• Nutrition Research and Practice
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• v.8 no.5
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• pp.539-543
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• 2014

BACKGROUND/OBJECTIVES: Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause. MATERIALS/METHODS: In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS). RESULTS: Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-${\beta}$ estradiol concentrations in young rats, and 17-${\beta}$ estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans. CONCLUSIONS: Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal women.

• BMB Reports
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• v.38 no.3
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.4
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• pp.163-169
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• 2018

Objective: Zearalenone (ZEA) is a mycotoxin with potent estrogenic effects. Saffron is an herbal product that has antioxidant activities. The objective of this study was to investigate the protective role of saffron against reproductive toxicity induced by ZEA in female mice. Methods: Ninety 8-week-old female mice were randomly allocated into three treatment groups. The first group received an intraperitoneal injection of ZEA (2.5 mg/kg) on alternate days. The second group received ZEA (2.5 mg/kg) on alternate days plus oral saffron daily (50 mg/kg). The third group was treated with a vehicle of 1% dimethyl sulfoxide (DMSO) on alternate days, as a control. Ten mice were euthanized from each group at 30, 60, and 90 days of treatment. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol ($E_2$), and progesterone (P) were assessed. The uterus and ovaries were examined for changes in size or morphology. Results: Serum levels of LH, FSH, $E_2$, and P in the female mice treated with ZEA plus saffron were significantly higher than in those treated with ZEA alone, and were not significantly different from those treated with 1% DMSO. The female mice treated with ZEA alone showed a reduction in size of the uterus and abnormal architecture of the ovaries. Conclusion: The administration of saffron to female mice resulted in a significant reduction in ZEA-induced alterations in reproductive hormone levels, the size of the uterus, and the morphology of the ovaries.

• The Journal of Korean Obstetrics and Gynecology
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• v.36 no.4
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• pp.1-20
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• 2023

Objectives: The object of this study was to observe the complex anti-climacterium potentials of Yuklinzu aqueous extracts (YLZ), using bilateral ovariectomy (OVX) female ddY mice similar to women postmenopausal symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis and hepatic steatosis. Methods: In order to evaluate anti-climacterium effects of YLZ, six groups of mice were used; sham control, OVX control, 17β-estradiol, YLZ 500, 250 and 125 mg/kg treated groups. Since 28 days after bilateral OVX surgery, YLZ were administered orally for 84 days, once a day. And then we evaluated anti-climacterium effects divided into five categories; estrogenic effects, anti-obesity, hypolipidemic effects, hepatoprotective effects and anti-osteoporotic effects. The results of YLZ were compared with 17β-estradiol 0.03 ㎍/head/day subcutaneous treated OVX mice. Results: As a result of OVX, obvious changes related to the estrogen-deficient menopausal symptoms - obesity, hyperlipidemia, hepatic steatosis and osteoporosis were displayed in mice. However, these menopausal symptoms induced by OVX were significantly inhibited by 84 days of consecutive treatment of 17β-estradiol, YLZ 500, 250 and 125 mg/kg, respectively. Especially, YLZ showed obvious dose-dependent inhibitory activities on the OVX-induced climacterium changes in mice, and YLZ 500 mg/kg showed comparable inhibitory effects against menopausal symptoms in comparison with those of 17β-estradiol 0.03 ㎍/head/day subcutaneous treatment. Conclusions: The results suggest that oral administration of YLZ 500, 250 and 125 mg/kg has obvious dose-dependent favorable anti-climacterium effects in OVX mice. Especially, YLZ 500 mg/kg showed comparable inhibitory effects against menopausal symptoms in comparison with those of 17β-estradiol 0.03 ㎍/head/day subcutaneous treatment.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.18-44
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• 2017

Purpose: The object of this study was to observe the anti-climacterium activity of Gagamguibiondam-tang (GGOT) on ovariectomized (OVX) rats, a well-documented rodent models resembles with women postmenopausal climacterium symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis, organ steatosis and mental disorders. Methods: In this study, anti-climacteric effects were evaluated separated into three categories; 1) anti-obese, 2) anti-uterine atrophy and 3) anti-osteoporotic effects. Five groups were used (8 rats in each group); sham control, OVX control, GGOT 500, 250 and 125 mg/kg administered groups. Twenty-eight days after bilateral OVX surgery, GGOT were orally administered, once a day for 84 days, and then the changes on the body weight and gain during experimental periods, serum estradiol levels, abdominal fat pad and uterus weights with histopathology of abdominal fat pads (total thickness and mean adipocyte diameters) and uterus (total, epithelial and mucosal thickness, percentages of uterine gland regions) for anti-obese and estrogenic effects. In addition, femur, tibia and fourth or fifth lumbar vertebrae (L4 or L5) wet, dry and ash weights, mineral density (BMD), bone strength (failure load), serum osteocalcin and bone specific alkaline phosphatase (bALP) contents, histological and histomorphometrical analyses - bone mass and structure with bone resorption, were monitored for anti-osteoporosis activity. Results: As a result of OVX, noticeable increases of body weight and gains, food and water consumption, weights of abdominal fat pad deposited in dorsal abdominal cavity, serum osteocalcin levels were demonstrated in this experiment with decrease of uterus, femur, tibia and L5 weights, serum bALP and estradiol levels. In addition, marked hypertrophic changes of adipocytes located in deposited abdominal fat pads, uterine disused atrophic changes, decreases of bone mass and structures of femur, tibia and L4 were also observed in OVX control rats with dramatic increases of bone resorption markers, the Ocn and OS/BS at histopathological and histomorphometrical analysis in this study as compared with sham-operated control rats, suggesting the estrogen-deficient climacterium symptoms - obese and osteoporosis were induced by OVX, respectively. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by 84 days of continuous oral treatment of GGOT 500, 250 and 125 mg/kg, respectively. Especially, GGOT 500, 250 and 125 mg/kg showed clear dose-dependent inhibitory activities on the OVX-induced climacterium signs. Conclusion: The results suggest that oral administration of GGOT 500, 250 and 125 mg/kg has clear dose-dependent favorable anti-climacterium effects - estrogenic, anti-obese and anti-osteoporotic activities in OVX rats in this experiment.

• Korean Journal of Plant Resources
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• v.30 no.2
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• pp.240-264
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• 2017

The present study was carried out to identify traditional konwledges on Korean Campanulaceae plants and conduct a comprehensive review of them through analyzing phytochemistry and pharmacology of Korean Campanulaceae plants. According to the literature study, the ethnobotanical plants of Korean Campanulacae consisted of a total 18 taxa. Of them, 12 taxa including Platycodon grandiflorus, Adenophora triphylla var. japonica, Codonopsis lanceolata and others have been used as ethnomedicinal plants. These plants have been used for the treatment of 49 diseases such as cold, asthma and postnatal care. Phytochemical studies have identified the constituents present from Korean Campanulaceae (Adenophora, Codonopsis, Platycodon, Campanula and Asyneuma). A wide range of chemical compounds comprised 109 triterpenes, 8 sterols, 4 polyacetylenes, 21 alkaloids, 14 flavonoids, 14 phenolic acids, 11 phenolic glycosides, 8 phenylpropanoids and 22 other compounds. Pharmacological studies of these compounds have demonstrated immuno-stimulating, anti-inflammatory, anti-asthmatic, apophlegmatic and anti-allergic effects. They have also shown antioxidant, estrogenic, anti-diabetic, hepatoprotective, neuroprotective, antinociception and anti-tumor activities, as well as anti-obesity and cardiovascular effects. In light of traditional knowledge and phytochemical and pharmacological studies summarized, uses of Korean Campanulaceae based on traditional knowledge (for the treatment diseases and conditions of respiratory, pregnancy, childbirth, puerperium, genitourinary, circulatory, musculoskeletal and other systems) have been supported by phytochemical and pharmacological studies.

• Journal of Life Science
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• v.18 no.11
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• pp.1578-1583
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• 2008

The purpose of this study was to investigate the effects of sea tangle (ST) extracts on formation of collagen and collagen cross-link in ovariectomized rats. From day 3 until 42 after the ovariectomy, Sprague-Dawley female rats were randomly assigned to the following groups: sham-operated rats(Sham), ovariectomized control rats (OVX-control), ovariectomized rats supplemented with ST at 50 mg/kg bw/day (OVX-ST50), 200 mg/kg bw/day (OVX-ST200). The ethanol extraxcr of ST was orally administrated at 1 ml/day. The change of collagen content was investigated in bone, cartilage and skin of ovariectomized rats. Effects of ST extract on the amount of collagen was examined by measuring the hydroxyproline, which is a specific amino acid existing in collagen. The ovariectomy resulted in a decrease in the levels of collagen content in bone and cartilage tissues. However, the supplementation with the sea tangle extract prevented the decrease in the collagen level in bone and cartilage tissues. Pyridinoline is pyridinium cross-link formed in the mature form of collagen from lysine and hydroxylysine residues. Although the pyridinoline content in bone collagen declined after ovariectomy, it was recovered to a normal level of Sham group by the supplementation with the ST extracts. In addition, the deoxypyridinoline content in bone collagen, which was reduced after ovariectomy was enhanced to normal level by the supplementation with the ST extract. These results was consistent with the conclusions based on estrogenic activities of ST.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.109-109
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• 2002

In recent reports, the multiple reproductive defects such as cryptorchidism, hypospadias, epididymal cysts, low sperm counts, and testicular cancers are increased in humans, and these changes were doubted by the chemicals with estrogenic or antiandrogenic activities in our environment. To compare the effects of neonatal exposure of di (n-butyl) phthalate and flutamide on the development of reproductive organs and to identify the specific mechanisms of these abnormalities related to the male reproducton, Sprague-Dawley neonate male rats were injected subcutaneously during 5-14 days after birth with corn oil (control), flutamide (0.05, 0.1, and 0.5 mg/animal) and DBP (5, 10, and 20 mg/animal). Animals were killed at 31 (immature) and 42 (pubertal) days of age respectively and blood was collected from abdominal aorta for serum testosterone analysis. Testes, epididymides, seminal vesicles, ventral prostate, levator ani plus bulbocavernosus muscle (LABC), cowpers glands and glans penis were weighed. Expression of steroid hormone receptors (AR and ER) was examined in the testes and ventral prostate. At 31 days of age, ventral prostate, seminal vesicles, LABC, and cowpers glands significantly decreased in the flutamide (0.5 mg/animal) and DBP (20 mg/animal), but serum testosterone levels were not changed. Flutamide slightly delayed the testes descent at the high dose (0.5 mg/animal), but DBP did not show any significant effect on the testes descent at all doses. DBP and flutamide decreased the expression of AR protein in the testes but did not affect the expression of ERa and ER protein in the testes. At 42 days of age, ventral prostate, seminal vesicles, and cowpers glands weights were still significantly decreased at the high dose of flutamide (0.5 mg/animal) and DBP (20 mg/animal), but the weights of testes and epididymides were not different. Serum testosterone decreased significantly in DBP treated animals and slightly, not significantly, in flutamide group. While DBP still significantly decreased the expression of AR protein in testis, flutamide recovered from downregulation of AR protein and did not affect the expression of ERa and ER protein in the testes. Based on these results, flutamide and DBP have shown several similar patterns in reproductive abnormalitis, but some marked differences which may be caused by different acting mechanism.

• Biomedical Science Letters
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• v.11 no.2
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• pp.175-183
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• 2005

The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.7
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• pp.1114-1119
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• 2003

The aim of this study was to evaluate the effects of Sedum sarmentosum Bunge (SS) on the collagen content of the connective tissues in ovariectomized rats. From day 2 until day 37 after the ovariectomy, Sprague-Dawley female rats were randomly assigned to the following groups: sham-operated rats (Sham), ovariectomized control rats (OVX-control), ovariectomized rats supplemented with SS at 50 mg/kg BW/day (OVX-SS50), 100 mg/kg bw/day (OVX-SS100) and 200 mg/kg bw/day (OVX-SS200), and an ethyl ether fraction of SS at 10 mg/kg bw/day (OVX-EE) and an ethyl acetate fraction of SS at 10 mg/kg bw/day (OVX-EA). The SS ethanol extracts and SS fractions were orally administrated 1 mL per day. The OVX rats were significantly heavier than the sham-operated rats at all time points, but supplementation with the SS extracts tended to gain weight less than OVX-control. Supplementation with the SS extracts prevented a decrease in the collagen level in bone and cartilage tissues. These results are consistent with the conclusions based on the estrogenic activities of SS. Therefore, it may be used to possibly improve the quality of life in menopausal women.