Glyceollins and dehydroglyceollins isolated from soybean act as SERMs and ER subtype-selective phytoestrogens.

Seven prenylated 6a-hydroxy-pterocapans and five prenylated 6a,11a-pterocarpenes with different kinds of prenylation were purified from an ethanolic extract of fungus-treated soybean sprouts. The activity of these compounds toward both human estrogen receptors (hERα and hERß) was determined in a yeast bioassay and the activity toward hERα was additionally tested in an U2-OS based hERα CALUX bioassay. In the yeast bioassay, compounds with chain prenylation showed in general an agonistic mode of action toward hERα, whereas furan and pyran prenylation led to an antagonistic mode of action. Five of these antagonistic compounds had an agonistic mode of action in the U2-OS based hERα CALUX bioassay, implying that these compounds can act as SERMs. The yeast bioassay also identified 8 ER subtype-selective compounds, with either an antagonistic mode of action or no response toward hERα and an agonistic mode of action toward hERß. The ER subtype-selective compounds were characterized by 6a-hydroxy-pterocarpan or 6a,11a-pterocarpene backbone structure. It is suggested that either the extra D-ring or the increase in length to 12-13.5Å of these compounds is responsible for an agonistic mode of action toward hERß and, thereby, inducing ER subtype-selective behavior.

MF101: a multi-component botanical selective estrogen receptor beta modulator for the treatment of menopausal vasomotor symptoms.

INTRODUCTION: The Women's Health Initiative Estrogen Plus Progestin clinical trial demonstrated the risks exceeded the benefits which have led to a decline in menopausal hormone therapy (MHT) by greater than 50%. MHT use was initiated long before there was a significant understanding of the molecular mechanisms of estrogens. It has become clear that the problem with the current estrogens in MHT is they act non-selectively as an agonist in all tissues that contain estrogen receptors. MF101 is an oral, botanically derived extract that was designed to selectively regulate estrogen receptor beta (ERß) because the increased risk of breast and endometrial cancer is due to the activation of estrogen receptor alpha (ERα) by estrogens. Preclinical and clinical data support a role for selective ERß agonists, such as MF101, for vasomotor symptoms without increasing cancer risks. AREAS COVERED: The review covers the biological, pharmacological and clinical advantages of MF101, and the unique ability of MF101 to selectively target the ERß pathway for the treatment of hot flashes (HF). EXPERT OPINION: Preclinical and clinical studies indicate that MF101, a selective estrogen receptor beta agonist, represents a new class of drugs that is safe and effective for treating HF and nighttime awakenings.

Phytoestrogens from Psoralea corylifolia reveal estrogen receptor-subtype selectivity.

The seed of Psoralea corylifolia L. (PCL), a well-known traditional Chinese medicine, has been applied as a tonic or an aphrodisiac agent and commonly used as a remedy for bone fracture, osteomalacia and osteoporosis in China. In our study, the estrogen receptor subtype-selective activities of the extracts and compounds derived from PCL were analyzed using the HeLa cell assay. The different fractions including petroleum ether, CH(2)Cl(2) and EtOAc fractions of the EtOH extract of PCL showed significant activity in activating either ERalpha or ERbeta whereas the n-BuOH fraction showed no estrogenic activity. Further chromatographic purification of the active fractions yielded seven compounds including the two coumarins isopsoralen and psoralen, the four flavonoids isobavachalcone, bavachin, corylifol A and neobavaisoflavone, and the meroterpene phenol, bakuchiol. In reporter gene assay, the two coumarins (10(-8)-10(-5)M) acted as ERalpha-selective agonists while the other compounds (10(-9)-10(-6)M) activated both ERalpha and ERbeta. The estrogenic activities of all compounds could be completely suppressed by the pure estrogen antagonist, ICI 182,780, suggesting that the compounds exert their activities through ER. Only psoralen and isopsoralen as ERalpha agonists promoted MCF-7 cell proliferation significantly. Although all the compounds have estrogenic activity, they may exert different biological effects. In conclusion, both ER subtype-selective and nonselective activities in compounds derived from PCL suggested that PCL could be a new source for selective estrogen-receptor modulators.

Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?

The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet.

[The research of estrogen receptor modulator and correlative Chinese herbs].

OBJECTIVE: To review the study of estrogen receptor modulator and correlative Chinese herbs. METHOD: Based on to the documents in the world, the estrogen receptor modulator and correlative Chinese herbs summarized. RESULT AND CONCLUSION: Estrogen receptor modulator is biological compounds in botany. It can exert faint estrogen-like effects by low affinity with estrogen receptor. Some of the Chinese herbs have the estrogen-like activity, but further and more systemic research work are to be done.