• 생명과학회지
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• 제29권9호
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• pp.1023-1026
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• 2019

본 연구에서는 홍삼, 호로파, 민들레, 백수오, 남가새, 녹각상, 토복령, 호로파, 야관문 등의 8개 한약재의 에스트로겐 유사활성을 파악하고자 하였다. 이를 위하여 한약재의 열수- 및 에탄올-추출물을 제조하였고 in vitro 전사 활성 시험법을 이용하여 에스트로겐 유사활성을 검증하였다. 에탄올추출물에서는 홍삼, 백수오, 호로파, 야관문, 민들레가 에스트로겐 유사활성을 나타냈고, 열수출출물에서는 홍삼, 호로파, 백수오가 에스트로겐 유사활성을 나타냈다. 홍삼추출물은 $500{\mu}g/ml$의 농도에서의 활성은 열수추출물과 에탄올추출물 모두 $10^{-8}M$ $17{\beta}$-estradiol의 활성보다 높은 활성을 보였고, 홍삼 에탄올추출물 $50{\mu}g/ml$과 백수오 에탄올추출물 $500{\mu}g/ml$에서의 활성은 $10^{-9}$와 $10^{-8}M$ $17{\beta}$-estradiol에서의 활성 사이의 활성을 보였다. 이 연구를 통해 홍삼, 백수오, 호로파, 민들레 등을 이용한 식물성 여성호르몬 유사물질을 함유하는 기능성소재의 개발에도 기여할 수 있을 것이며 천연물 유래 여성호르몬 유사물질의 대량 탐색 등이 가능할 것이다.

• 한국환경성돌연변이발암원학회지
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• 제24권4호
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• pp.171-179
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• 2004

Cytochrome P4503A4(CYP3A4) is the most abundnat CYPs in human liver, comparising approximately 30% of the total liver CYPs contents ans is involbed in the metabolism of more than 60% of currently used therapeutic drugs. The expression of CYP3A4 is induced by a variety of structurally unrelated xonobiotics including the antibiotic rifampicin and endogenous hormones, and might be mediated through steroid and xenobiotic receptor(SXR) system. The molecular mechanisms underlying regulation of CYP3A4 gene expression hae not been understood. In order to gain the insight of the molecular mechanism of CYP3A4 gene expression, study has been undertaken to investigate if the histone deacelylation is involved in the regulation of CYP3A4 gene expression by proximal promoter or not. Also SXR was investigated to see if they were involved in the regulation of CYP3A4 proximal promoter activity. HepG2 or Hena-I cells were transfected with a plasmid containing~1kb of the CYP3A4 proximal promoter region (-863 to +64bp) cloned in front of a reporter gene, luciferase, in the presence or absence of SXR or hER. Transfected cells were treated with CYP3A4 inducers such as rifampicin, PCN and RU 486, or with estradiol, in order to exmine to regulation of CYP3A4 gene expression in the presence or absence of trichostatin A (TSA). In HepG2 cells, CYP3A4 inducers and estradiol increased significantly the luciferase activity by CYP3A4 proximal promoter, only when TSA was co-treated after SXR cotransfection. In the case of Hepa-I cells CYP3A4 inducers and estradiol incressed modestly the luciferase activity when TSA was co-treated, but this increment was not enhanced by SXR cotransfection in contrast to HepG2 cells. Taken together, these results indicated that the inhibition of histone deacetylation was required to SXR-mediated increase in CYP3A4 proximal promoter region when rifampicin, or PCN was treated. Futher a trans-activation by SXR may demand other species-specific transcription factors.

• 동아시아식생활학회지
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• 제14권3호
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• pp.233-242
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• 2004

The purpose of this study was to investigated the possibility of Meles meles as an edible functional resource. To assess the effects of Meles meles fermented liquid(ML) with medicinal plants in postmenopausal women, the menopause symptoms, hematological and serum chemical variables and bone health indices were examined. Twenty five postmenopausal women participated in the study. As a result, in postmenopausal women, ML supplements were effective in reducing the incidence of menopause symptoms, such as insomnia(44.0%), sensitivity(40.0%), headache(34.0%), hot flush and decreased vaginal lubrication(20.0%) after 12 weeks. Also serum estradiol and calcitonin and calcium levels were 23.27 pg/mL, 14.88 pg/mL and 8.86 mg/dL before the ML intake. Levels were significantly increased of estradiol and calcitonin and calcium after ML intake during 12 weeks to 30.36 pg/mL, 21.61 pg/mL and 10.01 mg/dL. Osteocalcin and bone alkaline phosphatase activity were 14.36 ng/mL, 21.55 U/L before the ML intake, but according to ML intake, the levels were significantly decreased. In conclusion, ML play benefical roles in the prevention of bone loss and menopause symptoms. Howere current data are not sufficient to determine the effective doses for benefical effect as well as harmful effect and support dietary recommendation level for ML. Therefore, our results should be viewed with caution. But Meles meles fermented liquid with medicinal plants can be used as possible food resources and functional food materials, more studies are needed to identify the proper mechanism of ML.

• 한국임상수의학회지
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• 제27권6호
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• pp.693-697
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• 2010

본 연구는 총 4두의 삵에서 발정기와 비발정기, 임신기와 비임신기 동안의 분변에서 steroid metabolic materials를 추출한 후, TR-FIA kit를 이용하여 estradiol과 progesterone의 농도를 측정하였다. 발정기간 (2월) 중 estradiol 농도의 최저는 평균 $4.02{\pm}1.9$ng/g 이었고, 최고는 평균 $86.01{\pm}35.2$ng/g (dry fecal weight) 이었다. 비발정기(11월)의 최저는 평균 $4.42{\pm}1.32$ng/g 이었고, 최고는 평균 $15.62{\pm}6.84$ng/g 이었다. 임신기 (3월) 중 progesterone농도의 최저는 평균 $427{\pm}24.49$ng/g 었고, 최고는 평균 $1490{\pm}265.27$ng/g 이었다. 비임신기 (11월)의 progesterone의 최저는 평균 $71.25{\pm}29.61$ng/g 이었고, 최고는 평균 $291.75{\pm}90.30$ng/g 이었다. 위의 결과에 따라 삵에서 TR-FIA에 의한 분변내 steroid hormone 의 측정은 발정과 임신에 관련된 난소활동을 비 침습적으로 평가하기 위한 적절한 방법으로 판단되었다. 본 연구는 삵과 같이 접근이 어렵고 멸종위기에 처한 야생동물의 사육관리의 효율화와 번식계획의 수립에 도움이 될 것이다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.202-202
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• 2001

Stable MCF-7-ERE cells, in which pERE-Luc reporter gene has been stably integrated into the genome of the MCF-7 cells, were used to detect the estrogenic activity of various dietary flavonoids.in either pure chemical or mixtures. Estradiol (E2) induced luciferase activity in dose dependent manner and this activity was inhibited by tamoxifen (Tam) concomitant treatment.(omitted)

• 한국발생생물학회지:발생과생식
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• 제22권2호
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• pp.155-163
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• 2018

This study aimed to investigate changes in the activity and mRNA expression of plasminogen activators (PAs) induced by $17{\beta}$-estradiol ($E_2$), human chorionic gonadotropin (hCG), and interleukin-$1{\beta}$ ($IL-1{\beta}$) in porcine endometrial cells. Endometrial cells were isolated from the epithelium and cultured to 80% confluence. They were then treated for 24 h with $E_2$ (0.2, 2, 20, and 200 ng/mL), $IL-1{\beta}$ (0.1, 1, 10, and 100 ng/mL), and hCG (0.5, 1, 1.5 and 2 IU/mL). mRNA expressions of urokinase-type (uPA) and tissue-type (tPA) PAs were analyzed using reverse transcription PCR, and activities were measured using a PA activity assay. mRNA expressions of uPA and tPA increased with $E_2$ treatment; however, this was not significant. Similarly, treatment with hCG did not influence the mRNA expressions of PAs. Interestingly, treatment with 0.1 ng/mL $IL-1{\beta}$ significantly reduced the mRNA expression of uPA, but did not affect that of tPA. Treatment with 2, 20, and 200 ng/mL $E_2$ increased PA activity compared with the control group; treatment with 0.1 and 1 ng/mL $IL-1{\beta}$ significantly increased PA activity compared with the other $IL-1{\beta}$ treatment groups, whereas treatment with 10 and 100 ng/mL $IL-1{\beta}$ decreased. Treatment with 2 IU/mL hCG increased PA activity compared with the other treatment groups, although there were no significant differences between the hCG and control groups. In conclusion, the activity and mRNA expression of PAs were differently regulated by the hormone/cytokine and its concentration in porcine endometrial cells. Therefore, understanding PA regulatory mechanisms may help to improve the reproductive potential of domestic animals.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제22권2호
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• pp.155-163
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• 2000

Osteoporosis is the consequence of an imbalance between osteoclastic and osteoblastic activity, coupled with an increased rate of bone turnover observed with menopause. Estrogen is generally considered to maintain bone mass through suppression of bone resorption. The purpose of this study was to evaluate the rat femoral trabecular change not only in the deficiency of estrogen but also in the administration of estrogen following ovariectomy(OVX). 30 female Sprague-Dawley rats were subjected to bilateral OVX or sham surgery(control). Groups of OVX were divided into 4 groups. The first group was injected daily with vehicle alone for 20 days after 20 weeks following OVX. The additional groups of OVX was injected daily with low, medium, or high doses of $17{\beta}-estradiol$(10, 25 or $50{\mu}g/kg$ BW, respectively). All rats were sacrified 23 weeks after OVX, and their femur were processed for H&E, MT stain and histomorphometry. The results were as follows; 1. In the histomorphometric analysis, the trabecular bone volume/tissue volume, trabecular thickness and trabecular seperation were respectively $31.2{\pm}8.3%$, $54.3{\pm}4.8{\mu}m$ and $280.7{\pm}16.4{\mu}m$ in vehicle treated OVX group and $48.6{\pm}7.3%$, $90.4{\pm}4.5{\mu}m$ and $126.3{\pm}5{\mu}m$ in sham operation group, and they showed statistical significance compare to control group. 2. The trabecular bone volume/tissue volume, trabecular thickness and trabecular separation were respectively $44.4{\pm}4.3%$, $109.5{\pm}12.3{\mu}m$ and $94.9{\pm}8.5{\mu}m$ in low doses of $17{\beta}-estradiol$ injected group and they showed statistical significance compare to OVX group. 3. The trabecular bone volume/tissue volume, trabecular thickness and trabecular separation were respectively $44.4{\pm}4.3%$, $109.5{\pm}12.3{\mu}m$ and $94.9{\pm}8.5{\mu}m$ in medium doses of $17{\beta}-estradiol$ injected group and they showed statistical significance compare to OVX group, but they didn't show statistical significance compare to low doses of $17{\beta}-estradiol$ injected group. 4. The trabecular bone volume/tissue volume, trabecular thickness and trabecular separation were respectively $46.4{\pm}4.5%$, $154.4{\pm}13.2{\mu}m$ and $113.7{\pm}12.8{\mu}m$ in high doses of $17{\beta}-estradiol$ injected group and they also showed statistical significance compare to OVX group, but they didn't show statistical significance compare to other experimental groups. From the above results, metaphyseal bone formation was markedly reduced in OVX rate but treatment of OVX rats with $17{\beta}-estradiol$ resulted in normalization of femur trabecular bone volume. But they didn't show statistical significance the effect of bone formation according to the dose dependency.

• 대한약리학회지
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• 제26권2호
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• pp.167-176
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• 1990

비스테로이드성 항에스트로젠제는 표적기관에서 estrogen 수용체와 상경적으로 결합하므로써 estrogen의 작용을 억제하는 것으로 알려져 있다. 비스테로이드성 항에스트로젠제는 대체로 triphenylethylene계로서 tamoxifen, clomiphene, LYl17018등이 있으며 표적기관에서 estrogen의 작용을 억제하기 때문에 estrogen과 관련된 질환을 치료하는데 이용되어 오고 있다. 본 연구에서는 생후 21-23일된 미성숙 흰쥐를 재료로 항에스트로젠제중 tamoxifen과 LY117018이 자궁세포 성장에 어떠한 영향을 미치며 어떠한 기전으로 estrogen의 작용을 길항하는지를 규명하고자, 항에스트로젠제가 estrogen작용의 중요 지포에 미치는 영향을 비교 관찰하여 다음과 같은 결과를 얻었다. Tamoxifen과 LY117018은 자궁세포에서 estrogen의 영향이 없는 경우에는 estrogen agonist로, estrogen작용하에서는 estrogen antagonist로서 작용하였다. Estrogen 작용의 여러 가지 지표에 대해 tamoxifen이 LY117018보다 agonistic effect는 더 컸으나, antagonistic effect는 LY117018이 더 큰 것으로 나타났다. Estrogen 수용체에 대한 결합능은 LY117018이 estradiol보다는 약간 낮았으나 용량에 비례하여 estrogen 수용체와 결합하였다. 그러나 tamoxifen은 estrogen 수용체에 대한 결합이 아주 낮았다. Estrogen 수용체에 대한 binding affinity는 estradiol(100%), LY117018(77%), tamoxifen(6.3%) 순으로 나타났다. 항에스트로젠제의 생체내 투여는 estrogen 존재 유무에 따라 estrogen 수용체 농도에 agonist 또는 antagonist로 작용하였다. 항에스트로젠제의 단독투여는 progesterone 수용체 생성을 증가시키나, estrogen에 의하여 유도된 progesterone 수용체 생성을 억제하였다. 이상의 결과로 보아, tamoxifen과 LY117018은 estrogen유무에 따라 흰쥐 자궁세포에서 estrogen antagonist로서 뿐만 아니라 agonist로서도 작용함을 알 수 있다. 그러나 estrogen수용체와의 결합능력이 아주 낮은 tamoxifen은, 용량에 비례하여 estrogen수용체에 결합하므로써 작용하는 LY117018과는 다른 기전으로 작용하는 것으로 생각된다.

• Archives of Pharmacal Research
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• 제26권9호
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• pp.756-762
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• 2003

In the current study, our research focused on the estrogenic activity of isoflavonoids, mainly genistein, biochanin A and daidzein. Genistein enhanced the reporter gene expression of MCF-7-ERE-Luc cells, at a concentration as low as 10 nM, with a concentration of 100 nM the achieved gene expression effects were similar to those of 10 pM 17$\beta$-estradiol. Based on the estrogenic activities of biochanin A and daidzein, hydroxyl groups at the 4 and 5 positions are needed for the maximal effect of the genistein. The estrogenic effects of these isoflavonoids were inhibited by the concomitant treatment with tamoxifen. The data showed that the estrogenic effects of isoflavonoids were mediated through estrogen receptors. When the isoflavonoids were tested as mixtures, the estrogenic effects were lower than the arithmetic sum of those induced by each individual isoflavonoid. The estrogenic potency of each isoflavonoid was presented at EC50 levels with a 17$\beta$-estradiol equivalent concentration (EEQ) based on the dose response of each chemical. The EC50s and EEQs of genistein, biochanin A and daidzein were 4.15, 0.89 and 0.18 $\mu$M, and 15.0, 5.12 and 1.83 $\mu$ M/M, respectively. Our data clearly demonstrated that the pERE-luciferase reporter gene assay was suited for the sensitive and quantitative measurement, and large scale screening, of the estrogenicity of chemicals in vitro.

• 한국식품과학회지
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• 제38권2호
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• pp.279-283
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• 2006

홍화씨의 폴리페놀 성분들이 HMGR 활성, LDL-oxidation과 Hep3B 세포로부터의 Apo A1 분비능에 미치는 영향을 조사하였다. 홍화씨 성분은 matairesinol(lignan), acacetin(flavone) 및 N-feruloylserotonin과 matairesinol의 대사산물인 enterolactone을 사용하였다. 그 결과, HMCR 저해활성은 mevastatin이 53%로 가장 높은 활성을 나타내었고 다음은 홍화씨 serotronin 유도체인 N-feruloylserotonin이 45%의 저해활성을 보여 홍화씨 폴리페놀 중에서는 가장 높은 활성을 보였으며 genistein은 35%의 활성을 보인 반면 나머지는 활성이 거의 미미하였다. N-feruloylserotonin의 활성은 용량 의존적 반응을 나타내었다. LDL 산화 억제효과는 사용한 모든 홍화씨 폴리페놀성분에서 나타났는데, 특히 N-feruloylserotonin에서 가장 강한 활성을 보였고 역시 용량 의존적 반응을 보였다. Hep3B에서의 Apo A1 분비능은 mevastatin에서 가장 높았고 enterolactone, genistein 및 ${\beta}-estradiol$에서 분비 증강활성을 나타내었다. 이상의 결과들로 미루어 볼 때, 홍화씨 폴리페놀 성분들은 콜레스테를 생합성과 LDL의 산화를 억제시킴으로서 지질대사 및 동맥경화 개선에 기여할 수 있을 것으로 사료된다.