• Title/Summary/Keyword: HMG-1

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Aldose Reductase Inhibitor Fidarestat as a Promising Drug Targeting Autophagy in Colorectal Carcinoma: a Pilot Study

  • Pandey, Saumya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4981-4985
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    • 2015
  • Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

Nutritional Characteristics and Physiological Functionality of Antidementia Acetylcholinesterase Inhibitor-containing Methanol Extract from Sorghum bicolor (항치매성 아세틸콜린에스터레이즈 저해 물질을 함유한 수수(Sorghum bicolor) 메탄올 추출물의 영양학적 특성과 생리 기능성)

  • Song, Jung-Eun;Song, Jung-Hwa;Cho, Soo-Muk;Min, Gyung-Hun;Lee, Jong-Soo
    • The Korean Journal of Food And Nutrition
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    • v.23 no.2
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    • pp.226-232
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    • 2010
  • 새로운 항치매성 건강식품을 개발하기 위해 아세틸콜린에스터레이즈(AChE)를 강력하게 저해하는 추출물을 곡류와 두류의 다양한 추출물로부터 선발한 후 최적 추출 조건을 조사하였다. 추출물 중 수수 메탄올 추출물이 63.4%의 가장 높은 AChE 저해 활성을 보였다. 수수를 80% 메탄올로 $40^{\circ}C$에서 12시간 추출했을 때 최대의 AChE 저해 활성을 나타내었다. AChE를 저해하는 수수 메탄올 추출물의 영양성과 생리 기능성을 조사하였다. 메탄올 추출물은 유리당으로 고형물 100 g당 4.78 g의 포도당과 4.13 g의 자당 및 0.97 g의 과당을 함유하였다. 또한, 수수 메탄올 추출물의 고형물 100 g에 linoleic acid 273.82 mg, oleic acid 215.65 mg, palmitic acid 122.03 mg, stearic acid 4.96 mg을 함유하고 있었고, 주요 유기산으로 주석산 27.45 mg, 말론산 15.43 mg, 사과산 9.94 mg이 메탄올 추출물 1 g에 함유되어 있었다. 수수 메탄올 추출물은 항치매 활성 외에도 콜레스테롤 합성을 저해하는 HMG-CoA reductase 저해 활성이 50.2%이었고, 항산화 활성은 56.1%를 보였다.

Development of Yak-Sun for Excess Syndrome Obesity (1) Effects of Weight, Serum Glucose, Insulin and Lipid Profiles of Oriental Medicinal Herbs with Removal of Dampness through Diuresis (실증성(實證性) 비만을 위한 약선식 개발에 관한 연구 (1) 이습(利濕) 작용이 있는 한약재 혼합 추출물이 체중과 혈청 포도당, 인슐린 농도 및 지질 조성에 미치는 효과)

  • Park Sung-Hye
    • Journal of the East Asian Society of Dietary Life
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    • v.15 no.6
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    • pp.700-706
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    • 2005
  • We are concerned about how to apply the theories of oriental medicine appropriately, which direction should it be taken, and how it should be developed. And it is believed to be essential for the government to make efforts to set a standard and laws to validate the medicinal effects and process of the assessment so that the systematic development can be encouraged, and to prepare guidance for the food development for national health improvement Ihis study was peformed to provide basic data that predict the usefulness of oriental medicinal herbs to remove the dampness through diuresis for excess syndrome obesity with oriental diet therapy cuisine(Yak-Sun). Five oriental medicininal herbs, Coix lachryma-jobi L, Atractylodes lancea DC., Ligusticum wallichii F., Angelica sinensis D., Zingiber officinale R. were collected and made into mixing extracts(OMCE). And we examined the effects of OMCE on body weight serum glucose, insulin and lipid profile improvement in rats fed high fat diets. Sprague-Dawley rae(230-250 g) were randomly divided into five groups : basal diet(normal diet control group, NCG), only high fat diet(High fat control group, HCG), high fat diet and supplemented with 25mg/100g body weight 50mg/100g body weight 75mg/100g body weight by OMCE(HLG, HMG, HHG). These experimental diets were fed for 6 weeks. The OME fed groups decreased more significantly in weight serum glucose insulin and lipids than the high fat control group did. These results imply that the OMCE can be used as a safe and clinically applicable ingredients for diet called Yaksun of excess syndrome obesity in human.

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Pregnancies by In Vitro Fertilization and Embryo Transfer (체외수정과 배이식에 의한 임신성공예에 관한 연구)

  • Ku, Pyong-Sahm;Yoo, Dong-Wha;Lee, Kyu-Won;Rha, Joong-Yul;Hong, Sung-Bong;Bae, In-Ha
    • Clinical and Experimental Reproductive Medicine
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    • v.13 no.2
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    • pp.121-127
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    • 1986
  • We have reviewed 59 cases of patients amoung 65 cases who underwent IVF and ET with reasonable indications irom 1984 and the results as follows. 1. Major indications for IVF and ET were tubal factor (40.7%), unexplained infertility (25.4%), endometriosis (15.3%), failed AID and AIH (10.1 %), and sperm abnormality (8.5%). 2. For superovulation of human oocytes, l00mg of clomiphene citrate and 75 IU of HMG used. The monitoring of oocyte maturation was bone by ultrasound examination and serum 17-${\beta}$ estradiol, LH values. The peak $E_2$ value was 956.36${\pm}$702.13 pg/ml. 3. The oocytes were obtained by laparoscopy 24-36 hours after the injection of HCG. 4. The mean numbers of follicles at laparoscopy was 3.06 and the successful rate of laparoscopy was 79.7%. 5. And 165 follicles were aspirated from which 98 oocytes were recovered, 59.4% of all follicles had at least one oocyte aspirated. 21.4% of the eggs were mature, 52.0% were moderate, 26.5%. were immature. 6. 67.3% of oocytes were cleaved and were transferred at 4-6 cell stages. 7. Four pregnancies including one chemical pregnancy and one spontaneous abortion were established by ${\beta}$-subunit, u-hCG and ultrasound examinations.

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Induction of Ovulation with Clomiphene Citrate (Clomiphene Citrate를 이용한 배란유도에 관한 연구)

  • Moon, S.Y.;Yoon, B.K.;Yoon, B.H.;Kim, J.G.;Lee, J.Y.;Chang, Y.S.
    • Clinical and Experimental Reproductive Medicine
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    • v.12 no.2
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    • pp.15-23
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    • 1985
  • Therapy for anovulation represents one of the more gratifying and successful type of infertility management. Despite the introduction of bromocriptine, human menopausal gonadotropin (HMG), and gonadotropin releasing hormone (GnRH), clomiphene citrate remains the mainstay of ovulation induction therapy. There is wide variability in reported rates of ovulation induction (57-91%) and conception (25-43%) following clomiphene therapy. Factors contributing to this variability among different reports are the differences in dosage and duration of therapy, different criteria utilized in selecting patients for clomiphene therapy and different luteal phase parameters of presumptive ovulation. A review of recent experience with clomiphene citrate in the Department of Obstetrics and Gynecology in Seoul National University from January, 1983 to May, 1985 yields the following conclusions: 1. Ovulation rate per total patients treated was, 69.0% 2. Pregnancy rate per total patients treated was 31.7%, and that per total patients ovulated was 45.9%. 3. Ovulation rate at the dosage level up to 150 mg/day (50.3-53.8%) was somewhat higher than that at 200 mg/day or more (33.3-34.6%), and pregnancy rate per total patients treated was comparable at each dosage level. 4. Ovulation rate per total patients ovulated at each dosage level, where ovulation and conception occurred, showed a decreasing tendency as the dosage increased, but pregnancy rate per total patients conceived was comparable except at 200 mg/day. 5. Cumulative pregnancy rate per total patients conceived in each ovulatory cycle was 68.9% in 3 cycles, 88.9% in 4 cycles, and 100% in 6 cycles.

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Exponential Rise Rate of Serum Estradiol Concentrations and the Outcome of Ovulation Induction by Human Menopausal Gonadotropin (혈청 Estradiol 농도의 지수함수적 증가율이 Human Menopausal Gonadotropin 배란유도 결과에 미치는 영향)

  • Bai, K.B.;Kim, J.G.;Moon, S.Y.;Lee, J.Y.;Chang, Y.S.
    • Clinical and Experimental Reproductive Medicine
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    • v.14 no.2
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    • pp.119-126
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    • 1987
  • Exponential rise rate(ERR) of serum estradiol concentrations during active follicular phase was calculated for 49 ovulation induction cycles by human menopausal gonadotropin to know the ovulation induction outcome according to ERR classified into 3 groups with low, moderate and high ERR values(Group I${\leqq}$0.3, 0.3${\leqq}$0.6,Group III>0.6). The results were summarised as follows : 1. No significant difference in the dosage of human menopausal gonadotropin was identified in each group. 2. The mean serum estradiol concentration at the day of human chorionic gonadotropin injection in Group II and Group ill was significantly higher than that in Group I . 3. The mean diameter of leading follicles at the day of human chorionic gonadotropin injection showed no significant difference in each group. 4. No significant difference in the ovulation rate was observed in relation to ERR. How ever, 20% and 20.8% of pregnancy rate in Group I and Group II were achieved while no pregnancy was occurred in Group III. 5. The ovarian hyperstimulation frequency was significantly higher in Group ill that in Group I and Group II. In conclusion, the study suggests that exponential rise rate of serum estradiol is a useful tool in HMG ovulation induction by preventing ovarian hyperstimulation without reducing pregnancy success rate.

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Drug research and development tend to hyperlipidemia (이상지질혈증과 치료제 연구개발 경향)

  • Seol, In-Chan
    • Journal of Haehwa Medicine
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    • v.18 no.2
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    • pp.1-12
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    • 2009
  • Most of the cholesterol is synthesized by liver in the body while about one of third is taken via dietary. The main functions of cholesterol is to protect membranes in cell surface, avoid the arterial bleeding by hypertension, and prolong the life of erythrocytes, and so on. However, overload of cholesterol leads to arteriosclerosis associated with leading death cause. Lack of physical activity, emotional and environmental stress, and low intake of protein or vitamin E induce the unbalance between HDL- and LDL-cholesterol so become a basis of ischemic disorders in heart, brain and elsewhere in the body. So far, four major classes of medications for hyperlipidemia are HMG-CoA reductase inhibitors (statins), bile acid sequestrants, nicotinic acid, and fibric acids. The statins can lower LDL and levels triglyceride, but may induce myopathy and an elevation of liver enzyme levels. The bile acid sequestrants lower LDL levels and raise HDL levels with no effect on triglyceride levels but side effects of gastrointestinal (GI) distress, constipation, and a decrease in the absorption of other drugs. Nicotinic acid and fibric acids lower LDL and triglyceride levels with showing flushing, hyperglycemia, hyperuricemia, GI distress, and hepatotoxicity dyspepsia, gallstones, myopathy, and unexplained noncardiac death as adverse effects. Above western drugs lower cholesterol by 15 to 30% while all have notable adverse effects. In traditional medicine, hyperlipidemia is regarded as retention of phlegm and fluid disease. Etiology and pathogenesis of hyperlipidemia is basically based on Spleen-Deficiency and Phlegm-Stagnation, accumulation and stasis of -heat, and Qi & blood stagnation induced by Phlegm-damp, water-dampness, and blood stasis. Thereby, strengthening Spleen and dissolving Phlegm, clearing away heat and diuresis, and supplementing Qi and activating blood circulation are commonly used therapeutic methods for hyperlipidemia. The traditional herbal medicine, have been used for patients with CVA, hypertension or hyperlipidemia in Oriental hospital or Oriental clinic. The lock and key theory is used to develop most of western medicine, however many diseases are caused by mixed factors in body-complex system. We expect that Oriental pharmacological theory could be newborn as a novel drug showing high advantage of blood levels of lipidsand QOL of performance without side effects.

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Effect of Yagwan-cheunghyeoltang on Obesity in Rats Induced by High Fat Diet (야관청혈탕이 고지방식이로 유도된 흰쥐의 비만 억제에 미치는 영향)

  • Park, Sang-Woo;Cho, Chung-Sik;Kim, Chul-Jung
    • The Journal of Internal Korean Medicine
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    • v.32 no.2
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    • pp.170-187
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    • 2011
  • Background : Obesity, the syndrome caused by a high fat diet, is a disease. At the same time, obesity causes diabetes mellitus, hyperlipidemia, and cardiovascular disease. Recently, its prevalence rate is increasing. Yagwan-cheunghyeoltang (YCT) used in this experiment is the prescription of Yagwanmoon added to Cheunghyeol-tang which is reported to be very effective in weight loss controlling and serum cholesterol. It is also reported that Yagwanmoon has significant antioxidant effects and YCT has a significant effect on blood glucose control. Objectives : This study was conducted to experimentally evaluate the effects of YCT on obesity in rats induced by high fat diet. Methods : The experiment was conducted with 4-week-old male rat s divided into 5 groups. They were a normal diet group, a high fat diet group, a positive drug control group, a 1% YCT group, and a YCT 3% group, and were tested for eight weeks. After four weeks of inducing obesity by a high fat diet, rats were allowed to lose weight by following the normal diet group, approximately 30% compared with 10 rats in each group were determined as still obese. Changes in body weight and organ weight and serum cholesterol, triglyceride, glucose-density, low density lipoprotein cholesterol, antioxidant activity were checked. Results : In the experimental groups, we observed weight loss and visceral fat reduction, improvement of liver function, reduction of serum glucose, activation of HMG-CoA reductase inhibitor, reduction of concentrations of leptin and it showed a significant effect on antioxidants and lipid peroxidation. Conclusions : YCT has significant effects on the regulation of hyperlipidemia and lipid peroxidation associated with obesity and has significant effects on, antioxidants and lipid peroxidation, too. Additional clinical studies are needed.

The Effects of Gangzitongmaekeum on Antioxidation Activity and Dietary Hyperlipidemia-induced Mice (강지통맥음(降脂通脈飮)이 항산화 활성과 고지혈(高脂血) 유발(誘發) 백서(白鼠)에 미치는 영향(影響))

  • Cha, Kwan-Bae;An, Joung-Jo;Jo, Hyun-Kyung;Yoo, Ho-Rhyong;Kim, Yoon-Sik;Seol, In-Chan
    • The Journal of Internal Korean Medicine
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    • v.29 no.3
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    • pp.703-715
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    • 2008
  • This experiments was performed to determine the effects of Gangzitongmaekeum(降脂通脈飮 : GTE) on antioxidation activity and hyperlipidemia induced by hypercholesterolemic diet in mice. The results obtained were as follows : 1. GTE showed a safety in cytotoxicity and toxicity of human fibroblast cells and liver. 2. GTE showed DPPH scavenging activity, superoxide dismutase (SOD)-like activity and inhibitory effect on reactive oxygen species (ROS). 3. GTE treated mice showed body and liver weight decrease, compared to the hyperlipidemia-induced control group. 4. GTE decreased total cholesterol and LDL cholesterol levels significantly, but HDL cholesterol levels not significantly. 5. GTE decreased triglyceride levels significantly. 6. Glucose levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. 7. Albumin levels in GTE treated mice were similar with the hyperlipidemia-induced control group. 8. The lipophagy in liver compared with the control group tended to be decreased in GTE treated mice. In the change of aorta, the cell was regular and boundary of vessel wall was clear, compared to the hyperlipidemia-induced control group. 9. TBARS levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. 10. The change of SOD and catalase activity significantly increased compared to the hyperlipidemia-induced control group. 11. ACAT mRNA level and HMG-CoA reductase mRNA levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. Conclusion : These results suggest that Gangzitongmaekeum is effective in antioxidation activity and dietary hyperlipidemia-induced mice.

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Enhancement of artemisinin content by constitutive expression of the HMG-CoA reductase gene in high-yielding strain of Artemisia annua L.

  • Nafis, Tazyeen;Akmal, Mohd.;Ram, Mauji;Alam, Pravej;Ahlawat, Seema;Mohd, Anis;Abdin, Malik Zainul
    • Plant Biotechnology Reports
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    • v.5 no.1
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    • pp.53-60
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    • 2011
  • Artemisinin is effective against both chloroquine-resistant and -sensitive strains of Plasmodium species. However, the low yield of artemisinin from cultivated and wild plants is a serious limitation to the commercialization of this drug. Optimization of artemisinin yield either in vivo or in vitro is therefore highly desirable. To this end, we have overexpressed the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) gene (hmgr) from Catharanthus roseus L. in Artemisia annua L. and analyzed its influence on artemisinin content. PCR and Southern blot analyses revealed that the transgenic plants showed stable integration of the foreign hmgr gene. The reverse transcriptase-PCR results suggested that the hmgr was expressed at the transcriptional level in transgenic lines of Artemisia annua L., while the high-performance liquid chromatography analysis showed that artemisinin content was significantly increased in a number of the transgenic lines. Artemisinin content in one of the A. annua transgenic lines was 38.9% higher than that in non-transgenic plants, and HMGR enzyme activity in transgenic A. annua L. was also higher than that in the non-transgenic lines.