• Toxicological Research
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• v.18 no.4
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• pp.393-396
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• 2002

This study was carried out to evaluate the ostrogenic/antiandrogenic activity of Puerariae Radix in Sprague-Dawley rats. It has known that diverse phytoestrogen were included in some Puerariae Radix, especially in Pueraria mirifica. The Uterotrophic assay and Hershberger assay were performed to evaluate the ostogenic/antiandrogenic activity of various Puerariae Radix (Pueraria thunbergiana, Pueraria mirifica and Butea superba). In Uterotrophic assay, the extracts of Puerariae Radix were administered subcutaneously to immature female SD rats from 19 to 21 days of age. The wet uterus and vaginal weighs significantly increased in the group only treated with extracts of Pueraria mirifica. But, in Hersh-berger assay, all extracts of Puerariae Radix did not show any effects in the castrated rats. These results suggest that Pueraria mirifica has not undrogenic/antiandrogenic effect but potent estrogenic effect. It is possible that components of Pueraria mirifica may act as endocrine disruptor in human body.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.166-166
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• 2002

In the present study, estrogenic or antiestrogenic activity of cypermethrin, a pyrethroid insecticide was investigated. We used immature rat uterotrophic assay, estrogen-responsive calbindin-D9k (CaBP-9k) gene expression assay and luciferase reporter gene assay for measure of estrogenic potential of cypermethrin.(omitted)

• Toxicological Research
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• v.16 no.2
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• pp.109-116
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• 2000

The purposes of our study were to optimize the conditions of the screening and testing methods for endocrine disruptors, to characterize these assays using several compounds with well-defined endocrine activity, and to compare the sensitivity between these assays currently undergoing validation. Two in vitro test systems, MCF-7 cells proliferation (E-screen assay) and competitive binding to estrogen receptors (ER) were selected to evaluate the estrogenic effects. 17$\beta$-Estradiol (E2) and diethylstilbestrol (DES) were used as a positive control in vitro test. Also, E2 and ethinyl estradiol (EE) were used as a positive control in vivo uterotrophic assay. In in vitro test, E2 and DES showed a strong estrogenic response at concentration of 1.0 nM. In uterotrophic assay, E2 (0.3 $\mu\textrm{g}$/kg) and EE (0.3 $\mu\textrm{g}$/kg) produced a significant increase in uterus and vagina weight in both immature and ovariectomized rats. Although we did not com-pared the specificity between in vivo and in vitro assays, these assay systems may serve as a good tool for endocrine disruptors screening methods. Our data indicate that these assay systems exhibit some difference in their sensitivity to the same estrogenic compounds. Therefore, as a first rapid screening assay for estrogenic activity qf unknown chemicals, at least two assay systems should probably be carried out with a view of high sensitivity and standardization conditions. Also, a careful validation tests are necessary to obtain a reasonable degree of reproducibility.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.1-8
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• 2022

Objectives : This study aimed to investigate the synergistic effect of combining Cynanchi Wilfordii Radix extract with Humuli Lupuli Flos extract on estrogenic and anti-osteoclastogenic activity. Methods : Estrogenic effect of a mixture of Cynanchi Wilfordii Radix extract and Humuli Lupuli Flos extract (CWHL), Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin (an active ingredient of Cynanchi wilfordii Radix extract) and 8-prenylnaringenin (an active ingredient of Humuli Lupuli Flos extract) were examined by proliferation E-screen assay and expression of estrogen inducible gene, pS2 via Real Time-PCR (RT-PCR) in MCF-7 estrogen responsive cells. And their estrogenic activities were investigated how to modulate Estrogen receptor 𝛽 by binding affinity assay. Inhibitory effect of CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin on RANKL-induced osteoclast differentiation were tested by TRAP (Tartrate-resistant acid phosphatase) staining in osteoclastogenic RAW 264.7 cells. Results : CWHL, Humuli Lupuli Flos extract and 8-prenylnaringenin accelerated the proliferation of MCF-7 and the expression of pS2 in MCF-7. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin bind to estrogen receptor 𝛽. CWHL, Cynanchi Wilfordii Radix extract, Humuli Lupuli Flos extract, caudatin and 8-prenylnaringenin inhibited RANKL-induced osteoclastogenesis in osteoclastogenic RAW 264.7. CWHL is more effective for all markers than Cynanchi Wilfordii Radix extract or Humuli Lupuli Flos extract alone. Conclusions : CWHL may a potential therapeutic agent for menopause and osteoporosis as a natural food resource. CWHL as a natural food source has therapeutic potential in cases of menopause and osteoporosis.

• Journal of Environmental Health Sciences
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• v.33 no.3
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• pp.207-210
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• 2007

The study was designed to determine the estrogenic effect of some penicillins on endocrine function in adult Japanese medaka (Oryzias latipes). Vitellogenin (Vtg) produced in male fish has been used for a biomarker to study endocrine disrupters. $17\beta-estradiol\;(E_2)$ was used a positive control that was induced Vtg in male fish. Result of total protein qantification and ELISA for female and male fish were exposed to $17\beta-estradiol$ 10ng/ml for $3\sim5$ days. As a result, male fish exposed to amoxicillin respectively appeared 0.75, 0.23, 8.21 and $9.36\%_{\circ}$ of 1, 10, 100 and 1000 ppm respectively, that value was elevated compared with control male fish. Male fish exposed to ampicillin respectively appeared 1.85, 4.68, 0.85 and $39.59\%_{\circ}$ of 1, 10, 100 and 1000 ppm respectively, that value was elevated compared with control male fish. This study is one of the first reports suggesting potential endocrine disruption of some penicillins in aquatic ecosystem. These results suggest that vitellogenin and estrogen receptor induction patterns alter in male medaka treated with selected estrogenic compounds, and that these results may be useful molecular biomarkers for screening estrogenic EDCs (endocrine-disrupting chemicals) in the shortest possible time.

• Environmental Analysis Health and Toxicology
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• v.19 no.4
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• pp.375-382
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• 2004

This study was designed to investigate potential endocrine disrupting effects of several industrial wastewater effluents discharged from cosmetic, plaiting, paint, textile industry using EROD bioassay and E-Screen assay. The results of E-screen assay showed that textile industrial wastewater could act as a full agonist and cosmetics and plaiting industrial wastewater could act as a partial agonist. On the contrary, the wastewater discharged from paint industry did not show any estrogenic effect. Estrogenic activity in the effluents of cosmetic and paint industrial wastewater was lower than that in the influents indicating that the wastewater treatment process minimized the effects of discharges on water quality. Despite of these results, it was recognized that wastewater treatment was not always minimize toxic impact. In this study, increased estrogenic effect was observed in the effluents of plating and textile wastewater, and EROD activity was increased in the effluents of cosmetic and plating wastewater.

• Molecular & Cellular Toxicology
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• v.2 no.1
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• pp.15-20
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• 2006

Genistein is a potent, plant-derived isoflavone that displays estrogenic activity at low concentrations but inhibits proliferation at high amounts. However, the molecular mechanism of genistein is not completely understood. In the present study, the biphasic effects (estrogenic and antiestrogenic activity) of genistein on the growth of MCF-7 cells were identified. Genistein within a low range of concentration, $1-10\;{\mu}M$, stimulated proliferation, while $50-100\;{\mu}M$ caused apoptotic cell death. Additionally, genistein at a low concentration induced estrogen receptor (ER)-mediated gene expression and ER phosphorylation. When pre-treated with PD98059, an MEK inhibitor, ER-mediated gene expression and ER phosphorylation by genistein were noticeably increased. However, the increased gene expression and phosphorylation did not enhance cell proliferation. Moreover, it was observed that ER-mediated signaling performs an important role in the MAPK pathway. The proliferation and apoptosis in genistein-treated MCF-7 cells were partially dependent on the Bcl-2 level. The addition of IC1 182, 780, an estrogen receptor antagonist, inhibited Bcl-2 expression induced by genistein. This study suggests that there is a close relationship between Bcl-2 and the ER signaling pathways in MCF-7 cells.

• Toxicological Research
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• v.33 no.1
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• pp.71-77
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• 2017

Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

• Toxicological Research
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• v.31 no.4
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• pp.331-337
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• 2015

Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

• Ecology and Resilient Infrastructure
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• v.6 no.2
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• pp.128-135
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• 2019

This study evaluates the effect of dissolved effluent organic matter (SE-dEfOM) from sewage wastewater treatment plants on the adsorption and estrogenic activity of bisphenol A (BPA). Specific ultraviolet absorbance and fluorescence index analyses indicated that SE-dEfOM was mainly microbially derived non-humic substances differed from Suwannee River natural organic matter (SR-NOM) as reference. Both Langmuir and Freundlich models successfully explained the adsorption of BPA onto both SE-dEfOM and SR-NOM. Additionally, the SE-dEfOM showed higher binding capacities and affinities for BPA than those of SR-NOM, resulting in better reduction of the estrogenic activity of BPA. These findings suggest that the binding and toxicity of BPA are largely dependent on the source of organic matters.