Estrogenic activity of osthole and imperatorin in MCF-7 cells and their osteoblastic effects in Saos-2 cells

There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy(HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase(ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor(PR) and PS2 m RNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis.

Estrogenic activities of two synthetic pyrethroids and their metabolites

Synthetic pyrethroids （SPs） are among the most common pesticides in current use, and so far, several SPs have been assessed for their potential estrogenicities by various methods. Previous studies have shown that the estrogenicities partly come from their metabolites. Although considerable information is available with respect to the metabolism and environmental degradation of SPs, little is known about the estrogenicities of the metabolites. In this study, permethrin （PM） and β-cypermethrin （CP）, as well as their metabolites （3-phenoxybenzoic alcohol （PBCOH）, 3-phenoxybenzaldehyde （PBCHO） and 3-phenoxybenzoic acid （PBCOOH） were evaluated for their estrogenic activities in the MCF-7 human breast carcinoma cell line. In the MCF-7 cell proliferation assay, PM and CP exhibited significant estrogenic activities at 10-7 mol/L, comparable to 17β-estradiol （E2） of 10-9 tool/L, with the relative proliferative effect ratios of 55.4% and 56.3%, respectively. The real-time quantitative polymerase chain reaction （qRT-PCR） results confirmed the estrogenicities of PM and CP with significant alteration of pS2 and ERα mRNA levels observed at 10-6 mol/L. For the three major metabolites, PBCOH and PBCOOH exhibited estrogenic activities in all assays, while no significant estrogenic responses was observed for PBCHO compared to the vehicle control. In particular, PBCOH had even slightly stronger estrogenic activity than its parent compounds, indicating that metabolism may be one of the reasons for the estrogenicities of the SPs. Given the widespread use of SPs, the toxicological effects of parent compounds and their metabolites should be taken into consideration in the risk assessment of SPs.

Medical applications of phytoestrogens from the Thai herb Pueraria mirifica

Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to Thailand.It has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years.Indeed,it has been claimed that P.mirifica contains active phytoestrogens(plant substances with estrogen-like activity).Using high performance liquid chromatography,at least 17 phytoestrogens,mainly isoflavones,have been isolated.Thus,fairly considerable scientific researches,both in vitro in cell lines and in vivo in various species of animals including humans,have been conducted to date to address its estrogenic activity on the reproductive organs,bones,cardiovascular diseases and other climacteric related symptoms.The antioxidative capacity and antiproliferative effect on tumor cell lines have also been assessed.In general,P.mirifica could be applicable for preventing,or as a therapeutic for,the symptoms related to estrogen deficiency in menopausal women as well as in andropausal men.However,the optimal doses for each desirable effect and the balance to avoid undesired side effects need to be calculated before use.