• Korean Journal of Food Science and Technology
• /
• v.47 no.5
• /
• pp.667-672
• /
• 2015

Cynanchum wilfordii and Phlomis umbrosa Turcz. are known to contain isoflavone, a representative phytoestrogen. This study was performed to determine whether the extract mixture of C. wilfordii and P. umbrosa Turcz. would induce an estrogenic effect in ovariectomized rats. The extracts were administered to the ovariectomized rats at 30, 60, 120 mg/kg per day for 4 weeks, respectively. They showed no estrogenic effect, which was indicated by the decrease in uterus wall thickness as well as the increase in body weight and the level of cholesterol and triglyceride. The extracts also had no effect on the concentrations of estrogen and growth hormone in the serum. However, the increase in alkaline phosphatase activity, which leads to protection against the bone loss caused by ovariectomy, was noted on administration of the extract. Therefore, it seemed that the extracts of C. wilfordii and P. umbrosa Turcz. had no estrogenic effect in rats.

• Journal of the Society of Cosmetic Scientists of Korea
• /
• v.40 no.3
• /
• pp.279-287
• /
• 2014

Estrogen deficiency results in a reduction of skin quality and function in postmenopausal women. Over the past decade, many studies have supported that estrogen provides anti-aging effects as a result of the ability of estrogen to prevent skin collagen decline, restore skin elasticity, and increase skin hydration in postmenopausal women skin. Due to their structural similarity with estrogen, isoflavones have been called phytoestrogens. Photoprotective effects of isoflavones are well established while their estrogenic-like activities are not fully understood in human skin. In this study, we investigated whether daidzein, an effective isoflavone, has phytoestrogenic activity and induces transcriptional change of extracellular matrix components in dermal fibroblasts. We examined the luciferase activity of daidzein and ${\beta}$-estradiol using transiently transfected NIH3T3-ERE cells. The estrogenic receptor-dependent transcriptional activity was increased in a dose-dependent manner when treated with daidzein, with a maximum of 2.5-fold induction at $10{\mu}g/mL$ of daidzein compared with non-treated control. In addition, daidzein significantly in creased the expressions of collagen type I, collagen type IV, elastin, and fibrillin-1 in human dermal fibroblasts. By comparing with the effects of ${\beta}$-estradiol through out all the experiments, we confirmed that daidzein had estrogenic activity and function in fibroblasts. These results suggest that daidzein-based application, having both photoprotective and phytoestrogenic effects, may be a powerful approach for skin anti-aging of postmenopausal women.

• Korean Journal of Food Science and Technology
• /
• v.37 no.4
• /
• pp.549-556
• /
• 2005

Estrogenic and antioxidant activities of ethanol extracts of 45 edible and medicinal plants were evaluated by ${\beta}-galactosidase$ assay, and DPPH radical scavenging assay, and TBARS inhibition rate, respectively. Total polyphenol contents were in the range of 8.6 (Panax notoginseng Buck F.H. Chen.)-594.7 (Amomum globosum Loureiro) mg/g. Direct correlation between the DPPH radical scavenging activity and polyphenol content $(r^2=0.61)$ was established through simple regression analysis, whereas no correlation was observed between TBARS inhibition rate or ${\beta}-galactosidase$ activity and polyphenol content. Among medicinal plants screened, Glycyrrhiza glabra L. and Rheum undulatum L. showed strong antioxidant and estrogenic activities. Results of this study could be used as fundamental data for selecting potential phytoestrogen candidates.

• Journal of Ginseng Research
• /
• v.43 no.4
• /
• pp.527-538
• /
• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10067-10070
• /
• 2015

Background: Unopposed estrogen has a central role in development of endometrial benign, premalignant and malignant lesions. The aim of this study was to evaluate the anti-estrogenic effect of metformin on endometrial histology in comparison with progesterone. Materials and Methods: A total of 43 patients who were referred to our center for abnormal uterine bleeding and had a histologic diagnosis were disordered proliferative endometrium or simple endometrial hyperplasia were included and randomly distributed in two groups treated with metformin (500mg Bid) or megestrol (40mg daily), respectively, for three months. After this period the patients were evaluated by another endometrial biopsy to assess the impact of the two drugs in restoring normal endometrial histology. Results: Our findings revealed that metformin could induce endometrial atrophy in 21 out of 22 patients (95.5%) while this positive response was achieved in only 13 out of 21 patients (61.9%) in the megstrol group. In addition two low grade endometrial carcinomas in the metformin group responded very well. Conclusions: We conclude that metformin could be used as an effective antiestrogenic agent in control of abnormal endometrial proliferative disorders.

• Journal of the East Asian Society of Dietary Life
• /
• v.15 no.3
• /
• pp.315-322
• /
• 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.

• Toxicological Research
• /
• v.17 no.1
• /
• pp.65-71
• /
• 2001

The key targets of endocrine disruptors are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. A yeast-based steroid hormone receptor gene trascription assay was previously developed for the evaluation of chemicals with endocrine modulating activity. The yeast transformants used in this assay contain the human estrogen receptor along with the appropriate steroid response elements upstream of the $\beta$-galactosidase reporter gene. We tried to evaluate several natural and synthetic steroids of their potential to interact directly with the steroid receptor. Some putative endocrine disruptors, including nonylphenol, are weakly estrogenic. But the combined treatment oj these chemicals with di-(2-ethylhexyl)phthalate (DEHP) significantly increased the $\beta$-galactosidase activity in the yeast transformant. These results suggest that we also have to consider the synergistic effects of endocrine disruptors. In this study, we showed that yeast-based bioassay is a valuable tool for screening potential endocrine disruptors and quantitative determination of estrogenicity. And the possibility that the estrogen receptor binds multiple environmental chemicals adds another level of complexity to the interaction between the endocrine disruptors and the human hormone system.

• Biomolecules & Therapeutics
• /
• v.20 no.2
• /
• pp.189-195
• /
• 2012

Epimedii Herba is a traditional medicinal herb used in Korea and China and exerts estrogenic activity. In this study, we investigated the effect of peripubertal administration of Epimedii Herba on pubertal development in female rats using a modified protocol of the rodent 20-day pubertal female assay. Female Sprague-Dawley rats (21 days old after weaning, 10 rats per group) were divided into five groups: saline (Con), ethinyl estradiol (E2), Epimedii Herba ext (Ext), icariin (ICI), and icaritin (ICT), which were administered by oral gavage (E2 by subcutaneous injection) from postnatal day (PND) 21 through PND40. The time to vaginal opening (VO) was shorter for the Epimedii groups, particularly for the ICT group (p<0.05). Treatment with ICI and ICT significantly increased the duration of the estrus cycle (ICI, 2.78 days; ICT, 4.0 days; control, 1.78 days). Ovary weight was reduced by E2 treatment and increased by the Ext, ICI, and ICT treatments while the weight of the uterus and pituitary glands increased significantly only in the E2 and ICT groups. Although Epimedii Herba displayed relatively weak estrogenic activity, its repeated administration could affect pubertal development in female rats.

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

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.293.2-293.2
• /
• 2002

Bisphenol A ［BPA. 2.2-bis(4-hydroxyphenyl)propane］ is reported to have estrogenic activity: however. its influence on cytokine production or immune system function remains unclear. In this study. we investigated the effects of BPA on the production of nitric oxide (NO) and tumor necrosis factor-a (TNF-a), and on the level of inducible nitric oxide synthase (iNOS) and TNF-a gene expression in mouse macrophages. BPA alone did not affect NO or TNF-a production. (omitted)