• 한국식품과학회지
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• 제47권5호
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• pp.667-672
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• 2015

저성장 어린이들을 대상으로 하는 성장호르몬 치료는 다양한 부작용과 투여과정의 스트레스로 인한 환자 순응도 감소, 고가의 치료 비용 등의 단점을 가지고 있다. 이러한 이유로 부작용 발생의 위험성이 작고 낮은 비용으로 어린이의 성장에 도움을 줄 수 있는 천연물 유래 기능성 소재 개발에 대한 관심이 증가하고 있다. 그러나 성적으로 미성숙 상태인 어린이를 대상으로 한다는 점, 에스트로겐에 의한 뼈 성장과 성조숙증 발병기전 연관성, 천연물에 존재하는 다양한 식물성 에스트로겐의 영향으로 안전성에 대한 우려가 존재하는 것이 사실이다. 따라서 본 연구에서는 앞선 연구를 통하여 뼈 성장 촉진 효과가 확인된 시험물질의 안전성을 확인하기 위하여 난소를 절제한 실험동물에 시험물질을 4주간 투여한 후 시험물질이 식물성 에스트로겐으로 작용하여 성조숙증과 성장호르몬 이상을 일으킬 가능성을 확인하고자 하였다. 실험 결과 난소 절제로 인한 체중증가, 혈중 지질 농도의 증가, 자궁 벽 두께의 감소 등이 나타남을 확인하였으며 시험물질의 4주 투여가 이러한 변화에 영향을 끼치지 않음을 확인할 수 있었다. 또한 혈중 에스트로겐 농도, 혈중 성장호르몬 농도를 분석한 결과 시험물질 투여가 아무런 영향을 주지 않음을 확인하였다. 이러한 결과는 백수오와 한속단 동량 혼합물이 생체 내에서 식물성 에스트로겐으로 작용하지 않는다는 것을 의미하며 반복투여에 의한 성장호르몬 이상을 일으키지 않는 것으로 판단된다.

• 대한화장품학회지
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• 제40권3호
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• pp.279-287
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• 2014

폐경 이후 여성에서 발생되는 에스트로겐의 감소는 피부노화와 밀접한 관련이 있으며, 피부의 정상적 상태와 기능을 저하시키게 된다. 지난 10여 년간 보고된 많은 연구결과를 살펴보면, 에스트로겐은 폐경 이후 여성의 피부에서 콜라겐 감소를 막아주고, 탄력을 회복시키며, 건조한 피부를 개선시키는 등의 피부 안티에이징 효능을 가지는 것을 알 수 있다. 에스트로겐과 유사한 구조로 인해 파이토에스트로겐이라 알려진 이소플라본은 자외선에 의해 유도된 피부 손상을 보호하는 기작이 널리 알려져 왔으나 피부세포에서 에스트로겐과 유사한 안티에이징 효능을 가지는지에 대해서는 많은 연구가 진행되지 않았다. 이에 본 연구에서는 콩류 등에 많이 함유된 이소플라본인 다이드제인이 에스트로겐과 유사한 활성 및 효능을 가지는지 밝히고자 하였다. 먼저 에스트로겐 수용체와의 결합을 통한 transcriptional activity에 미치는 효과를 luciferase assay를 통해 살펴본 결과, 다이드제인은 대조군에 비해 농도 의존적으로 estrogen receptor-dependent transcriptional activity를 유의하게 증가시켰다. 다음으로 사람의 피부 섬유아세포를 이용하여 다이드제인이 세포외 기질단백질 성분들의 발현에 미치는 효과를 조사한 결과, 다이드제인은 콜라겐 타입 I, 콜라겐 타입 IV, 엘라스틴 및 피브릴린-1의 발현을 유의하게 증가시키는 것을 확인할 수 있었다. 모든 실험조건에서 에스트로겐 단독 효능과의 비교 분석을 통해 다이드제인은 에스트로겐과 유사한 효능을 가진다는 것을 확인할 수 있었다. 본 연구 결과를 통해 다이드제인은 기존에 알려진 이소플라본의 광보호 효능과 더불어 파이토에스트로겐 효능을 가짐으로써 갱년기 여성의 피부 안티에이징을 위해 활용할 수 있을 것이라 제안한다.

• 한국식품과학회지
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• 제37권4호
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• pp.549-556
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• 2005

45종 식용 및 약용식물 에탄을 추출물의 에스트로젠 활성 및 항산화활성을 측정하였고 폴리페놀과 플라보노이드 함량을 측정 비교하였다. 재조합 효모법을 이용하여 에스트로젠 활성을 측정한 결과 감초, 강황, 경포부자, 구아바, 느릅(줄기), 도꾸다미, 백화사설초, 대황, 상백피(중국산), 상황버섯, 석류, 복분자(과육, 씨), 원지, 은행, 초두구, 홍화, 황정이 유의적으로 높은 활성을 나타내었다. 특히, 감초와, 대황은 $100{\mu}g/mL$의 농도에서 1mg/mL 보다 더 높은 활성을 나타내었다. DPPH 라디칼 소거능과 TBARS 생성 억제능 두 가지가 모두 우수한 소재는 감초, 구아바, 느릅, 대황, 복분자, 초두구였다. 총 폴리페놀은 초두구가 594.7mg/g catechin eq.으로 가장 높았으며 삼칠근이 8.6mg/g catechin eq.으로 가장 낮았고, 플라보노이드 함량은 강황이 약 394.9mg/g naringin eq.으로 가장 높았고 황정이 1.7mg/g naringin eq.으로 가장 적었다. 폴리페놀의 함량이 높은 식물의 대부분이 플라보노이드의 함량도 많았다. 시료 추출물의 라디칼 소거 활성과 폴리페놀 함량간에 양의 상관관계를 나타내었으나$(r^2=0.61)$, 지질 과산화 억제능 및 에스트로젠 활성과 폴리페놀 함량 간에는 유의적인 상관성이 적었다. 감초, 대황은 에스트로젠 활성이 높으면서 항산화능이 높았다. 이상의 결과는 파이토에스트로젠 활성을 가진 천연 소재를 선정하는데 기초 자료로 활용될 수 있을 것으로 사료된다.

• Journal of Ginseng Research
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• 제43권4호
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• pp.527-538
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• 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
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• 제15권23호
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• pp.10067-10070
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• 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.

• 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.

• Toxicological Research
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• 제17권1호
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• pp.65-71
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• 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
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• 제20권2호
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• pp.189-195
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• 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
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• 제36권5호
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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)

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.293.2-293.2
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• 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)