• Journal of Ginseng Research
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• v.36 no.2
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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.

• Natural Product Sciences
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• v.25 no.1
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• pp.28-33
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• 2019

A popular approach for the study of estrogen receptor ${\alpha}$ inhibition is to investigate the protein-protein interaction between the estrogen receptor (ER) and the coactivator surface. In our study, we investigated phytochemicals from Rubus coreanus that were able to disrupt $ER{\alpha}$ and coactivator interaction with an $ER{\alpha}$ antagonist. The E-screen assay and molecular docking analysis were performed to evaluate the effects of the estrogenic activity of R. coreanus extract and its constituents on the MCF-7 human breast cancer cell line. At $100{\mu}g/mL$, R. coreanus extract significantly stimulated cell proliferation ($574.57{\pm}8.56%$). Sanguiin H6, which was isolated from R. coreanus, demonstrated the strongest affinity for the $ER{\alpha}$ coactivator-binding site in molecular docking analysis, with a binding energy of -250.149. The initial results of the study indicated that sanguiin H6 contributed to the estrogenic activity of R. coreanus through the activation of the $ER{\alpha}$ coactivator-binding site.

• Journal of Nutrition and Health
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• v.36 no.5
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• pp.452-458
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• 2003

Soybean is a rich source of isoflavones such as genistein and daidzein. Soy isoflavones have both weak estrogenic and anti-estrogenic effects and are structurally similar to tamoxifen, an agent that has an effect similar to that of estrogen in terms of reducing postmenopausal bone loss. The purpose of this study was to determine the effects of differences in protein source (casein vs soy) and isoflavone levels (reduced vs higher levels) on selected bone markers and hormones in growing male rats. Thirty weanling Sprague-Dawley young rats were divided into 3 groups: The control group was fed a casein-based diet, the soy concentrate group was fed soy protein with totally reduced isoflavones content (isoflavones 0.07 mg/g protein), and the soy isolate group was fed soy protein with a higher than normal isoflavones content (isoflavones 3.4 mg/g protein). The degree of bone formation was estimated by measuring serum osteocalcin and alkaline phosphoatase (ALP). By determining collagen cross-linkage by immunoassay and correcting with creatinine values, the bone resorption rate was compared. Serum osteocalcin, growth hormone, estrogen and calcitonin were analyzed using radio immunoassay kits. The bone formation marker and ALP activity were differentiated by protein source, showing higher values than casein in feeding either soy isolate or soy concentrate. In this study using growing rats, the differences in isoflavone contents were not a significant factor in either bone formation or bone reaborption markers. Moreover, the soy isolate group had significantly higher levels of growth hormone than the casein group. The findings of this study suggest that growth hormone is partially responsible for its bone-formation effects in young growing rats. Soy protein and the isoflavones in soy protein are beneficial for bone-formation in growing male rats. Therefore, exposure to soy protein and isoflavones early in life may have long-term health benefits in preventing bone diseases such as osteoporosis. Further study to evaluate the mechanism of action of isoflavones on bones is warranted. (Korean J Nutrition 36(5): 452∼458, 2003)

• The Journal of Pediatrics of Korean Medicine
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• v.29 no.2
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• pp.59-77
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• 2015

Objectives Medical plant has a big role in Herbal Medicines, and most medical plant has phytoestrogens. Therefore some estrogenic effects have been reported in a lot of Korean Medicine literature. Phytoestrogens should be used carefully in children. The objective of this study is to identify reported phytoestrogenic effects in Herbal Medicines and to evaluate the characteristics of the phytoestrogens in Herbal Medicines. Methods A literature search was done with using 8 databases with a limit of reports until 12/31/2013. The estrogenic effects were summarized by each individual Korean Medicine. The frequency of the phytoestrogens was also investigated depending on the Korean medical categorization by the treatment effect. Results and Conclusions Phytoestrogenic effects were reported in 89 Herbal Medicines. Phytoestrogens were act bidirectionally, and the effect was fairly weak compared to estrogen. Phytoestrogenic effect was variable on different cells and tissues. The most frequent phytoestrogenic effect was in tonifying and replenishing medicinal, the following orders were heat-clearing, exterior-releasing, and blood-activating and stasis-dispelling medicinal. Phytoestrogens were not reported in dampness-resolving, digestant, orifice-opening, emetic medicinal.

• Environmental Analysis Health and Toxicology
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• v.20 no.1
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• pp.13-21
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• 2005

The purpose of this study was to determine the effects of bisphenol A (BPA), which is known to have estrogenic activity, on the early development of medaka fish (Oryzias latipes). The fertilized eggs of medaka were treated with BPA at different concentrations for 3 weeks. Embryonic growth, deformation, hatching success, and gonadal differentiation were determined to observe the effects of this chemical. Also we tried to measure the estrogenic activity of bisphenol A using ELISA and RT-PCR methods. By using this techniques, we evaluated the induction of vitellogenin, an estrogen-regulated gene from the whole body-homogenates of larvae. At results, a reduced blood circulation was seen in embryos and peritoneal edema and hindrance of yolk-sac absorption were observed in larvae of treated group. However, BPA at the concentrations tested (2～200 ㎍/L) did not have severe adverse effects on the early life-stages. According to the observation of gonadal histology, inter-sex or sex -reversal was not found in all test fish. After the exposure was ended, vitellogenin mRNA and protein levels were measured in larvae and then their levels were found to be increased in treated group with 200㎍/L. These results indicate that BPA can induce the expression of vitellogenin in early life-stages as well as in adult male fish.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2003.10a
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• pp.57-69
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• 2003

It is well known that many pesticides possess hormonal activity, and affect the developments of wildlife and mammals including human. Currently, pyrethroid insecticides are in worldwide use to control in and outdoor pests, providing potential far environmental exposure. Hormonal activities of these pyrethroid insecticides, however, have been little studied, and the developmental effects of them were no reported. Therefore, we firstly examined the potential estrogenic activities of some pyrethroid insecticides (permethrin, cypermethrin, tetramethrin, deltamethrin, sumithrin, fenvalerate and bioallethrin) by immature rat uterotrophic assay, luciferase reporter gene assay and Calbindin-D$\sub$9k/ (CaBP-9k) gene expression assay. Uterine wet weights were increased by permethrin and the permethrin-induced weights were inhibited by ICI 182780 in the uterolrophic assay. On the other hand tetramethrin significantly reduced uterine and vaginal wet weights, and also inhibited the E2-induced weight increases at all doses tested. Cypermethrin and sumithrin had a tendency to increase uterine weights, although not statistically significant. Permethrin and cypermethrin dose-dependently increased the luciferase activity in reporter gene assay. Northern blot analysis showed that permethrin induced CaBP-9k mRNA expression whereas tetramethrin inhibted. Subsequent studies were conducted to investigate the possible developmental effects of four pyrethroid insecricides (permethrin, cypermethrin, sumithrin and teramethrin). Either diethlbestrol (DES) or 17${\beta}$ -estradiol (E2) was used as a reference control in this study. Pyrethroid insecticides were administered to Sprague Dawley rats via subcutaneous injection at 6 to 18 days of gestation or 1 to 5 days after birth. In utero treatment of permethrin (10mg/kg/day) in female rat resulted in significant increases in uterine and ovarian weights while significant decreases in serum E2 concentration, uterine and ovarian ER${\alpha}$ mRNA levels. Sumithrin and permethrin led to acceleration in vaginal opening of female rat, while delay in preputial separation of male after neonatal treatment. Anogenital distances of PND 18 were significantly reduced in sumthrin-treated, and permerhrin-treated male rats after neonatal treatment. All the pyrethroid insecticides tested caused significant increases in uterine weights on PND 18, while significant reductions in the first diestrus phase when neonataly treated. In addition, exposure to pyrethroids in neonatal period led to significant reduction in relative brain weight in female rat on PND 18, but its weight was recovered in diestrus phase. In summary, Our experimental data demonstrate the possibilities of developmental effects of pyrethroid insecticides via estrogenic or antiestrogenic activity.

• Environmental Mutagens and Carcinogens
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• v.22 no.4
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• pp.274-278
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• 2002

Phthalates, suspected endocrine disruptor, are plasticizer and solvent used in industry, and some phthalates are known as potential carcinogen. Most common human exposure to this compounds may occur with contaminated food. It may migrate into food from plastic wrap or may enter food from general environmental contamination, and it has become widespread environmental pollutants, thus leading to a variety of phthalates that possibly threaten the public health. Dibutyl phthalate (DBP) may playa part of cell proliferator, which mediates changes in gene expression and the metabolism of xenobiotics. An understanding of the role of DBP in modulating gene regulation should provide insight regarding mechanisms of DBP induced xenoestrogenic impact. To elucidate the type of genes that are associated with estrogenic activity induced by DBP at the dose (10$^{-8}$ M) appeared proliferating effects, the pattern of gene expression in MCF7 cells was compared between 17$\beta$-estradiol and DBP exposure in the cDNA microarray. From the results, it showed some differences of gene expression patterns between MCF7 cells treated with 17$\beta$-estradiol and DBP, and also DBP shows estrogenic potential with changes in estrogen-related gene expression levels.

• Journal of Korean Society of Water and Wastewater
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• v.20 no.6
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• pp.893-904
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• 2006

To improve sensitivity of biosensor as yeast two-hybrid detection system for estrogenic activity of suspected chemicals, we tested effects of several combinations of the bait and fish components in the two-hybrid system on Saccharomyces cerevisiae inducted a chromosome-integrated lacZ reporter gene that was under the control of CYC1 promoter and the upstream Gal4p-binding element $UAS_{GAL}$. The bait components that were fused with the Gal4p DNA binding domain are full-length human estrogen receptor ${\alpha}$ and its ligand-binding domain. The fish components that were fused with the Gal4p transcriptional activation domain were nuclear receptor-binding domains of co-activators SRC1 and TIF2. We found that the combination of the full-length human estrogen receptor ${\alpha}$ with the nuclear receptor-binding domain of co-activator SRC1 was most effective for the estrogen-dependent induction of reporter activity among the two-hybrid systems so far reported. The relative strength of transcriptional activation by representative natural and xenobiotic chemicals was well correlated with their estrogenic potency that had been reported with other assay systems.

• Journal of Environmental Health Sciences
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• v.29 no.2
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• pp.16-22
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• 2003

BBP (Butyl benzyl phthalate), a widely used plasticizer. can enter the food and environment as consequence of its manufacture, use, and disposal. BBP was found to be developmental and teratogenic or endocrine disrupting chemical in rats. The effects of BBP were investigated in female rats (P) and second generation (F1) via lactations. Sprague-Dawley were given BBP by oral administration at 0, 5, 10, 100, 1000 mg/kg on day 0 to 21 of lactation period. The results were as follows : At maternal findings, there were some significant changes (p<0.05) in relative organ weight, especially liver and uterus weight by BBP administration. In estrous cycle, high treated group was inclined to be proestrus or estrus compared to control group. BBP indues estrous cycle earlier than the control group. At fetal findings, there were some significant changes in relative liver and spleen weight, especially 100, 1000 mg/kg administered groups. The relative weight of ventral prostate was decreased, so it was represent to dose-response tendency. Parent rats (P) were detected monobenzyl phthalate (MBeP) 3.21~5.81 $\mu\textrm{g}$/ml in 100, 1000 mg/kg dose groups. MBeP of male and female fetuses (F1) were detected at the level of 1.21~2.63 $\mu\textrm{g}$/ml of serum. Male serum concentration oi MBeP was higher than the females'. Estrogen receptor $\alpha$ expression by BBP and bisphenol A in uterus and testis of F1 were studied. The ER$\alpha$ expression were increased in F1 male testis and female uterus. F1 male showed distint ER$\alpha$ expression, especially in the combined exposrue. Synergistic ER$\alpha$ expression was found by combined treatment group of BBP and bisphenol A. From the above results, it could be concluded that the effects of dams and F1 by BBP administration during lactation period were estrogenic, and BBP can transfer to F1 via lactation, and make estrogenic at F1 reproductive organs.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2001.05a
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• pp.126-126
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• 2001

Over the last few years, an increased awareness of endocrine disrupting chemicals (EDCs) and their potential to affect wildlife and humans has produced a demand for practical screening methods to identify endocrine activity in a wild range of environmental and industrial chemicals. It is clear that in vivo methods will be required to identify adverse effects produced by these chemicals. (omitted)