Full text loading...
薬理と治療
Abstract
Background Tokishakuyakusan(TSS)is a Kampo medicine, which has been prescribed to treat infertility. Its precise mechanism of action, however, remains unclear. Leukemia inhibitory factor(LIF)in the endometrium plays an indispensable role in embryo implantation and is linked to infertility or implantation failure. Here, we investigated whether TSS promoted endometrial LIF production and ameliorated implantation failure induced by mifepristone(RU-486)in rats. Methods Human endometrial epithelial HEC-1-A cells were treated with TSS or with 31 compounds derived from the constituent crude drug of TSS for 24 h, and the LIF concentrations in cell culture supernatants were measured. To examine the absorption of active components to the blood, plasma samples after oral administration of TSS were analyzed by liquid chromatography-tandem mass spectrometry(LC︱MS╱MS). The implantation failure rat model was developed by subcutaneous administration of RU-486 on day 3 post-coitus. The rats were fed TSS-containing(1% or 3%)or a control diet from day 13 pre-coitus, and subsequently implantation sites were assessed on day 8 post-coitus. Results TSS significantly enhanced LIF production. Ten components, particularly Levistolide A, Atractylodin, and Tumulosic acid, significantly promoted LIF production. Seven active components, including these three components, absorbed into the blood. RU-486 decreased the number of implantation sites in the uterus of the rats in a dose-dependent manner, and the decrease was significantly alleviated by TSS(3%-diet). Conclusion TSS and several of its active components promote endometrial LIF production and TSS ameliorates implantation failure in rats. These findings highlight the beneficial effects of TSS on infertility.
Data & Media loading...