Effects of Kampo medicine, Toki-shakuyaku-san (Tang-Kuei-Shao-Yao-San), on choline acetyltransferase activity and norepinephrine contents in brain regions, and mitogenic activity of splenic lymphocytes in ovariectomized mice

Abstract

We investigated the effects of Toki-shakuyaku-san (TSS, Tang-Kuei-Shao-Yao-San in Chinese), Japanese traditional herbal medicine, on the nervous and immune systems in ovariectomized mice as a climacteric disorder model. Female C57BL/6 mice were ovariectomized (OVX) and TSS was given daily through the drinking water for either 10 or 20 days from the day after ovariectomy. After completion of experimental sessions, animals were sacrificed and specific brain regions were assayed for choline acetyltransferase (ChAT) activity and norepinephrine contents. The mitogenic activities, alkaline phosphatase activity and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H terazolium bromide (MTT) activity, in splenic lymphocytes has also measured. Furthermore, the effects of TSS on learning and memory ability were studied by the step-through type passive avoidance test. As the results, the administration of TSS significantly suppressed the decrease of ChAT activity in the cerebral cortex (CC) and the dorsal hippocampus (DH) of ovariectomized mice at 10 days after ovariectomy, however no significant effect was observed at 20 days after ovariectomy. Norepinephrine contents in OVX group were decreased at 10 and 20 days after ovariectomy in the CC and the ventral hippocampus (VH). The administration of TSS significantly suppressed the decrease of norepinephrine contents at 20 days after ovariectomy. The mitogenic activities of lymphocyte in spleen were increased at 10 days after ovariectomy, and decreased at 20 days after ovariectomy. However, the suppression of these changes was observed in the group given TSS. The mean latent period was also shortened in the passive avoidance test in the OVX group, but TSS treated group improved mean latency. From these observations, it is inferred that administration of TSS brings on the synthesis of acetylcholine and norepinephrine in the CC and hippocampus, and may improve the memory related behavior and the abnormalities in lymphocytes in the models of the climacteric disorder.