Theoretical Basis for Herbal Medicines, Tokishakuyaku‐San and Sairei‐To, in the Treatment of Recurrent Abortion: Enhancing the Production of Granulocyte–Macrophage Colony‐Stimulating Factor in Decidual Stromal Cells

Problem To get insight into the basis for the empirical usage of herbal medicines, such as Tokishakuyaku-san (Toki) and Sairei-to (Sai) in the treatment of recurrent abortion and intrauterine growth restriction, we examined whether these medicines modulate the production of granulocyte–macrophage colony-stimulating factor (GM-CSF), a cytokine working as an important mediator for intercellular communication in the embryonic development, in decidual stromal cells (DSCs). Method of study Human DSCs were cultured with either Toki or Sai at several different concentrations. The effect on cell proliferation was assessed by WST-8 assay. GM-CSF released into culture medium was analyzed using enzyme-linked immunosorbent assay, and semi-quantitative polymerase chain reaction was carried out to see GM-CSF mRNA expression in DSCs. Results Sai inhibited the proliferation of cultured DSCs, while no interference was observed in the presence of Toki. Both Toki and Sai enhanced the release of GM-CSF into culture medium. The amount of GM-CSF mRNA in cultured DSCs was as well increased by either Toki or Sai. Conclusion Considering the significance of GM-CSF in embryonic development, clinical benefit of these herbal medicines in the treatment of recurrent abortion might be based on the shown pharmacological reaction related to GM-CSF.