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Erythrina poeppigiana is a medicinal plant which is widely used in Asia, Latin America, and Africa in traditional remedies for gynecological complications and maladies. In continuation of studies for the discovery of novel phytoestrogens, four erythroidine alkaloids, namely α-erythroidine, β-erythroidine, and their oxo-derivatives 8-oxo-α-erythroidine and 8-oxo-β-erythroidine, were isolated and structurally characterized from the methanolic extract of the stem bark of E. poeppigiana. Due to the high amounts of erythroidines in the extract and considering the widespread utilization of Erythrina preparations in traditional medicine, the exploration of their estrogenic properties was performed. The estrogenicity of the isolated erythroidines was assayed in various estrogen receptor-(ER)-dependent test systems, including receptor binding affinity, cell culture based ER-dependent reporter gene assays, and gene expression studies in cultured cells using reverse transcription polymerase chain reaction techniques. α-Erythroidine and β-erythroidine showed binding affinity values for ERα of 0.015 ± 0.010% and 0.005 ± 0.010%, respectively, whereas only β-erythroidine bound to ERβ (0.006 ± 0.010%). In reporter gene assays, both erythroidines exhibited a significant dose-dependent estrogenic stimulation of ER-dependent reporter gene activity in osteosarcoma cells detectable already at 10 nM. Results were confirmed in the MVLN cells, a bioluminescent variant of MCF-7 breast cancer cells. Further, α-erythroidine and β-erythroidine both induced the enhanced expression of the specific ERα-dependent genes trefoil factor-1 and serum/glucocorticoid regulated kinase 3 in MCF-7 cells, confirming estrogenicity. Additionally, using molecular docking simulations, a potential mode of binding on ERα, is proposed, supporting the experimental evidences. This is the first time that an estrogenic profile is reported for erythroidine alkaloids, potentially a new class of phytoestrogens., (Georg Thieme Verlag KG Stuttgart · New York.)

Cancer is a leading cause of death worldwide, and the numbers of new cancer cases are expected to continue to rise. The main goals of cancer therapy include removing the primary tumor, preventing the spread of distant metastases, and improving survival and quality of life for the patients. To attain these goals of cancer therapy, the combination of different chemotherapeutics, as opposed to the conventional single-agent treatment, is an emerging area of research. Given the potential risks of drug toxicity in such treatment, the focus is to have a second compound that increases the anticancer potential of the primary agent but which reduces toxicity. There is an ever growing interest in treatment with natural compounds, such as plant phytoestrogens, as an adjuvant cancer therapy along with conventional cancer therapy. The question remains whether or not adding these compounds to the cancer therapy regimen as a second agent would be beneficial, and if they are safe to be used among cancer patients. The current literature suggests that phytoestrogen treatment is capable of inducing G2/M cell cycle arrest in a number of cancer cell lines, as well as upregulating cell cycle inhibitory molecules. Phytoestrogen therapy has been shown to inhibit inflammation, angiogenesis and metastases in various IN VIVO tumor models, and pronounced benefits have been observed when combined with radiation therapy. The lack of side effects from phase I and II clinical trials of phytoestrogens in cancer therapy points towards their safety, but to further understand their added benefit clinical studies with large sample sizes are required. We have reviewed the recent research studies in these areas in an attempt to find evidence for their role in cancer therapy as well as safety., (Georg Thieme Verlag KG Stuttgart-New York.)

A UPLC-UV/ELSD method has been developed for analysis of major triterpenoids and formononetin in ACTAEA RACEMOSA L. (family Ranunculaceae) samples. The best results were obtained with an Acquity UPLC BEH C18 (100 mmx2.1 mm, i. d., 1 microm) column system using gradient elution with a mobile phase consisting of water and acetonitrile:methanol (7:3) at a constant flow rate of 0.3 mL/min. Owing to their low UV absorption, the triterpene saponins were detected by evaporative light scattering. Within 5.5 minutes, three main triterpenoid glycosides [cimiracemoside A, 23- EPI-26-deoxyactein, and actein] and an isoflavonoid, formononetin, could be separated, with detection limits of 5, 5, 10, and 0.01 microg/mL, respectively. The method was successfully used to analyze different Actaea racemosa market products as well as to distinguish between two other ACTAEA species. There was a significant variability in the amounts of the selected triterpene glycosides for the products containing black cohosh and rhizomes of black cohosh. The isoflavone formononetin was not detected in the samples analyzed. LC-MS coupled with the electrospray ionization (ESI) interface method is described for the identification of formononetin and triterpenoid glycosides in plant samples and dietary supplements that claim to contain black cohosh and different species of Actaea.

In this study, we assessed the relationships between the structure and estrogenicity of flavonoid derivatives. We evaluated estrogenicity via yeast transactivation assays, E-screen assays, and ER binding assays. Genistein and coumestrol in the yeast transactivation assay and biochanin A, genistein, and equol in the E-screen assay, have been shown to have profound estrogenic activities. Flavonoids, with the exception of biochanin A and daidzein, exhibit more profound selectivity for ER beta than for ER alpha. We compared several flavonoids in terms of estrogenicity, as well as relatively small structural differences including the position of the phenol ring and hydroxy groups, the substitution of hydroxy groups or methoxy groups, the opening of the phenol ring; glycitein vs. 4',6,7-trihydroxyisoflavone, biochanin A vs. genistein, apigenin vs. genistein, 7,4'-dihydroxyflavone vs. isoliquiritigenin. A quantitative structure-activity relationship study design was utilized to develop model equations for the estrogenic activities of flavonoid derivatives. The prediction of estrogenicity with regard to ER alpha shows a positive correlation with MW and AlogP, and a negative correlation with Apol and Area (r2 = 0.89 and q2 = 0.83). The prediction of estrogenicity with regard to ER beta reveals a positive correlation with the AlogP and Hbond acceptors, and a negative correlation with RadOfGyration (r2 = 0.77 and q2 = 0.72).

Fractionation of the neutral extract of Onobrychis ebenoides (Leguminosae) yielded a new isoflavone, named ebenosin (1), in addition to the known ones, afrormosin (2), formononetin (3) and daidzein (4). Although the relative binding affinities of 1 - 4 for estrogen receptor alpha (ERalpha) were nearly comparable and matched those of 1-3 for ERbeta, that of 4 for the latter receptor was significantly higher than any of the other. Compounds 1 - 4 induced cell proliferation and gene expression in breast and endometrial cancer cells in an ER-dependent manner. Nonetheless, the rank order of induction potencies ( 4 > 3 >or= 2 >or= 1) matched better that of affinities for ERbeta ( 4 > 3 >or= 2 >or= 1) rather than ERalpha ( 4 >or= 3 >or= 2 >or= 1). While the antiestrogen ICI 182,780 could inhibit the induction of proliferation of ER-positive breast cancer cells by 1-4, it could not prevent 1 from exhibiting significant ER-independent cytotoxicity at 10 microM. By contrast, 1 was much less cytotoxic and only weakly estrogenic for ER-positive endometrial adenocarcinoma cells. In conclusion, our data suggest that the C-8 isoprenyl substituent of 1 renders it cytotoxic and/or estrogenic in a cell-dependent manner.