• Biomedical Science Letters
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• v.15 no.3
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• pp.217-227
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• 2009

The present study was set to evaluate the effect of pomegranate extracts on improvement of the menopausal syndromes such as face flushing in ovariectomized rats by carrying out short- and long-term experiments. Pomegranate extracts used to feed rats were prepared from the pulp part which does not contain the rid of the pomegranate, and were dissolved in propylene glycol. From the short-term (16 days) experiment, it was clear that when the 25, 250, 1,250 mg/kg/day concentrations of pomegranate extracts were orally fed to ovariectomized rats, the body temperature of the rats in all the 3 groups were decreased with statistical significance compared to other control groups which were fed with propylene glycol only. Especially, the body temperature decreased by $2.7^{\circ}C$ compared to control groups even when the pomegranate extracts were fed at the low concentration of 25 mg/kg/day implying the usefulness of pomegranate extracts in improving face flushing troubles. In addition, the body weight of the groups fed with pomegranate extracts also decreased when compared to groups fed with only propylene glycol, and the results were also statistically significant. In case of the estradiol level in the blood of rats, the levels were somewhat higher in the groups fed with pomegranate extracts than the control groups, even though the difference was not statistically significant. As found from the results of the short-term experiment, in long-term experiment, the groups fed with pomegranate extracts showed statistically significant decrease in the body temperature and the body weight, whereas the increase of the estradiol levels in blood in each groups were statistically insignificant. During the short- and long-term experiments, no sign of toxicity was found in rats fed with pomegranate extracts indicating no toxic side effects of the pomegranate extracts when orally fed. The concentrations of pomegranate extracts 25, 250, 1250 mg/kg/day treated to ovariectomized rats in this study can be estimated to be 1.5, 15, and 75 g/day when treated to women whose body weight is 60 kg which is average for women with menopausal syndromes. Since even the 75 g/day of high concentration of pomegranate extracts did not show any toxicity in short- and long-term experiments, taking 1.5 g/day concentration of pomegranate extracts would be safe dose for not causing any side effects. Therefore, it can be concluded from the results of this study that taking 1.5 g/day of pomegranate extracts for certain period time will improve the menopausal syndromes including face flushing.

• Journal of Life Science
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• v.33 no.3
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• pp.252-259
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• 2023

A decrease in ovarian function and sex hormone production with aging results in hormone deficiency, which causes menopause in women. Natural products have been investigated to develop estrogen-like substances to improve menopausal status in women. This study was performed to evaluate the efficacy of Gastrodia elata Blume extract (TVB-1000) in ovariectomized rats. After a recovery period of 7 days, the TVB-1000 treatment group was orally administered at 16, 40, and 100 mg/kg for 12 weeks. In the OVX-positive control group, 17β-estradiol was injected subcutaneously into the dorsal region of rats at a dose of 10 ㎍/kg. Results show that TG and LDL-C, which are cardiovascular disease markers, were significantly decreased in all concentrations of TVB-1000 administration in the treatment group, and the LDL-C/HDL-C ratio significantly decreased in the medium and high TVB-1000 concentrations of the treatment group. In addition, in the high concentration TVB-1000 treatment group, the weight of abdominal fat decreased with statistical significance. The low-dose and medium-dose administration groups showed statistical significance and the expression level of their ER-α increased, but ER-β did not show a significant change. The above experiment shows that owing to the estrogen-like effect of TVB-1000, it can be useful as a functional food material to prevent cardiovascular disease, which is one of the menopausal symptoms.

• Journal of Nutrition and Health
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• v.37 no.9
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• pp.786-793
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• 2004

Women with menopause or rats with ovariectomy is associated with increased body weight, body fat and insulin resistance, which are components of metabolic syndrome. Increased prevalence of metabolic syndrome after menopause might be associated with mitochondrial dysfunction, since mitochondrial oxidative and phosphorylation activity is strongly correlated with insulin sensitivity. Although estradiol replacement prevents the metabolic syndrome, harmful effect of estradiol hampers the casual usage to prevent the metabolic syndrome. It has been reported that genistein has a mild estrogenic activity, decreases fat mass in mice and has an antidiabetic role in diabetic rats. Although insulin resistance is closely related to mitochondrial functions, there has not been yet any study in regard to the effect of dietary genistein on mitochondrial function in the insulin resistant female subjects induced by ovariectomy or similar situation. The present study investigated whether the supplementation of genistein in the high fat diet affected the mitochondrial function of high fat fed ovariectomized rats. Female Sprague Dawley rats (8 weeks old) were assigned to the following groups: sham-operated+ high fat diet (S, n=6); sham-operated + high fat diet with 0.1% genistein (S + G, n=7); ovariectomized + high fat diet (OVX, n=8); ovariectomized + high fat diet with 0.1% genistein (OVX+ G, n=8). Ovariectomy significantly increased body weight compared with S group. Genistein consumption in ovariectomized (OVX + G) rats decreased body weight gain compared with OVX rats. Liver weights were increased by ovariectomy. The hepatic mitochondrial protein density expressed as mg per g liver was lower in the OVX group than in the S group. However, OVX + G group showed the increased mitochondrial protein density similar to the level of S group. When mRNA levels of genes related to mitochondria such as peroxisome proliferator-activated receptor ${\gamma}$ coactivator 1 (PGC-1) and cytochrome c oxidase subunit III (COX III) were measured, there were decreases in the mRNA levels of PGC-1 and COX III in S + G, OVX and OVX + G group. The activity of cytochrome c oxidase was not different between groups. We could observe the decrease in succinate dehydrogenase (SDH) activity per g liver in OVX rats. Genistein supplement increased SDH activity. In conclusion, genistein supplementation to the OVX rats enhanced mitochondrial function by increasing mitochondrial protein density and SDH activity. The improvement in mitochondrial function by genistein can contribute to the improvement in metabolic syndrome.

• Korean Journal of Food Science and Technology
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• v.48 no.6
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• pp.604-609
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• 2016

In postmenopausal women, estrogen deficiency can be associated with metabolic diseases, such as obesity, diabetes, and cardiovascular diseases. The purpose of this study was to investigate factors related to lipid, glucose and antioxidnat metabolism. Sprague-Dawley female rats were subjected to either bilateral ovariectomy or sham operation and randomly divided into 3 dietary groups, (n=8) sham-operated fed with normal diet (SHAM), ovariectomized fed with normal diet (OVX), and ovariectomized fed with normal diet supplemented with Eucommia ulmoides extract (OVX-EU). The OVX-EU group showed significantly lower body weight, triacylglycerol, and total cholesterol than that showed by the OVX group. In addition, the OVX-EU group showed improved lipogenesis, glucose-regulating enzyme activities, adipokine and antioxidant enzyme activities. These findings demonstrate that extracts from E. ulmoides extract can be used as a functional food.

• Journal of the Korean Applied Science and Technology
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• v.40 no.4
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• pp.589-605
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• 2023

Soy isoflavones are attracting attention from postmenopausal women because of their beneficial effects on menopausal symptoms. This study was investigated whether a combination of soy isoflavone genistein and swimming exercise (Gen+SE) would have a beneficial synergistic effect on obesity and improvement of liver function compared to the genistein only (Gen) and swimming exercise only (SE) in ovariectomized mice. Ovariectomized mice were randomly divided into control group (Con), Gen, SE, and Gen+SE, and were fed a high-fat diet for 8 weeks. As a result of examining the body weight, weight of white adipose tissue, lipid accumulation of liver, and serum ALT and AST levels, both Gen and SE decreased compared to Con, and Gen+SE decreased more than compared to Gen and SE. The expression of inflammatory cytokines MCP-1, IL-6 and TNF-𝛼 genes in liver decreased in both Gen and SE compared to Con, and were further decreased in Gen+SE compared to Gen and SE. But The expression of adiponectin showed opposite results. The expression of fatty acid oxidation related genes in liver increased in both Gen and SE compared to Con, and were more effectively than increased in Gen+SE compared to Gen and SE. Therefore this study suggests that the interaction between soy isoflavone and swimming exercise is very effective controlling obesity and recovering decreased liver function, and this is caused by promoting fatty acid oxidation in the liver in ovariectomized mice.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.12
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• pp.1769-1775
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• 2010

Menopause is often associated with the incidence of several chronic diseases including osteoporosis, cardiovascular disease, and obesity. The purpose of this study was designed to evaluate the possibility of osteoporosis prevention in postmenopausal women. In this study, we investigated the effects of Ecklonia stolonifera (ES) extracts on bone turnover markers in ovariectomized rats. For this study, the following four groups of 9-week-old Sprague-Dawley rats were evaluated over 6 weeks: normal rats (SHAM), ovariectomized rats (OVX-CON) and ovariectomized rats that were treated with ES extracts. We measured the osteocalcin and C-telopeptide of collagen cross-links (CTx) content, enzyme ALP activity in serum and collagen content in the cartilage, bone, skin and lungs. We found that the levels of indicators of bone metabolism such as alkaline phosphatase (ALP), osteocalcin and CTx were lower in rats in the ES extract group than the OVX-CON group. In addition, the collagen contents in the bone, cartilage, skin and lungs decreased in response to ovariectomy, but the levels of collagen were greater in the bone of rats that were treated with ES extract than in the bone of rats in the OVX-CON group. These results suggest that the ES may be an effective functional food to prevent osteoporosis in postmenopausal women.

• Development and Reproduction
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• v.15 no.4
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• pp.349-357
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• 2011

Since nesfatin-1/NUCB2 involved in the control of appetite and energy metabolism was discovered for the first time in hypothalamus, many reports have shown its expression in various tissues. We also recently demonstrated that nesfatin-1/NUCB2 was expressed in the reproductive organs of mouse. However, no data exist on nesfatin-1/NUCB2 expression, regulation, and secretion in the uterus. Therefore, we examined the expression of nesfatin-1/NUCB2 in mouse uterus and the effects of PMSG and estrogen on its expression. NUCB2 mRNA expression in the uterus was determined by conventional and real-time PCR and nesfatin-1 protein expression was detected by western blotting. In immunohistochemistry staining, nesfatin-1 protein was localized at the epithelial cells of the uterine glands and endometrium. Nesfatin-1 protein binding sites were displayed at the epithelial cells of uterine glands and specific granulocytes including neutrophils. Additionally, to examine if the nesfatin-1/NUCB2 expression in the uterus is regulated by gonadotropin or estrogen, ovariectomized mice were treated with PMSG or $17{\beta}$-estradiol. The expression levels of NUCB2 mRNA in the uterus was significantly increased in the control mice after PMSG treatment, but not in the ovariectomized mice. In contrast, NUCB2 mRNA expression was dramatically increased in the ovariectomized mice after treatment with $17{\beta}$-estradiol. We report here for the first time that nesfatin-1/NUCB2 mRNA and protein express in the mouse uterus and its expression is regulated by estrogen secreted from the ovary, but not gonadotropin from the pituitary.

• Journal of the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1153-1163
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• 2019

In women, obesity rises with menopause. By comparing the dose-dopendent effects of genistein on regulation of body weight and lipid levels with swimming exercise in female ovariectomized (OVX) mice, an animal model of postmenopausal women, the effective dose of genistein on obesity control was investigated. Ovariectomized female mice were divided into control group, swimming exercise group and genistein concentration (0.005%, 0.05%, 0.1% wt/wt) treatment group and all mice fed high-fat diet for 8 weeks. The three different genistein doses as well as swimming decreased body weight, white adipose tissue mass, plasma lipid levels and lipid accumulation in liver, compared with control OVX mice. These decrease effectiveness of genistein showed dose-dependent manner, and is most effective at 0.1% genistein concentration, and paralleled effects of swimming on body weight, white adipose tissue, plasma lipid levels and lipid accumulation in liver. This present findings indicate that optimal dose of genistein in feamle OVX mice have a similar effect to swimming exercise on improvement of obesity. Intake of dietary genistein supplements will help obesity prevention in postmenopausal women.

• Development and Reproduction
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• v.8 no.2
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• pp.99-111
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• 2004

The present study aimed to investigate whether the expression of ADAM-8, 9, 10, 12, 15, 17 and ADAMTS-1 genes is controlled by ovarian steroid hormones. Ovariectomized mice were injected with 17 ${\beta}$-estradiol ($E_2$), progesterone ($P_4$, or $E_2+P_4$. Uterine tissues were processed for RT-PCR and immunoblotting. The results of RT-PCR showed that administration of $E_2$ increases the level of ADAM-8, 12 and ADAM17 expression compared to $P_4$ or control group. In contrast, administration of $P_4$ markedly stimulated the expression of ADAM-9, 10, 15 and ADAMTS-1, whereas $E_2$ did not. Immunoblotting analysis using anti-mouse ADAM polyclonal antibodies demonstrated that $E_2$ alone or $E_2+P_4$ treatment results in the strong expression of ADAM-8, 12 and ADAM17 proteins but $P_4$ alone or control group gave weak expression. In contrast, $P_4$ alone or $E_2$ plus $P_4$ treatment increased the expression level of ADAM-9, 10, 15 and DAMTS-1 proteins. $E_2$ alone or control group did not increase the expression. These results indicate that expression of ADAM-8, 12 and ADAM17 genes is upregulated by $E_2$ and that of ADAM-9, 10, 15 and ADAMTS-1 gene is upregulated by $P_4$.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.177-183
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• 2006

Women's aging made a functional decline at ovary, This functional problem causes estrogen deficiency and many disorders, such as, sexual dysfunction, obesity, osteoporosis, urinary incontinence, skin and all body's aging, etc. We determined the ameliorative effects of some herbal extracts mixture on postmenopausal symptoms in ovariectomized Sprague Dawley rats. Nine-weeks-old female rats were ovariectomized and treated with singled pomegranate extracts (0.40, 1.20 g/kg/day) and mixed pomegranate extracts (1.08, 3.24g/kg/day) for 8 weeks. Oral administration of pomegranate extracts for 8 weeks were increased serum estradiol level and improved the serum osteocalcin, ALP activity and bone specific ALP level. And pomegranate extracts were reduced body weight, adipose tissue. Uterus weight in treated group tended to improve. In addition, the concentrationl of triglyceride and total cholesterol were lower after 8 weeks. HDL-cholesterol levels improved with does-dependency in treated groups. Collagen level on skin and cartilage showed a slight increase at treatment for 8 weeks. $^{\infty}These$ results showed that both of singular extract treatments and extracts mixture treatments were effective on general postmenopausal symptoms at overiectomized rats, and especially, the mixture treatments were more effective than singular treatment. $^{\infty}In$ conclusion, these herbal extracts' mixture showed improvement effect in general factors related with postmenopausal disorders.