• Title/Summary/Keyword: HMG-CoA

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Anti-Obesity Effects of Kimchi Tablet Composition in Rats Fed High-Fat Diet (김치를 이용한 타블렛 조성물이 고지방식이로 유도된 흰쥐의 비만 억제에 미치는 효과)

  • Kong, Yeon-Hee;Cheigh, Hong-Sik;Song, Young-Ok;Jo, Youn-Ock;Choi, Sang-Yoon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.12
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    • pp.1529-1536
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    • 2007
  • Anti-obesity effects of kimchi tablet composition (KTC) were investigated with male Sprague-Dawley rats fed high-fat diet for 8 weeks. Fifty rats were classified to 4 groups: normal diet (ND), high fat diet (HFD), HFD+KTC 5% and HFD+KTC 10% for feeding experiments. This research showed that the final weight, weight gain, food efficiency ratio and organ weight were decreased by the addition of KTC compared to those of HFD group. Amount of subcutaneous fat of KTC groups were 13.6% and 21.3%, respectively. The plasma triglyceride concentration of KTC groups was lower than that of high fat diet group. Plasma cholesterol concentration of all four groups were not significantly different. HDL-cholesterol concentration of KTC groups was higher than those of high fat diet group. In addition, triglyceride and cholesterol concentrations in the liver and heart were reduced by the addition of KTC. Moreover, triglyceride concentration of fecal and hepatic HMG-CoA reductase activity were increased in KTC group. These results suggested that KTC might be useful for obesity control and good source of functional kimchi tablet.

Hypocholesterolemic metabolism of dietary red pericarp glutinous rice rich in phenolic compounds in mice fed a high cholesterol diet

  • Park, Yongsoon;Park, Eun-Mi;Kim, Eun-Hye;Chung, Ill-Min
    • Nutrition Research and Practice
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    • v.8 no.6
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    • pp.632-637
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    • 2014
  • BACKGROUND/OBJECTIVES: The purpose of the current study was to investigate the effect of red pericarp glutinous rice rich in polyphenols (Jakwangchalbyeo, red rice) on serum and hepatic levels of cholesterol and hepatic protein expression linked to synthesis and degradation of cholesterol in a hypercholesterolemic mice diet as compared with brown rice. MATERIALS/METHODS: C57BL/6 male mice were randomly divided into four groups (n = 5 each), which were fed different diets for a period of 12 weeks: American Institute of Nutrition (AIN)-93G diet, AIN-93G diet with 2% cholesterol, brown rice with 2% cholesterol, or red rice with 2% cholesterol. RESULT: Consumption of red rice resulted in a significant decrease in serum level of low-density lipoprotein cholesterol and hepatic levels of triglyceride and total-cholesterol. Expression of acyl-coenzyme A cholesterol acyltransferase-2 (ACAT-2), sterol regulatory element binding protein-2 (SREBP-2), and 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase was decreased, while expression of phosphorylated adenosine monophosphate activated protein kinase (p-AMPK)/AMPK ratio, cholesterol 7-${\alpha}$-hydroxylase (CYP7a1), and sterol 12-${\alpha}$-hydroxylase (CYP8b1) was increased in mice fed red rice. Brown rice had similar effects on cholesterol metabolism, but the effect of red rice was significantly greater than that of brown rice. CONCLUSIONS: The current study suggested that red rice had a hypocholesterolemic effect by lowering hepatic cholesterol synthesis through ACAT-2, HMG-CoA reductase, and SREBP-2, and by enhancing hepatic cholesterol degradation through CYP7a1 and CYP8b1 in mice fed a hypercholesterolemic diet.

Hypocholesterolemic Soybean Peptide (IAVP) Inhibits HMG-CoA Reductase in a Competitive Manner

  • Pak, Valeriy V.;Koo, Min-Seon;Lee, Na-Ri;Oh, Su-Kyung;Kim, Myung-Sunny;Lee, Jong-Soo;Kwon, Dae-Young
    • Food Science and Biotechnology
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    • v.14 no.6
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    • pp.727-731
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    • 2005
  • Synthesized Ile-Ala-Val-Pro (IAVP) peptide, which has the highest hypocholesterolemic effect among a number of synthesized derivatives of Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA) isolated from 11S globulin of soy protein by pepsin digestion, was selected for investigation in the present study. Using a recombinant Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), we studied in detail the inhibition of this enzyme by IAVP and compared the action of this peptide to that of lovastatin, a known competitive inhibitor of this enzyme. The concentration of IAVP required for 50% inhibition ($IC_{50}$) of HMGR activity in given experimental conditions was $340\;{\mu}M$. Kinetic analysis revealed that the studied peptide is a competitive inhibitor of HMGR with respect to both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and nicotinamide adenine dinucleotide phosphate (NADPH), with an equilibrium constant of inhibitor binding ($K_i\;=\;[E][I]/[EI]$) of $61{\pm}1.2\;{\mu}M$ and $157{\pm}4.4\;{\mu}M$, respectively. At the same conditions, $K_i$ and $IC_{50}$ for lovastatin were $2.2{\pm}0.1\;nM$ and 12.5 nM, respectively. Thus, the given peptide interacts with HMGR as a bisubstrate, consequently blocking access of both substrates to the active sites. The achieved results suggest the design of new peptide sequences having a higher relative affinity to binding sites of this enzyme and an enhancement of their hypocholesterolemic properties.

Protective Effect of Mulberry Leaf and Yacon Extract Induced Hyperlipidemia in Obese Rats

  • Lim, Yong;Oh, Ji Hye;Park, Un Kyu;Huh, Man Kyu;Hwang, Seock-Yeon
    • Biomedical Science Letters
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    • v.26 no.2
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    • pp.101-108
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    • 2020
  • There has been a lot of interest in medicinal effects for hyperlipidemia from the natural product since the therapy of atherosclerosis has emerged as social concern. Rats were acclimated to the feeding environment for one week and induced to obesity with high fat diet during 4 weeks until their body weight were more than 30% of normal range. To evaluate the effect of hyperlipidemia of mulberry leaf of Morus alba and yacon tuber of Smallanthus sonchifolia extracts (MLYT), 1%, 3%, 5% of MLYT were treated to Sprague-Dawley rats. Aspartate transaminase (AST) was significantly increased 26.2% in high fat diet group (G2) compared to normal diet group (G1) (P<0.05). But AST were significantly decreased in high fat diet with 0.5% hydroxycitric acid diet group (G3) and all the MLYT treated groups compared to G2. Total cholesterol, low-density lipoprotein (LDL), triglycerides and phospholipids were observed significant improvements in the MLYT-treated groups (P<0.05). These improvements in liver and feces were further supported by the lipid content. MLYT remarkably suppressed the level of lipid peroxidation caused by high-fat diet in rats. The level of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase activity. As a result, the proper combination of mulberry leaves and yacon tuber extract will have a synergistic effect on hyperlipidemia. These results indicate that MLYT could be a candidate for the improvement of hyperlipidemia.

Anti-Oxidative and Anti-Obesity Effect of Combined Extract and Individual Extract of Samjunghwan (혼합추출 및 개별추출 방식의 삼정환의 항산화 및 항비만효과)

  • Han, Kyungsun;Wang, Jinghwa;Lim, Dongwoo;Chin, Young-Won;Choi, Young Hee;Choi, Han-Seok;Lee, Myeong-Jong;Kim, Hojun
    • Journal of Korean Medicine for Obesity Research
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    • v.14 no.2
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    • pp.47-54
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    • 2014
  • Objectives: This study is to confirm the effect of combined extract and individual extract of Samjunghwan (SJH) in anti-oxidative and anti-obesity effect. Methods: Combined ethanol extract of readily made SJH and individual ethanol extract of Atractylodes japonica, Cortex lycii radicis, and Morus alba Linne was combined after the extraction. To evaluate the anti-oxidative effect of SJH, total phenol compound and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging ability were conducted. Real-time quantitative-polymerase chain reaction analysis of transcription factor peroxisome proliferator-activated receptror ${\gamma}$ ($PPAR{\gamma}$), adenosine monophosphate-activated protein kinase (AMPK)-${\alpha}1$, tumor necrosis factor-${\alpha}$ ($TNF{\alpha}$) and 3-hydroxy-3-methylglutaryl CoA reducatase (HMG-CoA reductase) were done with 3T3-L1 cells to investigate the ant-obesity effect. Also, cell viability analysis were done to see to toxicity of SJH. Results: Individual extract of SJH showed significant decrease in $TNF{\alpha}$ and AMPK transcription while $PPAR{\gamma}$ showed significant increase. Combined extract and individual extract of SJH both showed decrease in HMG-CoA reductase. DPPH free radical scavenging ability and total phenol compound was analogous between two groups. Conclusions: Individual extract of SJH appears to be more effective in anti-oxidation and anti-obesity effect compared to combined extract of SJH.

The Risk of Rosacea According to Chronic Diseases and Medications: A 5-Year Retrospective, Multi-Institutional Case-Control Study

  • Son, Jee Hee;Chung, Bo Young;Jung, Min Je;Choi, Yong Won;Kim, Hye One;Park, Chun Wook
    • Annals of dermatology
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    • v.30 no.6
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    • pp.676-687
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    • 2018
  • Background: Rosacea is associated with chronic systemic disease. However, research is lacking in Asian countries. Objective: To evaluate the association between rosacea and cardiovascular diseases (CVDs) related systemic comorbidities, and the use of antihypertensive and antihyperlipidemic drugs in Korea. Methods: A five-year retrospective study, using hospital database, was conducted in five medical centers for five years. Totally 1,399,528 patients were evaluated. Results: The overall frequency for diagnosed rosacea was 0.18% over five years (2,536 rosacea patients). Patients with diabetes and patients with dyslipidemia were more likely to have rosacea (odd ratio [OR] 2.724, 95% confidence interval [CI] 1.295~5.730, p=0.016; OR 1.788, 95% CI 1.445~2.212, p<0.001). Patients with CVD were less likely to have rosacea (OR 0.431, 95% CI 0.244~0.760, p=0.003). Patients with ${\alpha}$-blocker prescriptions and patients with ${\beta}$-blocker prescriptions showed a tendency diagnosed with rosacea frequently (OR 1.963, 95% CI 1.200~3.212, p=0.006; OR 3.939, 95% CI 3.512~4.419, p<0.001). Patients with [beta]-hydroxy-[beta]-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and those with fibrate, were prone to have rosacea (OR 1.599, 95% CI 1.390~1.839, p<0.001; OR 1.660, 95% CI 1.056~2.609, p=0.026). As adjusted results, among the patients who took HMG-CoA reductase inhibitor without dyslipidemia, rosacea was less likely to be diagnosed (OR 0.780, 95% CI 0.620~0.982, p=0.034). Conclusion: Rosacea is associated with chronic diseases and drugs.

Preparation and Characterization of Simvastatin Solid Dispersion using Aqueous Solvent

  • Kim, Kwang-Hyeon;Park, Jun-Bom;Choi, Won-Jae;Lee, Han-Seung;Kang, Chin-Yang
    • Journal of Pharmaceutical Investigation
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    • v.41 no.4
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    • pp.239-247
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    • 2011
  • Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. Simvastatin has good permeability, but it also has low solubility (BCS class II), which reduces its bioavailability. To overcome this problem, a solid dispersion is formed using a spray-dryer with polymeric material carrier to potentially enhance the dissolution rate and extend drug absorption. As carriers for solid dispersion, Gelucire$^{(R)}$44/14 and Gelucire$^{(R)}$ 50/13 are semisolid excipients that greatly improve the bioavailability of poorly-soluble drugs. To avoid any toxic effects of an organic solvent, we used aqueous medium to melt Tween$^{(R)}$ 80 and distilled water. The structural behaviors of the raw materials and the solid dispersion were analyzed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The DSC and PXRD data indicated that the crystalline structure of simvastatin was transformed to an amorphous structure through solid dispersion. Then, solid dispersion-based tablets containing 20 mg simvastatin were prepared with excipients. Dissolution tests were performed in distilled water and artificial intestinal fluid using the USP paddle II method. Compared with that of the commercial tablet (Zocor$^{(R)}$ 20 mg), the release of simvastatin from solid dispersion based-tablet was more efficient. Although the stability study is not complete, this solid dispersion system is expected to deliver poorly water-soluble drugs with enhanced bioavailability and less toxicity.

Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase

  • Lew, Lee-Ching;Choi, Sy-Bing;Khoo, Boon-Yin;Sreenivasan, Sasidharan;Ong, Kee-Leong;Liong, Min-Tze
    • Food Science of Animal Resources
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    • v.38 no.2
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    • pp.350-361
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    • 2018
  • Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.

The Effects of Gamijihwang-tang(GJT) on Hyperlipidemia in Rats (가미지황탕(加味地黃湯)이 고지혈증(高脂血症) 관련(關聯) 인자(因子)에 미치는 영향)

  • Park, So-Ae;Jo, Hyun-Kyung;Yoo, Ho-Ryong;Kim, Yoon-Sik;Seol, In-Chan;An, Jung-Jo
    • The Journal of Internal Korean Medicine
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    • v.30 no.2
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    • pp.338-354
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    • 2009
  • Objective : Gamijihwang-tang(GJT) has been used as a therapeutic agent for hyperlipidemia in oriental medicine for several years. This study was performed to investigate the effects of GJT on hyperlipidemia in rats using diverse biological methods. Method : Hyperlipidemia was induced by a hyper-lipidemic diet fed for 4 weeks. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride, and glucose were measured in the serum after an oral administration of GJT. Lipid peroxidase, SOD, catalase, ACAT, and HMG-CoA were measured in liver after oral administration of GJT. Result: 1. GJT showed safety against cytotoxicity and toxicity in liver. 2. GJT significantly decreased rat's body and liver weight. 3. GJT significantly decreased serum total cholesterol and LDL-cholesterol, but increased serum HDL-cholesterol. 4. GJT significantly decreased serum triglyceride and glucose. 5. GJT significantly decreased lipid peroxidation and increased SOD and catalase in liver. 6. GJT significantly decreased ACAT and HMG-CoA reductase of cholesterol manifestation in liver. Conclusions : These results suggest that GJT might be effective in treatment and prevention of hyperlipidemia.

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Effects of Methanol Extract of Prosomillet on Cholesterol and Fatty Acid Metabolism in Rat

  • Cho, Sung-Hee;Jung, Seung -Eun;Lee, Hye-Kyung;Ha, Tae-Youl
    • Preventive Nutrition and Food Science
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    • v.4 no.3
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    • pp.188-192
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    • 1999
  • To study effects of methanol extract of prosomillet on lopid metabolism , five groups of male Sprang-Dawley rats weighing 116$\pm$9 g were fed test diets for four weeks. The five diets consisted of one low fat(5% w/w) diet containing starch as carbohydrate source(normal) and four high fat diets(15% w/w) containing 40.5%(w/w)sucrose(control) and additional 80% nethanol extractof prosomillet at the levels of 0.3% and 1%(w/w) or prosomillet powder at the level of 20%(w/w). Serum level of total cholesterol was a little higher but that of triglyceride was 41% lower in 20% (w/w) prosomillet powder group than in the control group. The cholesterol levels of two Liver cholesterol levels were lower and phospolipid levels higher in all three prosomillet powder group . Fecal excretionof bile acid was most increased in the prosomillet powder group among all five test groups. Acitivity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase was significantly lower in 0.3% methanol extract fed group than the control and also appeared to be reduced in 1% extract fed one, wherease those of 20 cholesterol 7$\alpha$-hydroxylase were not different among the five groups. Activities of liver cytosilic glucose-6-phosphate dehydrogenase(G6PDH) and malic enzyme were decreased in 0.3% prosomillet methanol extract and 20% powder groups. The results indicate that in addition to fiber, certain active components in prosomillet have potential to exert hypolipidemic effects via regulating hepatic cholesterogenesis and lipogenesis.

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