• Archives of Pharmacal Research
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• 제29권5호
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• pp.354-362
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• 2006

Dietary flavonoids have attracted a great deal of attention as agents for preventing estrogen-related diseases, such as postmenopausal symptoms, and for reducing the risk of estrogen-dependent cancer. Kaempferol is one of the most commonly found dietary phytoestrogen. The aim of this study was to investigate the estrogenic and/or antiestrogenic effect of kaempferol, which can confirm its potency as a preventive agent against estrogen-related diseases. Kaempferol has both estrogenic and antiestrogenic activity, which are biphasic response on estrogen receptor. The estrogenic activity of kaempferol induced via ER-mediated pathway depending on $E_2$ concentration $(\leq\;10^{-12}M)$. Kaempferol $(10^{-5}\;M)$ also caused antiproliferative effect on MCF-7 cell in the presence of $E_2\;(10^{-11}\;M)$ and restored to the addition of excess $E_2\;(10^{-7}\;M)$, which confirms that antiproliferation of kaempferol was induced via ER-dependent pathway. However, at $10^{-4}\;M$, concentration higher than the concentrations at which the estrogenic effects of kaempferol are detected $(10^{-5}\;M)$, kaempferol induced strong antiproliferative effect, but were unaffected by the addition of excess $E_2\;(10^{-7}\;M)$ indicating that kaempferol exerts antiproliferation via ER-independent pathway. In particular, kaempferol blocked the focus formation induced by $E_2$, which confirms that kaempferol might inhibit the malignant transformation caused by estrogens. Therefore, we suggested that kaempferol might regulate a suitable level of estrogenic activity in the body and is expected to have potential beneficial effects in preventing estrogen imbalance diseases (breast cancer, osteoporosis, cardiovascular disease and etc.).

• 생약학회지
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• 제37권1호통권144호
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• pp.21-27
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• 2006

Yeast based estrogenicity assay is the simplest and useful for the assay and the discovery of novel estrogenic substances in natural specimens, The estrogen receptor(ER) modulation activity of 50% EtOH extracts of 101 traditional medicinal herbs was assessed using a recombinant yeast assay system with both a human estrogen receptor expression plasmid and a receptor plasmid. Among them, 14 species proved to be active. Pureariae Flos (flower of Puerraria thunbergiana BENTH.) had the highest estrogenic relative potency$(7.75{\times}10^{-3})$ $(EC_{50}=9.39\;{\mu}g/ml)$. The $EC_{50}$ value of $17{\beta}-estradiol$ used as the positive control was $0.073\;{\mu}g/ml)$ (Relative Potency=1.00). There results demonstrated that some of the traditional medical herb may be useful in the therapy of estrogen replacement.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2005년도 춘계 국제심포지엄 및 학술대회
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• pp.193-193
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• 2005

• 한국환경성돌연변이발암원학회지
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• 제22권3호
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• pp.175-182
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• 2002

Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor $\alpha$ or $\beta$, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4$_{UAS}$). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hER$\beta$ LBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.s.

• 동아시아식생활학회지
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• 제15권3호
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• pp.315-322
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• 2005

In this study we report on the estrogen activity of silkworm pupa and herb extracts in vitro. The estrogenic activity of these resources was investigated by competition binding assays with estrogen receptor $\alpha(ER{\alpha})\;or\;ER{\beta}$, and viability of MCF-7 cells, a human breast cancer cell line. Saturation ligand-binding analysis of $ER{\alpha}\;and\;ER{\beta}$ revealed that all plant extracts competed with estrogen ligand for binding to both ER subtypes with a similar preference and degree and competed stronger with ligand for binding to $ER{\beta}\;than\;to\;ER{\alpha}$. The highest $ER{\alpha}-binding$ sample was silkworm pupa aqueous extract The highest $ER{\beta}-binding$ sample was silkworm pupa oil. These samples were further tested for bioactivity based on their ability to regulate cell growth rate in ER(+) breast cancer cell line, MCF-7 cells. Our studies showed that silkworm pupa, soritae, sesame, yam, pueraria, malt, ginseng, Polygonum multiflorum, and Curcuma longa significantly stimulated the growth of MCF-7 cells (P<0.05). In summary, these results suggested that silkworm pupa and herbs might be useful as potential phytoestrogens.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.195-195
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• 2003

It is well known that diesel exhaust particulate matter contains mutagenic PAHs, such as benzo[${\alpha}$]pyrene, benz[${\alpha}$]anthracene, chrysene, etc. Therefore it is suspected that these chemicals act on estrogen receptor and reveal endocrine-disrupting effects. Recent attention has focused on causative chemicals of endocrine-disrupting effects. We examined the estrogenic activity of respirable diesel exhaust particulate matter derived from diesel powered vehicle. PM2.5 diesel exhaust of vehicle was collected using a high volume sampler equipped with a cascade impactor. Diesel exhaust samples were fractionated according to EPA methods. The presence of estrogenic and antiestrogenic chemicals in PM 2.5 diesel exhaust was determined using E-screen assay. To quantitatively assess the estrogenic and antiestrogenic activities in diesel exhaust particulate matter, estradiol equivalent concentration (bio-EEQ) was calculated by comparing the concentration response curve of the sample with those of the estrogen calibration curve. Weak estrogenic activities and strong antiestrogenic activities were detected in the crude extract and moderately polar fractions. Higher antiestrogenic potency was observed with higher EROD activities in aliphatic and aromatic compounds fraction. In conclusion, estrogenic/antiestrogenic-like activities were present in diesel exhaust particulate matter. However, the health consequences of this observation was unknown, the presence of these activities may contribute to and exacerbate adverse health effect evoked by diesel exhaust particulate matter.

• Journal of Ginseng Research
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• 제36권2호
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• pp.169-175
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• 2012

Ginseng has been used as a traditional medicine for treatment of many diseases and for general health maintenance in people of all ages. Ginseng is also used to ameliorate menopausal systems. We investigated the estrogenic activity of Korean red ginseng (KRG) in a transient transfection system, using estrogen receptor (ER) and estrogen-responsive luciferase plasmids in MCF-7 cells. The extract activated both ER${\alpha}$ and ER${\beta}$. KRG modulated the mRNA levels of estrogen-responsive genes such as pS2 and ESR1 and decreased the protein level of ER${\alpha}$. In order to examine in vivo estrogenic activity of KRG, sixteen female Sprague-Dawley rats separated into four groups were studied for nine weeks: non-ovariectomized (OVX) rats treated with olive oil, OVX rats treated with olive oil, OVX rats treated with 17-${\beta}$-estradiol (E2) in olive oil, and OVX rats treated with KRG extract in olive oil. The experiments were repeated for three times and the data of twelve rats were combined. Body weight of OVX rats was greater than that of sham-operated control rats and was decreased by E2 treatment. Uterine weight increased after E2 treatment compared to OVX rats. However, no difference in body or uterine weight was observed with KRG intake. KRG induced reductions in total cholesterol, low density lipoprotein cholesterol/total cholesterol, high density lipoprotein cholesterol/total cholesterol, and low density lipoprotein cholesterol/high density lipoprotein cholesterol, but not to the same degree as did E2 intake. These results show that KRG does contain estrogenic activity as manifested by in vitro study but the activity is not strong enough to elicit physiological responses.

• 한국발생생물학회지:발생과생식
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• 제11권3호
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• pp.179-185
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• 2007

Estrogen과 estrogenic endocrine disrupting chemicals(EDCs)는 주로 스테로이드 수용체와 작용하여 다양한 표적 단백질 유전자의 전사를 조절한다. 구조적으로 estrogen 수용체와 유사한 estrogen 수용체형 수용체(estrogen receptorrelated receptor, ERR)는 포유동물에서 배발생 후기에 외배엽 형성과 관련되어 있다고 알려진 고아핵수용체(orphan nuclear receptor)이다. 본 연구에서는 해양무척추동물인 둥근성게(Strongylocentrotus nudus)의 발생배를 재료로 estradiol-$17{\beta}(E_2)$과 EDCs의 일종인 nonylphenol(NP)이 발생과정의 형태학적 변화와 $ERR{\beta}$ like 1의 mRNA발현에 미치는 영향을 조사하였다. $E_2$와 NP가 처리된 발생배는 발생속도가 지연되었으며, 초기 유생기에 가까운 후기배의 비정상적인 발달형태가 관찰되었다. 수정란부터 초기 유생기까지 측정한 결과, 이들 화학물질에 의해 $ERR{\beta}$ like 1 mRNA는 포배기에 급격히 감소하는 패턴을 보였다. 이상의 결과는 둥근성게의 초기 배가 $E_2$와 NP에 의해 비정상적으로 발생되며, $ERR{\beta}$ like 1의 감소가 이 비정상적 배발생과 관련되어 있음을 시사한다.

• Journal of Nutrition and Health
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• 제34권8호
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• pp.905-911
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• 2001

Phytoestrogens, especially soy-derived isoflavones, are receiving great scrutiny as a food supplement for preventing hormone dependent diseases such as cardiovascular diseases, cancer, and osteoporosis. These beneficial effects of phytoestrogens are caused by functioning as partial agonists or antagonists of estrogens. In contrast to the common usage of soy bean, Yak-kong(Rhynchosia Molubilis ; ) has been used as supplements of estrogen fir preventing postmenopausal osteoporosis in Oriental medicine. To investigate estrogenic effects of Yak-kong and soy bean on the proliferation of MG-63 osteoblastic cells, each bean was extracted with 70% methanol and dried by freeze-drying. Yak-kong treatment of MG-63 cells resulted in an increase of cell proliferation to a maximum of 76% compared to 68% of soy bean treatment. Treatment of MG-63 cells with Yak-kong extract also resulted in an increase of transactivation of an ERE(estrogen response element)-luciferase reporter plasmid and IGF-I expression selectively. Despite increased effects of both bean treatments on the expression of estrogen receptor $\alpha$(ER$\alpha$) and $\beta$(ER$\beta$), soy bean treatment decreased transactivation of an ERE-luciferase reporter plasmid and did not further enhance IGF-I expression. Together, our data demonstrates that the greater estrogenic response of Yak-kong extract for MG-63 cell proliferation is mediated by ER derived transactivation of ERE and selective induction of IGF-I expression.

• 한국환경보건학회지
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• 제33권3호
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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.