Estrogenic activity of triterpene glycosides in yeast two-hybrid assay

Estrogenic potency of six triterpene glycosides, Holothurin A, Holotoxin A₁, Frondoside A, Cucumarioside A₂-2 and Cauloside C, that are natural products and semi-synthesized Ginsenoside-Rh₂, were examined with yeast two-hybrid system, including expressed genes of human estrogen receptor, hER, the co-activator TIF2 and lacZ as a reporter gene. Only Ginsenoside-Rh₂ exhibited significant moderate estrogenic activity in the concentration range of 10⁻⁷ to 10⁻⁶ M. Its effect was approximately 30% of the activity of 17β-estradiol applied at half-effective concentration. This indicates Ginsenosides-Rh₂ is a weak phytoestrogen. The sea cucumber triterpene glycosides, Holothurin A, Holotoxin A₁, Cucumarioside A₂-2 and Frondoside A, and plant glycoside Cauloside C had no appreciable estrogenic activity. Data obtained by yeast two-hybrid assay reflect structure–activity relationship between tested compounds and 17β-estradiol. Only Ginsenoside-Rh₂ has some similarity in chemical structure with 17β-estradiol that might explain affinity of this glycoside to the hER receptor.