebral ischemia in rats.

Previously we have reported that Toki-shakuyaku-san (TSS) ameliorated the impairment of spatial memory induced by single cerebral ischemia (1 x 10 minutes) and scopolamine, a muscarinic receptor antagonist. In this experiment, we studied the effect of TSS on repeated cerebral ischemia (2 x 10 minutes, 1-hour interval) induced impairment of spatial memory and neuronal injury in rats. The 8-day post-ischemic treatment with TSS (30-300 mg/kg) was administered p.o. once per day. TSS dose-dependently prevented the impairment of spatial memory, neuronal death and TUNEL positive cells induced by repeated cerebral ischemia. In order to determine the mechanism of TSS, we also studied the effect of TSS on GluR2 mRNA, one of the glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor subunits. Repeated cerebral ischemia significantly decreased GluR2 flop mRNA at 1 and 3 days after the occlusion. TSS (300 mg/kg) significantly suppressed the decrease in GluR2 flop at 3 days after repeated cerebral ischemia. These results suggested that the TSS has neuroprotective action which may be indirectly mediated by the AMPA receptor, and TSS may be beneficial for the treatment of cerebrovascular dementia.

Determination of the effectiveness of components of the herbal medicine Toki-Shakuyaku-San and fractions of Angelica acutiloba in improving the scopolamine-induced impairment of rat's spatial cognition in eight-armed radial maze test.

The improving effects of various components of Toki-Shakuyaku-San (TSS) and fractions isolated from Angelica acutiloba Radix (Toki) on scopolamine-induced spatial memory impairment were investigated in eight-armed radial maze. The scopolamine-induced memory impairment was characterized by prominent increase of error choices in addition to decreased correct choices. Toki, Cnidium officinale Rhizoma (Senkyu), Poria cocos Hoelen (Bukuryo), Alisma orientale Rhizoma (Takusha), and Atractylodes lancea Rhizoma (Sojutsu) increased the correct choices, while only the Toki, Sojutsu, and Takusha decreased the error choices. No effect was produced by Paeonia lactiflora Radix (Shakuyaku). Investigation of effects of fractions isolated from Toki revealed that its activity mainly resided in the butanol layer and its contents of N-methyl-beta-carboline-3-carboxamide and amines. Moreover, the alkaloid, internal and external solutions (containing poly-, di-, and monosaccharides) obtained by dialysis with Visking cellophane tubing also improved the memory. However, no improving properties were detected for methanol and hexanol layers, L-(-)-tryptophan, L-arginine, L-(-)-lysine, and choline chloride. The results showed that the TSS components could improve the reference and working memory impaired by scopolamine. The improving effect of TSS is produced greatly by the Toki component, the activity of which was greatly produced by the fraction extracted by butanol.

[Effect of cimetidine with chemotherapy on stage IV colorectal cancer].

We herein report the result of a prospective study to investigate the efficacy of cimetidine administration in conjunction with chemotherapy for stage IV colorectal cancer. Sixty-two patients treated with Leucovorin/5-fluorouracil therapy were enrolled from 1996 to 2000. Both groups were well matched for pre-treatment characteristics. There was no difference in survival in cur B patients. However, the cimetidine group had significantly prolonged survival in the patients with cur C or non-resectable carcinoma. This study suggests that cimetidine treatment may improve the survival of patients with non-curative surgery for stage IV colorectal cancer.