Abstract
Tokishakuyakusan (TS) is one of the prescriptions used for the treatment of female hormonal imbalances in China and Japan. However, its effectiveness and safety are not yet fully understood. This paper reports new observations on the targets of TS, the differences between TS and estrogen, and the potential risks of TS treatment both in vitro and in vivo.
Steroidogenic acute regulatory protein (StAR) and pituitary adenylate cyclase-activating polypeptide (PACAP) were targeted by TS in uterus and pituitary of ovariectomized (OVX) rats. TS had estrogenic activity, but a yeast two-hybrid assay showed that TS did not bind to estrogen receptor α (ERα) and ERβ, whereas 17β-estradiol (E2) did. However, administration of TS to OVX and hypophysectomized (HPX) rats promoted the expression of PACAP mRNA, whereas E2 did not. In addition, histological observations showed that administration of TS promoted development of ovary in HPX rat more effectively than administration of E2+progesterone. Finally, expression of ERα and the progesterone receptor (PR), which is used as a clinical gynecological cancer marker, was tested in the uterus of OVX rats. Administration of TS did not increase expression of ERα and PR, whereas E2 did.
These results indicate that TS targets the expression of StAR and PACAP through different pathways than E2, and it is effective and safe for the treatment of menopausal syndrome in women.
