Egonol gentiobioside and egonol gentiotrioside from Styrax perkinsiae promote the biosynthesis of estrogen by aromatase.

Estrogen deficiency is associated with a variety of diseases, including osteoporosis, atherosclerosis, and Alzheimer's disease. Aromatase cytochrome P450 is the only enzyme in vertebrates known to catalyze the biosynthesis of estrogens from androgens. Inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer. However, small molecular agonists of aromatase, which would be useful to locally promote estrogen biosynthesis for the prevention of estrogen deficiency-induced diseases, are rarely reported. In this study, we established a nonradioactive assay for measuring aromatase activity by using human ovarian granulosa KGN cells and identified two estrogen biosynthesis-promoting compounds, egonol gentiobioside and egonol gentiotrioside from Styrax perkinsiae. The compounds also promoted estrogen biosynthesis in 3T3-L1 preadipocyte cells. Further study showed that neither compound affected the transcriptional and translational expression of aromatase in KGN cells, but that both significantly promoted the in vitro enzyme activity of recombinant expressed aromatase. Egonol gentiotrioside was also found to increase the serum estrogen level in ovariectomized rats. These results suggest that these two compounds may promote estrogen biosynthesis through the allosterical regulation of aromatase activity. Egonol gentiobioside and egonol gentiotrioside are, therefore, valuable targets for structural modification and warrant further investigation for their potential as novel pharmaceutical tools for the prevention of estrogen deficiency-induced diseases.