Administration Of Tokishakuyakusan Research Articles

The traditional kampo medicine tokishakuyakusan increases ocular blood flow in healthy subjects.

The aim of this study was to examine the effects of oral administration of kampo medical formulas on ocular blood flow (OBF). A crossover protocol was used to randomly administer five grams of yokukansan, tokishakuyakusan (TSS), keishibukuryogan, or hachimijiogan to 13 healthy blinded subjects (mean age: 37.3 ± 12.3 years). The mean blur rate, a quantitative OBF index obtained with laser speckle flowgraphy, was measured at the optic nerve head before and 30 minutes after administration. Blood pressure (BP) and intraocular pressure (IOP) were also recorded. No significant changes were observed in mean BP or IOP after the administration of any of the kampo medical formulas. There was a significant increase in OBF 30 minutes after administration of TSS (100% to 103.6 ± 6.9%, P < 0.01). Next, TSS was administered to 19 healthy subjects (mean age: 32.0 ± 11.0 years) and OBF was measured before and 15, 30, 45, and 60 minutes after administration. Plain water was used as a control. OBF increased significantly after TSS administration compared to control (P < 0.01) and also increased from 30 to 60 minutes after administration compared to baseline (P < 0.05). These results suggest that TSS can increase OBF without affecting BP or IOP in healthy subjects.

Induction of regulatory T cells and prolongation of survival of fully allogeneic cardiac grafts by administration of Tokishakuyaku-san in mice

The Japanese herbal medicine Tokishakuyaku-san (TJ-23) has been used to treat neurodegenerative, immune, and respiratory tract diseases, as well as many gynecologic disorders, with few adverse effects. This study investigated the effect of TJ-23 on alloimmune responses in a murine model of cardiac allograft transplantation. CBA mice underwent transplantation of a C57BL/6 heart and received oral administration of 2 g/kg per day of TJ-23 or 1 of 16 other commonly used Japanese herbal medicines from the day of transplantation until 7 days afterward. An adoptive transfer study was conducted to determine whether regulatory cells were generated. Histologic and cell proliferation studies, cytokine measurements, and flow cytometry analyses were also performed. Of the 17 herbal medicines studied, only TJ-23, given in a dose of 2 g/kg per day, induced significantly prolonged allograft survival (median survival time [MST], >100 days). TJ-23 also suppressed proliferation of splenocytes and production of interleukin-2, interleukin-6, and interferon-γ. Adoptive transfer of either whole splenocytes or CD4(+) or CD4(+) CD25(+) cells from TJ-23-treated allograft recipients resulted in indefinite survival of allografts in naive secondary recipients (MST >100 days). Flow cytometry studies showed that the CD4(+) CD25(+) forkhead/winged-helix (FOXP3)(+) regulatory cell population was increased in transplant recipients given TJ-23. TJ-23 induced hyporesponsiveness to fully allogeneic cardiac allografts and generated CD4(+) CD25(+) regulatory cells in our model.

Estrogenic Effects of a Kampo Formula, &lt;i&gt;Tokishakuyakusan&lt;/i&gt;, in Parous Ovariectomized Rats

Female hormone-dependent cancers and other diseases pose a serious health threat for women, and low-risk medicines against such cancers have not yet been discovered. The present study examines the effects of the traditional Chinese herbal mixture, Tokishakuyakusan (TS) and 17beta-estradiol on the uterus of parous ovariectomized rats. Uterine atrophy that causes a reduction in uterine tissue and the uterine cavity area, was induced by ovariectomy, and slightly recovered by the daily oral administration of TS for two weeks (1000 mg/kg body weight). TS restored the decreased plasma estradiol concentration due to ovariectomy. However the yeast two-hybrid assay showed that TS did not bind estrogen receptors alpha and beta and immunohistochemical staining revealed that 17beta-estradiol stimulated the protein expression of estrogen receptor alpha, progesterone receptor, c-fos and c-jun in the uterus, whereas TS did not. These results suggest that TS might be useful for treating menopausal syndromes among women, as well as for patients when hormone replacement therapy (HRT) with estrogen is contraindicated.

Effects of single and repeated administrations of Toki-shakuyaku-san on the concentrations of brain neurotransmitters in mice.

The amounts of monoamine-related substances (NE, MHPG, DA, DOPAC, HVA, 5-HT, and 5-HIAA and acetylcholine (ACh) in the cerebral cortex, corpus striatum and hippocampus of mice treated orally with a powdered extract of Toki-shakuyaku-san (TSS) were measured using the HPLC-ECD method. Single administration of TSS at 50 mg/kg decreased the content of NE in the hippocampus, but increased the contents of DA, DOPAC and HVA. Single administration of TSS at 50 mg/kg increased the contents of DA and HVA in the cerebral cortex and those of DA, DOPAC and HVA in the hippocampus, but decreased the content of NE. Repeated administration (twice a day, for 14 days) of TSS at 50 mg/kg increased the contents of DA, DOPAC and 5-HIAA in the cerebral cortex, while 500 mg/kg increased the contents of NE, MHPG, DOPAC, 5-HT and 5-HIAA in the cerebral cortex, and the NE and DA in the corpus striatum. With regard to ACh content, single and repeated administrations of TSS at 50 and 500 mg/kg had no influence in the three regions of mouse brain. These results suggest that single administration of TSS stimulates the function of the dopaminergic nervous system in the hippocampus in mice and inhabits the function of the adrenergic nervous system, and that repeated administration of TSS stimulates the function of the adrenergic, dopaminergic and serotonergic nervous systems in the cerebral cortex. TSS, however, did not show any influence on the brain ACh content in mice.

The Direct Luteotropic Effect of Tokishakuyakusan in Rats

The effect of Tokishakuyakusan (TS) on the corpus luteum function in pseudopregnant rats was examined in vivo. On day 4 of pseudopregnancy (PSP), induced by cervical stimulation, TS (20 micrograms) stimulated the progesterone secretion rate (PSR) in the ovarian venous plasma. There was also a significant increase in the rate of progesterone to 20 alpha-OH-progesterone. However, on day 8 of PSP, there was no apparent change in PSR in the ovarian venous plasma after the administration of TS. These data suggest that the sensitivity to TS of the corpus luteum varies according to its age.