Tokishakuyakusan Research Articles

Tokishakuyakusan Stimulates Progesterone and Estradiol-17 β Production by Rat Granulosa Cells and Progesterone, Testosterone and Estradiol-17 β by the Residual Portion of the Follicle in Vitro

To examine the possible effects of Tokishakuyakusan (TS) on steroidogenesis by preovulatory follicles at the cell level, the expressed granulosa cells and remaining portion of follicles from pregnant mare's serum gonadotropin (PMS)-treated immature rats were incubated in vitro with increasing concentrations of TS for 3 h. TS significantly stimulated progesterone and estradiol-17 b production, with a predominant stimulation of progesterone, by the expressed granulosa cells, while testosterone production was not stimulated. In the remaining portion of the follicle, TS also significantly stimulated progesterone, testosterone and estradiol-17 b production. Similar to the effect produced by granulosa cells, the stimulatory effect of TS was stronger on progesterone than on testosterone and estradiol-17 b production. These results suggest that TS has a potent, direct stimulatory effect on steroidogenesis, especially progesterone production, by constituent tissue compartments of rat preovulatory follicles in vitro.

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.

Effects of Herbal Components of Tokishakuyakusan on Progesterone Secretion by Corpus Luteum In Vitro

Twenty-seven-day old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were incubated in vitro with herbal components of Tokishakuyakusan (TS). Mixture of hoelen + peony root + alisma rhizone + Japanese angelica root or hoelen + Japanese angelica root or Japanese angelica root + cnidium rhizome significantly increased progesterone secretion, and these levels tended to exceed the level by TS alone. These results suggest an exquisitely blended effect of herbal components of TS on progesterone secretion by corpora lutea.

Effect of Tokishakuyakusan on Corpus Luteum Endothelin

The presence of endothelin-1 (ET) and effect of Tokishakuyakusan (TS) on ET in rat corpora lutea (CL) was investigated in superovulated ovaries, induced with pregnant mare's serum gonadotropin and human chorionic gonadotropin. A high concentration of ET was found in the CL. The level of ET was significantly lower in the CL from TS-treated rats than that in TS-untreated rats (402.68 versus 575.60 pg/g wet weight, p less than 0.05). In contrast, the ET levels in plasma were by far lower than those in CL. These data indicate an inhibitory effect of TS on ET, an intraovarian peptide, production or accumulation in the CL.

Endothelin-1 Levels are not Influenced by Tokishakuyakusan and Keishibukuryogan Treatment in Women

The effect of Tokishakuyakusan (TS) or Keishibukuryogan (KB) on endothelin-1 (ET-1), a newly identified peptide, in plasma and amniotic fluid from TS- or KB-treated women or normal pregnant women following TS or KB treatment was studied during the menstrual cycle, gestation, delivery and the post-partum period. ET-1 levels during and/or after TS or KB treatment had no significant changes when compared with those in TS- or KB-untreated women. These results suggest that TS or KB has no effects on the ET-1 level during the menstrual cycle, gestation and the post-partum period.

Effects of Tokishakuyakusan and Keishibukuryogan on Steroidogenesis by Rat Preovulatory Follicles in Vivo

The effect of Tokishakuyakusan (TS) and Keishibukuryogan (KB) on estradiol-17 beta, progesterone and testosterone in serum and ovarian tissue from PMS-treated immature rats was examined in vivo. The in vivo intravenous administration of 20 micrograms of TS or KB increased the concentrations of estradiol-17 beta, progesterone and testosterone. These results suggest that TS and KB stimulate in vivo the production of estradiol-17 beta, progesterone and testosterone by preovulatory follicles, and that TS stimulation is more effective than KB.

Neuroendocrine Effect of Toki-Shakuyaku-San on Ovulation in Rats

In this study, the experiments were designed to examine if Toki-Shakuyaku-San (TSS) has a neuroendocrine effect on ovulation. TSS (500 mg/kg Bwt in drinking water) was given to Sprague Dawley immature female rats on 25 days of age and during experimental sessions. Fifteen IU of the hMG (Gonadoryl 4; GNR 4) was injected intraperitoneally on the morning of 28 days of age, and ovulation occurred in 70% of rats on the following day. In TSS drinking immature female rats, administration of GNR 4 on 28 days of age results in ovulation twice: once on 29 days of age and again on 31 days of age. Administration of sodium pentobarbital (Nembutal) at 12:30 p.m. on 28 days of age did not block the first ovulation on 29 days of age, but administration at 12:30 p.m. on 30 days of age blocked the second ovulation on 31 days of age. However, delayed ovulation was observed on 32 days of age. This evidence indicates that GNR 4 acts on the ovary directly and induces first ovulation in TSS treated rats. However, TSS treatment modulates the chain of events in the neuroendocrine control of ovulation and results in the second ovulation.

当帰芍薬散,大黄,電気針治療などの促進作用による排卵と妊娠

当帰芍薬散,大黄,電気針治療などの促進作用による排卵と妊娠

Hachimijiogan and Tokishakuyakusan enhance deoxyribonucleic acid alpha-nucleotidyltransferase activity in relationship to DNA synthesis by ovarian follicles via a cyclic AMP system.

The ovaries resected from twenty-nine day old female rats primed with 10 IU of PMS for 48 hours were incubated for 120 minutes with 2-20 micrograms/ml of Hachimijiogan (HZ) and Tokishakuyakusan (TS). The animals in another group were injected intravenously with 20 micrograms of HZ and TS 48 hours after PMS injection, and 20 minutes later decapitated. Deoxyribonucleic acid (DNA) alpha-nucleotidyltransferase activity and cyclic AMP accumulation in ovarian tissue were significantly increased by HZ and TS. These results suggest that HZ and TS enhance DNA alpha-nucleotidyltransferase activity via cyclic AMP by ovarian follicles.

Tokishakuyakusan stimulates cyclic adenosine 3',5'-monophosphate accumulation and progestin production by corpora lutea.

The effect of Tokishakuyakusan (TS) on rat corpora lutea was examined in vivo and in vitro. In an in vivo study, TS stimulated cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation and steroidogenesis by corpora lutea, induced by PMS and hCG. In an incubation study, TS increased cyclic AMP accumulation and progesterone secretion. These results suggest that TS stimulates the corpora lutea to produce progestins via the mediation of cyclic AMP.