• Title/Summary/Keyword: Vitamin D

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Antioxidative Activities of Dried and Fresh Citrus Peels in Jeju (제주산 감귤류 진피와 과피의 항산화 활성)

  • Hyon, Jae-Seok;Kang, Sung-Myung;Senevirathne, Mahinda;Koh, Won-Joon;Yang, Tai-Suk;Oh, Myung-Cheol;Oh, Chang-Kyung;Jeon, You-Jin;Kim, Soo-Hyun
    • Korean journal of food and cookery science
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    • v.26 no.1
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    • pp.88-94
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    • 2010
  • This study was carried out to investigate the total polyphenol and flavonoid contents and antioxidative activities of the methanol extracts of Citrus sunki, C. unshiu and C. natsudaidai peels before and after drying. Total polyphenolic content was high in the citrus peels before drying compared to the dried peels, and highest in the order of C. sunki, C. natsudaidai and C. unchiu. On the other hand, flavonoid content was high in the dried citrus peels than in the citrus peels before drying, and was highest in the order of C. unshiu, C. natsudaidai, C. sunki, but in dried peels it was highest in the order of C. natsudaidai, C. unshiu, C. sunki. DPPH radical scavenging activity was highest in the order of C. natsudaidai, C. unchiu, C. sunki, and that in the citrus peels before drying was higher than in the dried peels. Inparticular, C. natsudaidai peels before drying showed higher activity than vitamin C in 0.5 or 1.0 mg/100 g. Hydrogen peroxide scavenging activity was highest in the order of C. unshiu, C. natsudaidai, and C. sunki in the citrus peels before drying. The dried peels were highest in the order of C. unshiu, C. natsudaidai, C. sunki at 0.5 mg/100 g, but high in order of C. natsudaidai, C. unshiu and C. sunki at more than 1.0 mg/100 g. Inparticular, all C. natsudaidai peels displayed high activity more than 87% at 2.0 mg/100 g. Clear patterns in alkyl radical scavenging activity could not be confirmed in Citrus species whether before or after drying of peels. Hydroxyl radical scavenging activity was highest in the order of C. natsudaidai, C. unshiu and C. sunki but was relatively low compared to the scavenging activity of other activated oxygen species.

Clinical Study on Prenatal care, and Dietary Intakes for Pregnant Women and new Mothers (임산부의 산전관리와 산욕기 영양실태에 관한 연구)

  • Chia, Soon-Hyang;Park, Chai-Soon
    • Journal of Nutrition and Health
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    • v.9 no.4
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    • pp.36-46
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    • 1976
  • This study was projected to provide basic data on prenatal care for future direction in maternity and child care, and also to investigate the diet of women during pregnancy and the period directly afterwards in order to offer to mothers appropriate advice for the improvement of nutritional standards. A clinical study on prenatal care was based on 1054 delivery cases. A nutritional survey was performed on 174 mothers admitted to the department of obstetrics at St. Mary's Hospital during the period of March, 1975 to February, 1976. The results obtained are summarized as follows; I. Clinical study on prenatal care 1) The age distribution showed 59.4% of the mothers were between the ages of 25 to 29 years old. 2) The gestational period was highest between the 37th and 40th gestational weeks. 33.7% of the mothers were primigravidae and 31.8% of them primiparae. 3) 41.3% of the mothers had not received prenatal care or had only received it once before. 4) Induced deliveries were 61.8% and spontantaneous deliveries 38.2%. 61.9% of the mothers had received prenatal care, while those without prenatal care accounted for 61.6% of the total induced deliveries. 5) Low birth weights were 7.7% and 5.0% of the mothers had received prenatal care, while 11.5% had no prenatal care. 6) There were 1.13% of still births, 0.32% of the mothers had prenatal care and the remainder did not have prenatal care. 7) Of those receiving prenatal care, 2.1% showed in the $0{\sim}3$ Apgar score group, 6.3% in the $4{\sim}6$ Apgar score group, and 91.6% in the $7{\sim}10$ Apgar score group. Among the non-prenatally cared for group 5.0% of the newborns were in the $0{\sim}3$ Apgar score group, 9.7% were in $4{\sim}6$ Apgar score group and 85.3% were in the $7{\sim}10$ Apgar score group. 8) Obstetrical complications were developed in 11.86% of the pregnant women when they were hospitalized. Among the group receiving the prenatal care 8.1% of the mothers had obstetrical complications. In the group without prenatal care 17.16% of the mothers had obstetrical complications. The most common obstetrical complication was malpresentation. 9) The first prenatal care was received between the 37th and 40th gestationl weeks. II. Food intake during pregnancy The following are the results from the questionnaires of the mothers concerning diets during pregnancy; 1) Main meals and snacks In 32.2% of the cases, their main meals during the diet amounted to more than was usually eaten at other times. In 67.8% of the cases, their main meals during the diet were the same as that usually eaten. In 22.4% of the cases, snacks during the diet amounted to more than usually eaten at other times. In 77.6% of the cases, snacks during the diet were the same as usually eaten. 2) Itemized list The mothers made a special effort to include certain items in their diets, the following is a breakdown of those items; a. egg, meat, fish 33.3% b. fruit, vegetables 32.2%. c. milk, fruit juice 18.4% d. cake, bread 2.9% e. nothing special 13.2% 3) Milk 44.8% of the mothers had at least one cup of milk everyday. 33.4% of the mothers had at least one cup of milk on occasion. 15.5% of the mothers did not have any milk. 4) Vitamins 39.7% of the mothers had vitamins everyday. 24.7% of the mothers had vitamins occasionally. 35.6% of the mothers did not have any vitamins. 5) Anemic symptoms 9.2% of the mothers very often had anemic symptoms during pregnancy. 39.1% of the mothers often had anemic symptoms during pregnancy. 51.7% of the mothers did not have anemic symptoms at all. 6) Taboos on food 23% of the mothers recognized 'taboos' on food during pregnancy 27% of the mothers displayed on uncertainty about the 'taboos' on food during pregnancy 50% of the mothers displayed indifference toward the taboos. III. Nutritional survey on the new mothers diet. 1) The diets for new mothers can be divided into four categories, such as general diet, low sodium diet, soft diet and liquid diet. 2) Cooked rice and seaweed soup were the main foods for the new mothers as has been the traditional diet for Korean mothers. 3) The average diet contained 1,783g. And the average consumption of the basic food groups per capita per day was 1,265g for cereals and grains, 456g for meats and legumes, 58g for fruits and vegetables, 0g for milk and fish and 4g for fats and oils. 4) In addition to the 1,783g of food in the main diet there was also 142.8g of food taken as snacks. 5) The average daily consumption of calories and nutrients was 2,697 Kcal and 123.4g for proteins, 44.9g for fats, 718.2mg for calcium, 14mg for iron, 2,101.4 I.U. for vitamin A, 0.43mg for thiamine, 1.02mg for riboflavin, 15.88mg for niacin, 5.26mg for ascorbic acid. When these figures are compared with the recommended allowances for new mothers in Korea, the calories and nutrients taken in were satisfactory. But the intake of minerals and vitamins was below the recommended allowance.

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Insulin-like growth factor가 소장 점막 세포 증식에 미치는 영향

  • 윤정한
    • Proceedings of the Korean Nutrition Society Conference
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    • 1995.11b
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    • pp.11-34
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    • 1995
  • Growth hormone (GH) plays a key role in regulating postnatal growth and can stimulate growth of animals by acting directly on specific receptors on the plasma membrane of tissues or indirectly through stimulating insulin-like growth factor (IGF)-I synthesis and secretion by the liver and other tissues. IGF-I and IGF-Ⅱ are polypeptides with structural similarity with proinsulin that stimulate cell proliferation by endocrine, paracrine and autocrine mechanisms. The initial event in the metabolic action of IGFs on target cells appears to be their binding to specific receptors on the plasma membrane. Current evidence indicates that the mitogenic actions of both IGFs are mediated primarily by binding to the type I IGF receptors, and that IGF action is also mediated by interactions with IGF-binding proteins (IGFBPs). Six distinct IGFBPs have been identified that are characterized by cell-specific interaction, transcriptional and post-translational regulation by many different effectors, and the ability to either potentiate or inhibit IGF actions. Nutritional deficiencies can have their devastating consequence during growth. Although IGF-I is the major mediator of GH's action on somatic growth, nutritional status of an organism is a critical regulator of IGF-I and IGFBPs. Various nutrient deficiencies result in decreased serum IGF-I levels and altered IGFBP levels, but the blood levels of GH are generally unchanged or elevated in malnutrition. Effects of protein, energy, vitamin C and D, and zinc on serum IGF and IGFBP levels and tissue mRNA levels were reviewed in the text. Multiple factors are involved in the regulation of intestinal epithelial cell growth and differentiation. Among these factors the nutritional status of individuals is the most important. The intestinal epithelium is an important site for mitogenic action of the IGFs in vivo, with exogenous IGF-I stimulating mucosal hyperplasia. Therefore, the IGF system appears to provide and important mechanism linking nutrition and the proliferation of intestinal epithelial cells. In order to study the detailed mechanisms by which intestinal mucosa is regulated, we have utilized IEC-6 cells, an intestinal epithelial cell line and Caco-2 cells, a human colon adenocarcinoma cell line. Like intestinal crypt cells analyzed in vivo or freshly isolated intestinal epithelial cells, IEC-6 cells and Caco-2 cells possess abundant quatities of both type Ⅰ and type Ⅱ IGF receptors. Exogenous IGFs stimulate, whereas addition of IGFBP-2 inhibits IEC-6 cell proliferation. To investigate whether endogenously secreted IGFBP-2 inhibit proliferation, IEC-6 cells were transfected with a full-length rat IGFBP-2 cDNA anti-sense expression construct. IEC-6 cells transfected with anti-sense IGFBP-2 protein in medium. These cells grew at a rate faster than the control cells indicating that endogenous IGFBP-2 inhibits proliferation of IEC-6 cells, probably by sequestering IGFs. IEC-6 cells express many characteristics of enterocyte, but do not undergo differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation. On the other hand, Caco-2 cells undergo a spontaneous enterocyte differentiation after reaching confluency. We have demonstrated that Caco-2 cells produce IGF-Ⅱ, IGFBP-2, IGFBP-3, and an as yet unidentified 31,000 Mr IGFBP, and that both mRNA and peptide secretion of IGFBP-2 and IGFBP-3 increased, but IGFBP-4 mRNA and protein secretion decreased after the cells reached confluency. These changes occurred in parallel to and were coincident with differentiation of the cells, as measured by expression of sucrase-isomaltase. In addition, Caco-2 cell clones forced to overexpress IGFBP-4 by transfection with a rat IGFBP-4 cDNA construct exhibited a significantly slower growth rate under serum-free conditions and had increased expression of sucrase-isomaltase compared with vector control cells. These results indicate that IGFBP-4 inhibits proliferation and stimulates differentiation of Caco-2 cells, probably by inhibiting the mitogenic actions of IGFs.

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Preventive Effect of Milk Products against Diabetes Mellitus Type 2: A Review (유제품의 제2형 당뇨병 예방 효과: 총설)

  • Kim, Dong-Hyeon;Chon, Jung-Whan;Kim, Hyun-Sook;Kim, Hong-Seok;Song, Kwang-Young;Kim, Young-Ji;Kang, Il-Byung;Lee, Soo-Kyung;Jeong, Dong-Gwan;Kim, Soo-Ki;Seo, Kun-Ho
    • Journal of Dairy Science and Biotechnology
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    • v.33 no.2
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    • pp.129-137
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    • 2015
  • Diabetes mellitus type 2 is a metabolic disorder that is characterized by hyperglycemia (high blood sugar level) in the context of insulin resistance and relative lack of insulin. Recently, much scientific evidence has shown that the risk of diabetes mellitus type 2 could be reduced by dairy intake. A significantly strong relationship has been noted between this disease and dairy intake. In particular, from the different types of fat in dairy foods that were reported to have a beneficial impact, low-fat dairy foods have been found to have the best effect with respect to reducing the risk of diabetes mellitus type 2. Therefore, the role of specific components of dairy foods, such as calcium, vitamin D, dairy fat, and trans-palmitoleic acid, which could be responsible for this effect and for the positive effect of dairy foods in obesity and metabolic syndrome, needs to be identified. There is a strong and relatively consistent body of accumulating evidence indicating that dairy foods may significantly reduce the risk of diabetes mellitus type 2, likely in a dose-response manner. Dairy recommendations should be an essential part of public health guidance, and identifying strategies to increase dairy food consumption to optimal levels is of utmost importance. Hence, this review summarizes various positive effects of dairy foods with respect to reducing the risk of diabetes mellitus type 2, based on available evidence, and discusses the need for further research on preventing or decreasing the risk of diabetes mellitus type 2.

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Yellowish Friable Embryogenic Callus (YFEC) Production and Plant Regeneration from Immature Embryo Cultures of Domestic Maize Cultivars and Genotypes (Zea may L.) (국내 옥수수 품종 및 계통의 미숙배 배양으로부터 Yellowish Friable Embryogenic 캘러스 (YFEC) 생산과 식물체 재생)

  • Cho Mi-Ae;Park Yun-Ok;Kim Jin-Suck;Park Ki-Jin;Min Hwang-Ki;Liu Jang-Ryol;Choi Pil-Son
    • Journal of Plant Biotechnology
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    • v.32 no.2
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    • pp.117-121
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    • 2005
  • Immature embryos of 3 cultivars (Du Me Chal, Mi Baek Chal, Heug Jeom Chal) and 5 genotypes (HW1, KL103, HW3, HW4, KW7) were cultured on medium containing MS salts, Eriksson's vitamins, 1 mg/L 2,4-dichlorophenoxyacetic acid, 25 mM proline, 100 mg/L casamino acid, 3 mM MES, 1.7 mg/L $AgNO_3$ and 20 g/L sucrose (SIM). Frequency of somatic embryo formation on explant of immature embryos showed in HW1 (45.20%), KL103 (5.75%), HW3 (37.20%), HW4 (30.10%), KW70 (55.20%), Mi Baek Chal (18.74%), Heug Jeom Chal (22.41%), Du Me Chal (36.72%) and Hi II type (<10%), respectively. Yellowish friable embryogenic callus (YFEC) such as type II callus of Hi II genotype only produced from the HW3 and Heug Jeom Chal, whereas other cultivars and genotypes were directly formed somatic embryos with late-embryonic stages or expanded yellowish compact somatic embryo with morphological abnormality. The yellowish friable embryogenic callus (YFEC) could be proliferated on the same medium, which were maintained embryogenic capacity for 6 months over. Upon transfer to first regeneration and second regeneration medium, somatic embryos converted to plantlets at a frequency of approximately 100%. However, the expanded somatic embryos with abnormal morphology were slowly proliferated when subcultured on the same medium, and some of them were degenerated or converted to plantlets at a frequency of approximately 25%. Accordingly, The Heug Jeom Chal and HW3 genotype will be further used for development of high frequency transformation system in domestic maize germplasm.

Food and nutrient intake status of Korean elderly by perceived anxiety and depressive condition: data from Korean National Health and Nutrition Examination Survey 2013~ 2015 (한국 노인의 주관적 불안·우울 상태에 따른 식품 및 영양소 섭취 실태 : 2013~ 2015년 국민건강영양조사 자료를 이용하여)

  • Kim, Da-Mee;Kim, Kyung-Hee
    • Journal of Nutrition and Health
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    • v.52 no.1
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    • pp.58-72
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    • 2019
  • Purpose: This study examined the food and nutrient intake of Korean elderly according to the anxiety and depressive condition using the data from the Korea National Health and Nutrition Survey (KNHANES) from 2013 to 2015. Methods: The participants were 3,504 elderly people over 65 years of age (1,523 in men and, 1,981 in women). The dietary information was analyzed using the 24-hour recall data. The anxiety and depressive state was assessed using the self-reported scale EQ-5D in the quality of life dimension. The subjects were divided into the anxiety depression group (AD) and non-anxiety depression group (NAD) according to their anxiety and depressive conditions. Results: In the male elderly, the AD group had a significantly lower education and economic level and higher proportion in living alone than the NAD group. The percentage of eating lunch and dinner alone in the male AD group was higher than that of the NAD group. The female AD group showed less a lower frequency of dinner than the NAD group. The male AD group had a lower consumption of total foods, fish and shellfishes, seaweeds, mushrooms, oils and fats, and seasonings than the NAD group. With regard to the nutrient intake, the male elderly NAD group had more sufficient nutrient intakes than the AD group. In particular, the daily intakes of dietary fiber, riboflavin, niacin, potassium and iron were significantly lower in the AD group. To compare with the nutrient density of the two groups, the vitamin C and niacin intakes were lower in the AD group than in the NAD group. Overall, the nutritional status of the male AD group was significantly lower than that of the NAD group. Meanwhile, the female elderly had showed a smaller difference in nutrient intake according to their anxiety and depressive condition. Conclusion: These results of this study show that more nutritional education and emotional support are needed to improve the nutritional status and health of the male elderly with anxiety or depression.

Effect of Short-term Nutrition Education Camp on Food and Nutrient Intakes of Obese Children (단기간 영양교육 캠프가 비만아동의 식품과 영양소 섭취에 미치는 영향)

  • Shin, Eun-Kyung;Lee, Jin-Hwa;Lee, Yeon-Kyung;Lee, Hye-Sung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.7
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    • pp.987-999
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    • 2005
  • The purpose of this study was to evaluate the effect of short-term nutrition education camp on food and nutrient intakes of obese children. The subjects of the study were 30 obese children in Gumi city who have obesity index over $130\%$. The food consumption of the subjects was surveyed for three days before the camp, for eleven days during the first camp and for three days after the second camp, by food record method. The mean intakes of energy and carbohydrates in obese children were significantly decreased during and after the nutrition education camp, and that of vitamin C was significantly increased after the camp. The mean daily total food intake of the subjects was gradually decreased from 1646.4g before the camp to 1438.6g during the camp and 1412.66g after the camp. Energy and fat intake ratios from grains and milks were significantly decreased after the camp compared with that before the camp, and the energy intake ratio from grains, milks and eggs was significantly low during the camp. The protein intake ratios from grains, potatoes, vegetables and fishes were significantly increased after the camp. The calcium intake ratios from potatoes and milks were significantly increased during and after the camp, and the ratio from eggs was significantly decreased after the camp. The iron intake ratios from potatoes and fishes were significantly increased during and after the camp, and the ratio from grains was significantly low during the camp. The results of the study demonstrated that the short-term nutrition education program positively affected the overall food consumption and nutrients intakes of obese children.

Effects of Taeumin, Soeumin and Soyangin Prescriptions on the Adipocyte Induced by Gold Thioglucose in the Rat (태(太)·소음인(少陰人), 소양인(少陽人)의 처방(處方)이 Gold thioglucose로 유발(誘發)된 백서(白鼠)의 비만병(肥滿病)에 미치는 효과(效果))

  • Kim, Kyung-Yo
    • Journal of Sasang Constitutional Medicine
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    • v.8 no.1
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    • pp.295-317
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    • 1996
  • It is researched to elucidate the effects of Taeumjowuitang(TE,太陰調胃湯), Sibimikwanjungtang(SE, 十二味寬中湯) and Yangkeogsanwhatang(SY,凉膈散火湯) on the obesity induced by gold thioglucose and the differentiation and growth of preadipocyte 3T3-L1 in the mouse. The result were as follows: 1. TE,SE and SY extracts improved the blood level of transaminase in the obese mouse induced by gold thioglucose. 2. TE,SE and SY extracts inhibited the increase of liver fat and body fat in the obese mouse induced by gold thioglucose. 3. TE,SE and SY extracts inhibited the increase of body weight in the obese mouse induced by gold thioglucose. 4. TE,SE and SY extracts inhibited the growth of undifferentiate preadipocyte 3T3-L1. 5. TE,SE and SY extracts showed inhibitory effect on the differentiation of preadipocyte 3T3-L1. The above results suggest that the TE,SE and SY extracts may be used on the obesity induced by the overgrowth and differentiation of adipocyte, and the accumulation of fat in liver and body.

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The effects of proliferation and differentiation on adipocyte 3T3-L1 by prescriptions and herbs of Taeyang-In and Taeum-In (태양인(太陽人), 태음인(太陰人)의 처방(處方)과 약재(藥材)가 지방세포(脂肪細胞)(3T3-L1)의 증식(增殖)·분화억제(分化抑制)에 미치는 영향(影響))

  • Kim, Su-beom;Kho, Byung-hee;Song, Il-byung
    • Journal of Sasang Constitutional Medicine
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    • v.10 no.2
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    • pp.533-564
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    • 1998
  • In order to know the effect of proliferation and differentiation on edipocyte 3T3-L1 by prescriptions and herbs, Taeyangin(太陽人)'s Okapijangcheok-tang(五加皮壯脊湯) Mihudeungsikjangtang Acanthopanacis Cortex(五加皮) Phragmitis Rhizoma(蘆根) and Taeumin(太陰人)'s Taeumjowi-tang(太陰調胃湯) Cheongsimyonja-tang(淸心蓮子湯) Cheongpaesagan-tang(淸肺瀉肝湯) Galkeunbupyong-tang(葛根浮萍湯) Coicis Semen(薏苡仁) Rhei Undulati Rhizoma(大黃) Mori Cortex(桑白皮) Ulmi Cortex(楡根白皮) Holotrichia Vermiculus Kalopanaxii Cortex(海桐皮) Ephedrae Herba(麻黃) Imperatae Rhizoma(白茅根), were used and had some effects. 1. The proliferation effect of edipocyte 1) At the Taeyangin(太陽人)'s prescriptions and herbs, Okapijangcheok-tang(五加皮壯脊湯) Mihudeungsikjang-tang Acanthopanacis Cortex(五加皮) have a control effect at the boiling water-extract and ethyl alcohol-extract. Phragmitis Rhizoma(蘆根) have a control effect at the ethyl alcohol-extract. 2) At the Taeyangin(太陽人)'s prescriptions and herbs, Taeumjowi-tang(太陰調胃湯) Cheongsimyonja-tang(淸心蓮子湯) Cheongpaesagan-tang(淸肺瀉肝湯) Galkeunbupyong-tang(葛根浮萍湯) have a control effect at the boiling water-extract and ethyl alcohol-extract. Coicis Semen(薏苡仁) Rhei Undulati Rhizoma(大黃) Morl Cortex(桑白皮) Ulmi Cortex(楡根白皮) Kalopanaxii Cortex(海桐皮) · Ephedrae Herba(麻黃) of the boiling water-extract, Holotrichia Vermiculus Kalopanaxii Cortex(海桐皮) of ethyl alcohol-extract have a control effect on edipocytes. Rhei Undulati Rhizoma(大黃) Ulmi Cortex(楡根白皮) Ephedrae Herba(麻黃) of high-density have a cyto-toxicity. 2. The differentiation effect of edipocyte 1) At the Taeyangin(太陽人)'s prescriptions and herbs during the natural differentiation, Phragmitis Rhizoma(蘆根) of the boiling water-extract, Okapijangchek-tang(五加皮壯脊湯) Acanthopanacis Cortex(五加皮) of the ethyl alcohol-extract have a cyto-toxicity on the first-differentiation. 2) At the Taeumin(太陰人)'s prescriptions and herbs during the natural differentiation, Ulmi Cortex (楡根白皮) Kalopanaxii Cortex(海桐皮) of the boiling water-extract have a cyto-toxicity on the first-differentiation. Cheongsimyonja-tang(淸心蓮子湯) Ephedrae Herba(麻黃) of ethyl alcohol-extract have a control effect on the redifferentiation. 3) At the Taeyangin(太陽人)'s prescriptions and herbs on the first-differentiation during the induced differentiation, Acanthopanacis Cortex(五加皮) of ethyl alcohol-extract has a control effect. Okapijangchek-tang(五加皮壯脊湯) Acanthopanacis Cortex(五加皮) Phragmitis Rhizoma(蘆根) of the boiling water-extract have a cyto-toxicity. 4) At the Taeumin(太陰人)'s prescriptions and herbs on the first-differentiation during the induced differentiation, Coicis Semen(薏苡仁) Ephedrae Herba(麻黃) Imperatae Rhizoma(白茅根) of the boiling water-extract and Ephedrae Herba(麻黃) of the ethyl alcohol-extract have a control effect. Kalopanaxii Cortex(海桐皮) of the boiling water-extract and the ethyl alcohol-extract has a cyto-toxicity. Considering this result, the Taeyangin(太陽人) Taeumin(太陰人)'s prescriptions and herbs have a control effect on edipocytes during the proliferation. Acanthopanacis Cortex(五加皮), Coicis Semen(薏苡仁) Ephedrae Herba(麻黃) Imperatae Rhizoma(白茅根) have a control effect on edipocytes during the induced differentiation. In the future, for treating a obesity need a vivo assay and hope this study to help to know the mechanisms of obesity.

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The Effects of Isopropyl 2-(1,3-dithioetane-2-ylidene)-2-[N-(4-methyl-thiazol-2-yl)carbamoyl]acetate (YH439) on Potentiated Carbon Tetrachloride Hepatotoxicity (상승적 화학적 간독성에 미치는 YH439의 영향)

  • Kim, Sang-Geon;Cho, Joo-Youn
    • The Korean Journal of Pharmacology
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    • v.32 no.3
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    • pp.407-416
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    • 1996
  • The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

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