New estrogenic compounds isolated from Broussonetia kazinoki.

Two new and two known compounds were identified as estrogenic constituents from Broussonetia kazinoki. Their structures were elucidated as broussonin A (1), tupichinol C (2), kazinol U (3), and (+)-(2R) kazinol I (4). They showed estrogenic activity with ligand-binding activity of estrogen receptor, transcriptional activity of estrogen-responsive element-luciferase reporter genes. They also control the cellular gene expression levels of estrogen-responsive genes. Phytoestrogens from B. kazinoki may have beneficial effects in the treatment of menopausal symptoms.

Caffeic acid phenethyl ester, a component of beehive propolis, is a novel selective estrogen receptor modulator.

Caffeic acid phenethyl ester (CAPE) is an active ingredient of beehive propolis with a structure similar to phenolic acid. The estrogenic effects of propolis were previously demonstrated through the activation of an estrogen receptor. To identify the estrogenic properties of propolis, CAPE was evaluated using in vitro and in vivo methods. CAPE showed selective binding affinity to human estrogen receptor beta (hERbeta) rather than hERalpha. CAPE also reduced ERalpha expression in MCF-7 and MDA 231 cells. In the yeast estrogen receptor transcription assay, CAPE produced the transcriptional activity of estrogen-responsive element with EC(50) values of 3.72 x 10(-6) M. CAPE did not increase the growth of MCF-7 estrogen receptor-positive breast cancer cells in doses ranging from 10(-7) to 10(-5) M. In order to understand how CAPE acts in animals, CAPE was tested by a uterotrophic bioassay. Treatment with CAPE (100, 500 mg/kg) did not increase the uterine weight relative to 3 microg/kg 17beta-estradiol treatment. The results indicate that CAPE, which is a selective agonist to hERbeta, but does not show any estrogenic effect on estrogen receptor-positive breast cancer cells and in immature rat uterine tissue, is a potential selective estrogen receptor modulator.