• Title/Summary/Keyword: 3-Hydroxy-3-methylglutaryl-coenzyme A reductase

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Hypocholesterolemic Effect of Amaranth Squalene (Amaranth esculantus) in Rats Fed a High Cholesterol Diet

  • Kim, Hye-Kyung;Chang, Young-Jeong;Heo, Ho-Jin;Cho, Hong-Yon;Hong, Bum-Shik ;Shin, Dong-Hoon
    • Preventive Nutrition and Food Science
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    • v.8 no.1
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    • pp.13-18
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    • 2003
  • In experiment 1, rats (n=6) fed diet containing 10 g/kg cholesterol for 4 wk (control) with either no amaranth (control), amaranth grain (300 g/kg, AG) or amaranth oil (90 g/kg, AO). Both the AG and AO groups had lower concentration of serum and hepatic cholesterol and triglyceride than the controls (p < 0.05). Fecal excretions of cholesterol and bile acid in AO group increased about 4 fold and 2 fold, respectively, while AG affected only bile acid excretion (p < 0.05). In experiment 2, rats (n=6) were fed the cholesterol diet for 4 wk and injected intraperitoneally with saline (control) or amaranth squalene (AS) for 7d. The hypolipidemic effect of AS was evident in both serum and liver. Fecal excretions of cholesterol and bile acid were greater (p < 0.05) in AS than control. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was reduced in AS group (11.6%, p=0.13). This study suggests that the cholesterol-lowering effect of AS is mediated by greater fecal elimination of steroids through interference with cholesterol absorption.

Screening of Phenolic Compounds with Inhibitory Activities against HMG-CoA Reductase (페놀 화합물로부터 HMG-CoA reductase 저해 활성 물질 탐색)

  • Son, Kun Ho;Lee, Ju Yeon;Lee, Jeong Soon;Kang, Sam Sik;Sohn, Ho Yong;Kwon, Chong Suk
    • Journal of Life Science
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    • v.27 no.3
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    • pp.325-333
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    • 2017
  • High level of plasma cholesterol is strongly associated with the development of atherosclerosis and coronary heart disease. Clinical trials designed to reduce plasma cholesterol level by diet or pharmacological intervention have resulted in marked reduction of disease incidence. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which reduces cholesterol biosynthesis in the liver is the key enzyme of the mevalonate pathway that produces cholesterol. In this study, 71 naturally occurring phenolic compounds were tested for inhibitory activities against HMG-CoA reductase. Eleven compounds out of 71 showed inhibitory activities: three hydrolyzable tannin (geraniin, acetonyl geraniin and pentagalloyl ${\beta}-D-glucose$), four benzoic acid derivatives (benzoic acid, trans-cinnamic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid), and four naphthoquinone derivatives (1,2-naphthoquinone, 1,4-naphthoquinone, plumbagin and shikonin). At the concentration of $10{\mu}g/ml$, 1,4-naphthoquinone inhibited HMG-CoA reductase by 99.4%, and then plumbagin 91.4%, pentagalloyl ${\beta}-D-glucose$ 46.6%, 2,4-dihydroxybenzoic acid 40.9%, shikonin 37.7%, 1,2-naphthoquinone 36.6%, trans-cinnamic acid 32.0%, acetonyl geraniin 30.2%, benzoic acid 28.5%, geraniin 28.3% and 2,5-dihydroxybenzoic acid 22.3%, respectively. $IC_{50}$ values of 1,4-naphthoquinone and plumbagin was $2.1{\mu}g/ml$ and $5.8{\mu}g/ml$, respectively.

Studies on the Development of Antihyperlipidemic Drugs from Oriental Herbal Medicines(I) -Antihyperlipidemic Activities of Oriental Herbal Medicines- (한방약물로부터 항고지혈증 치료약물개발(I) -수종 한약재의 항고지혈증 활성검색-)

  • Jung, Eun-Ah;Kim, Dong-Hyun;Lee, Sang-In;Kim, Nam-Jae
    • Korean Journal of Pharmacognosy
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    • v.30 no.4
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    • pp.368-376
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    • 1999
  • Twenty-four Oriental herbal medicines including Platycodi Radix and Scutellariae Radix, etc., which have been used for the cure of hyperlipidemia, coronary heart, disease were evaluated for the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibition and antioxidant effect on a free radical, 1,1-diphenyl-2-picrylhydrazyl(DPPH) in vitro, and antihyperlipidemic effect on hyperlipidemic rats induced by Triton WR-1339 in vivo. 80% MeOH extract of eight herbs including Scutellariae Radix, Coptidis Rhizoma, Paeoniae Radix Rubra, Moutan Cortex Radicis, Angelicae Gigantis Radix, Bambusae Caulis in Taeniam, Cinnamomi Ramulus and Crataegi Fructus inhibited the HMG-CoA reductase activities and exhibited a radical-trapping action on a stable free radical, DPPH. On Triton WR-1339-induced hyperlipidemic rats, four herbs including Scutellariae Radix, Angelicae Gigantis Radix, Bambusae Caulis in Taeniam and Cinnamomi Ramulus showed respectively the significant suppression of serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and serum transaminase(ALT and AST) activities. From these results, it is suggested that each 80% MeOH extract of Scutellariae Radix, Angelicae Gigantis Radix, Bambusae Caulis in Taeniam and Cinnamomi Ramulus have effective antihyperlipidemic action against hyperlipidemia.

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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.

Screening of Flavonoid Compounds with HMG-CoA Reductase Inhibitory Activities (플라보노이드 화합물로부터 HMG-CoA reductase 저해 활성 물질 탐색)

  • Son, Kun Ho;Lee, Ju Yeon;Lee, Jeong Soon;Kang, Sam Sik;Sohn, Ho Yong;Kwon, Chong Suk
    • Journal of Life Science
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    • v.28 no.2
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    • pp.247-256
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    • 2018
  • 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.

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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The Effects of Ssanggang-tang($Shu\bar{a}ngji\grave{a}ng-t\bar{a}ng$) on Rat with Induced Hyperlipidemia (쌍강탕(雙降湯)이 고(高)cholesterol 식이(食餌)로 유발(誘發)된 고지혈증(高脂血症) 백서(白鼠)에 미치는 영향(影響))

  • Lee, Jae-Hwi;Lim, Seung-Min;An, Joung-Jo;Jo, Hyun-Kyung;Kim, Yoon-Sik;Seol, In-Chan;Yoo, Ho-Rhyong
    • The Journal of Internal Korean Medicine
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    • v.29 no.2
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    • pp.432-442
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    • 2008
  • Objective : Ssanggang-tang(SGT) is noted as an effective method to treat hyperlipidemia in China. The main purpose of this study was analysis of the effects of Ssanggang-tang(SGT) on rats induced with caused hyperlipidemia. Methods : We observed 3 experimental groups: normal, control, and SGT. Rats were provided a normal diet in the normal group, and the other groups were provided a hyperlipidemic diet to induce hyperlipidemia. After 2 weeks, SGT was treated in the SGT group. For 6 weeks, values related to hyperlipidemia were observed in the 3 experimental groups. Results : SGT decreased some values related to hyperlipidemia like total cholesterol, low density lipoprotein cholesterol(LDL cholesterol), triglyceride, acetocoenzyme A acetyltransferase(ACAT), and 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMG-CoA reductase). However, it showed no effect on weight change or high density lipoprotein cholesterol(HDL cholesterol). Conclusion : These results suggest that SGT might be effective in treatment and prevention of hyperlipidemia.

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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.

Anti-aging Effect and Gene Expression Profiling of Aged Rats Treated with G. bimaculatus Extract

  • Ahn, Mi Young;Hwang, Jae Sam;Yun, Eun Young;Kim, Min-Ji;Park, Kun-Koo
    • Toxicological Research
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    • v.31 no.2
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    • pp.173-180
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    • 2015
  • Extract from Gryllus bimaculatus crickets inhibits oxidation at the DNA level, with reduced production of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Microarray analyses were performed with a rat 28K cDNA clone set array to identify the gene expression profiles of aged (10 months old) Wistar Kyoto rats treated for one month with 100 mg/kg G. bimaculatus ethanol extract to assess the effects. The extract produced a meaningful anti-edema effect, evident by the inhibition of creatinine phosphokinase activity. The weights of abdominal and ovarian adipose tissues were reduced and the proportion of unsaturated fatty acids in adipose tissues was increased in an extract dose-dependent manner. Compared with untreated control rats, rats treated with the extract displayed the upregulation of 1053 genes including Fas (tumor necrosis factor receptor superfamily, member 6), Amigo3 (adhesion molecule with an immunoglobulin-like domain), Reticulon 4, 3-hydroxy-3-methylglutaryl-coenzyme (Hmgcr; a reductase), related anti-fatigue (enzyme metabolism), and Rtn antioxidant, and the downregulation of 73 genes including Ugt2b (UDP glycosyltransferase 2 family), Early growth response 1, and Glycoprotein m6a. Data suggest that G. bimaculatus extract may have value in lessening the effects of aging, resulting in a differential gene expression pattern indicative of a marked stress response and lower expression of metabolic and biosynthetic genes.

Effect of Probiotics-Fermented Samjunghwan on Differentiation in 3T3-L1 Preadipocytes (3T3-L1 전지방세포에서 발효 삼정환의 지방 분화 억제 효과)

  • Song, Mi-Young;Bose, Shambhunath;Kim, Ho-Jun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.1
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    • pp.1-7
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    • 2013
  • Samjunghwan (SJH) was fermented using five different probiotic bacterial strains (Lactobacillus plantarum, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillus acidophilus or Bifidobacterium longum) separately. We examined the inhibition of preadipocyte differentiation through Oil Red O staining and analyzed the expression of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EPB{\alpha}$), peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), uncoupling protein (UCP)-2, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which are adipogenic transcription factors. Both Lactobacillus plantarum and Enterococcus faecium-fermented SJH reduced Oil Red O dye staining compared with the same dose of non-fermented SJH. Only Lactobacillus plantarum-fermented SJH inhibited all adipogenic transcription factors and showed the best down-regulation of $PPAR{\gamma}$, UCP-2, and HMG-CoA reductase compared with the same dose of non-fermented SJH. The effect of SJH on the inhibition of preadipocyte differentiation was more prominent from the fermented SJH. Lactobacillus plantarum-fermented SJH, in particular, blocks the expression of $PPAR{\gamma}$, UCP-2, HMG-CoA reductase.