• Title/Summary/Keyword: ACAT

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Attenuation of Atherosclerosis by 3,4-Dihydroxy-Hydrocinnamic Acid in Rabbits by Partial Inhibition of ACAT (토끼에서 ACAT 억제에 의한 3,4-다이하이드록시 하이드로시나믹산의 동맥경화 완화 효과)

  • Lee, Mi-Ran;Choi, Jae-Hoon;Yang, Young;Oh, Ki Sook;Jeong, Tae-Sook;Lee, Chul-Ho;Oh, Goo Taeg
    • Korean Journal of Clinical Laboratory Science
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    • v.48 no.4
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    • pp.280-286
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    • 2016
  • Polyphenols have been reported to have beneficial effects on cardiovascular disease. A polyphenolic compound, 3,4-dihydroxy-hydrocinnamic acid (3,4-DHHCA), has been shown to have antioxidative and antitumorigenic activities. However, the effect of 3,4-DHHCA on atherosclerosis is still unknown. Herein, we investigated the effects of 3,4-DHHCA on atherosclerosis in New Zealand White rabbits. Broad and fused fatty streak lesions were found in rabbits fed with high-cholesterol diet for 8 weeks. Administration of 3,4-DHHCA reduced atherosclerotic lesion formation and lesional accumulation of macrophage in rabbits fed with cholesterol diet without systemic or local toxicity. Hepatic acyl-coenzyme A: cholesterol acyltransferase (ACAT) activity was decreased after treatment with 3,4-DHHCA by 22% in cholesterol diet-fed rabbits compared with the control group. These results indicate that 3,4-DHHCA had antiatherogenic effects in rabbits, possibly by partial inhibition of ACAT.

Glycerides from the Aerial Parts of Garland (Chrysanthemum coronarium L.) and Their Inhibitory Effects on ACAT, DGAT, FPTase, and $\beta$-Secretase

  • Song, Myoung-Chong;Yang, Hye-Joung;Cho, Jin-Gyeong;Chung, In-Sik;Kwon, Byoung-Mog;Kim, Dae-Keun;Baek, Nam-In
    • Food Science and Biotechnology
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    • v.18 no.1
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    • pp.95-102
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    • 2009
  • The aerial parts of garland (Chrysanthemum coronarium L.) were extracted in 80% aqueous methanol (MeOH) and the concentrated extract was then partitioned using ethyl acetate (EtOAc), n-butanol (n-BuOH), and $H_2O$, successively. EtOAc and n-BuOH fractions resulted in 4 glycerides with the application of octadecyl silica gel and silica gel column chromatography. The chemical structures of the glycerides were determined using several spectroscopic methods, including nuclear magnetic resonance (NMR) and mass spectrometry (MS) as (2S)-1-O-palmitoyl-sn-glycerol (1), (2S)-1-O-oleoyl-2-O-oleoyl- 3-O-$\beta$-D-galactopyranosyl-sn-glycerol (2), (2S)-1-O-palmitoyl-2-O-linoleoyl-3-O-phosphorouscholine-sn-glycerol (3), and (2S)-1-O-linolenoyl-2-O-palmitoyl-3-O-[$\alpha$-D-galactopyrasyl-($1{\rightarrow}6$)-$\beta$-D-galactopyranosyl]-sn-glycerol (4). The free fatty acids of these glycerides were determined with gas chromatography (GC)-MS analysis following alkaline hydrolysis and methylation. These glycerides demonstrated an inhibitory effect on acyl-CoA: cholesterol acyltransferase (ACAT, compound 1: $45.6{\pm}0.2%$ at $100{\mu}g/mL$), diacylglycerol acyltransferase (DGAT, compound 1: $59.1{\pm}0.1%$ at $25{\mu}g/mL$), farnesyl protein transferase (FPTase, compound 2: $98.0{\pm}0.1%$; compound 3: $55.2{\pm}0.1%$ at $100{\mu}g/mL$), and $\beta$-secretase ($IC_{50}$, compound 4: $2.6{\mu}g/mL$) activity. This paper is the first report on the isolation of these glycerides from garland and their inhibitory activity on ACAT, DGAT, FPTase, and $\beta$-secretase.

Changes of Plasma and Hepatic Lipids, Hydroxy-Methyl-Glutaryl CoA Reductase Activity and Acyl-CoA : Cholesterol Acyltransferase Activity by Supplementation of Hot Water Extracts from Rosa rugosa, Crataegus pinnatifida and Polygonum cuspidatum in High-Cholesterol Fed Rats

  • Lee, Hee-Ja;Park, Myung-Sook
    • Preventive Nutrition and Food Science
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    • v.3 no.4
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    • pp.344-350
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    • 1998
  • Lipid lowering properties from three plant water extracts, Rosa rugosa, Crataegus pinnatifida and Polygonum cuspidatum, were tested by supplementing a 1% high-cholesterol diet with them in rats. Plasma triglyceride levels in Rosa fugosa, Crataegus pinnatifida and Polygonum cuspidatum groups were significantly lower compared to that of the control. by 29% , 24% and 47% respectively. hepatic trigylceride levels in Rosa rugosa and Crataegus pinnatifida groups were significantly lower compared to the control by 11% and 15% respectively. Hepatic HMG-CoA reductase activity in Rosa rugosa group was significantly greater compared to the control by 406%. Hepatic ACAT activity was significantly lower in Polygonum cuspidatum group compared to the control by 28%. by multiple regression results, only plasma cholesterol was associated significantly (p<0.05) with liver HMG-CoA reductase activity. Plasma cholesterol explained 12% of thevariance of the liver HMG-CoA redctase activity. In conclusion, we have showen that hot water extracts from Rosa rugosa, Crataegus pinnatifida and Polygonum cuspidatum lowered plasma triglycerides in rats fed on a high-cholesterol diet. Data suggests that these extracts could potentially prevent or treat hypertriglyceridemia induced by a high fat diet and fatty liver.

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The effects of Pueraria lobata extract on gene expression in liver tissue of rat with estrogen-deficient obesity (갈근이 비만 랫드 간조직의 비만관련 유전자 발현에 미치는 영향)

  • Shin, Yoon Sang;Hwang, Gwi Seo
    • Journal of Society of Preventive Korean Medicine
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    • v.18 no.3
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    • pp.117-128
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    • 2014
  • Objective : It is known that Pueriaria lobata has an anti-osteoporetic effect, anti-cancer effect, anti-pyretic effect, and anti-diabetic effect. The aim of this study was to evaluate anti-obesity effect of Pueriaria lobata extract (PLE), and elucidate the effect of it on gene expression related to lipid metabolism. Method : The experiments were performed with the use of ovariectomized rats as estrogen-deficient obesity model. They were grouped NC (normal control), OC (estrogen-deficient control), PLH (100mg/kg of PLE), PLL (20mg/kg). PLE was orally administered for 6 weeks. Body weights and serum lipid level were estimated, and real-time PCR was performed to investigate the effect of PLE on gene expression in liver. Results : PLE decreased the body weight and serum cholesterol and triglyceride, but increased HDL-cholesterol. And PLE increased leptin, CYP27, CPT1, CYP8B1, ACAT2, LDLR, and SCD1, but reduced $PPAR{\gamma}$, PGC1A, HMG-CoA-R, ACAT1, SCD1, and APoB gene expression in liver tissue of rat with estrogen-deficient obesity. Conclusion : It is concluded that Pueriaria lobata reduced body weight, and its effect was expressed by regulation of gene expression related to lipid metabolism in rats with estrogen-deficient obesity.

Screening of Biologically Active Compound from Edible Plant Sources-IX. Isolation and Identification of Sesquiterpene Lactons Isolated from the Root of Ixeris dentata forma albiflora; Inhibition Effects on ACAT, DGAT and FPTase Activity (식용식물자원으로부터 활성물질의 탐색-IX. 흰씀바귀(Ixeris dentata forma albiflora)뿌리에서 Sesquiterpene Lactone 화합물의 분리 및 구조 동정; ACAT, DGAT 및 FPTase 효소 활성의 저해)

  • Bang, Myun-Ho;Jang, Tae-O;Song, Myoung-Chong;Kim, Dong-Hyun;Kwon, Byoung-Mog;Kim, Young-Kuk;Lee, Hyun-Sun;Chung, In-Sik;Kim, Dae-Keun;Kim, Sung-Hoon;Park, Mi-Hyun;Baek, Nam-In
    • Applied Biological Chemistry
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    • v.47 no.2
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    • pp.251-257
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    • 2004
  • The root of lxeris dentata forma albiflora was extracted with 80% aqueous MeOH and solvent fractionated with EtOAc, n-BuOH and water, successively. From the EtOAc and n-BuOH fractions, four sesquiterpene compounds were isolated through the repeated silica gel and ODS column chromatographies. The chemical structures were determined as zaluzanin C (1), $9{\alpha}-hydroxyguaian-4(l5),10(14),11(13)-triene-6,12-olide$ (2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\alpha}-hydroxyguaian-4(15),10(14 )-diene-6,12-olide$ (3), and $3{\beta}-O-{\beta}- D-glucopyranosyl-8{\beta}hydroxyguaian-10(14)-ene-6,12-olide$ (4) through the interpretation of several spectral data including 2D-NMR. Some showed the inhibitory effects on DGAT (Diacylglycerol acyltransferase), ($IC_{50}$ values of 1, 2: 0.13, 0.10 mM), the catalyzing enzymes of the intracellular esterification of diacylglycerol and FPTase (Famesyl-protein transferase), ($IC_{50}$ values of 1, 2: 0.15, 0.18 mM), the farnesylation enzyme for Ras protein charge of cancer promotion.

Study on the hypochlolesterolemic and antioxidative effects of tyramine derivatives from the root bark of Lycium chenese Miller

  • Cho, Sung-Hee;Park, Eun-Jung;Kim, Eun-Ok;Choi, Sang-Won
    • Nutrition Research and Practice
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    • v.5 no.5
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    • pp.412-420
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    • 2011
  • The aim of the present study was to investigate the hypocholesterolemic effect and potential of tyramine derivatives from Lycii Cortex Radicis (LCR), the root bark of lycium (Lycium chenese Miller) in reducing lipid peroxidation. The activities of enzymes, hepatic 3-hydroxy 3-methylglutaryl (HMG) CoA reductase and acyl-CoA:cholesterol acyltransferase (ACAT) and LDL oxidation were measured in vitro and animal experiments were also performed by feeding LCR extracts to rats. The test compounds employed for in vitro study were trans-N-p-coumaroyltyramine (CT) and trans-N-feruloyltyramine (FT), LCR components, N-(p-coumaroyl)serotonin (CS) and N-feruloylserotonin (FS) from safflower seeds, ferulic acid (FA) and 10-gingerol. It was observed that FT and FS at the concentration of 1.2 mg/mL inhibited liver microsomal HMG CoA reductase activity by ~40%, but no inhibition of activity was seen in the cases of CT, CS, FA and 10-gingerol. Whereas, ACAT activity was inhibited ~50% by FT and CT, 34-43% by FS and CS and ~80% by 10-gingerol at the concentration of 1 mg/mL. A significant delay in LDL oxidation was induced by CT, FT, and 10-gingerol. For the animal experiment, five groups of Sprague-Dawley male rats were fed high fat diets containing no test material (HF-control), 1 and 2% of LCR ethanol extract (LCR1 and LCR2), and 1% of extracts from safflower seed (Sat) and ginger (Gin). The results indicated that total cholesterol level was significantly lower in Saf, LCR2 and Gin groups, and HDL cholesterol level was lower only in Gin group when compared with HF-control group; while there was no difference in the serum triglyceride levels among the five experimental groups. The level of liver cholesterol was significantly lower in LCR1 and LCR2 groups than HF-control Serum levels of TBARS were significantly lower only in LCR2 group when compared with HF-control group. From the observed results, we concluded that LCR can be utilized as a hypocholesterolemic ingredient in combination with ginger, especially for functional foods.

Effects of Water Extracts from Mulberry Leaves on Hepatic HMG-CoA Reductase and Acyl-CoA-Cholesterol Acyl Transferase Activity in Rats Fed High Cholesterol Diets

  • Choi, Jeong-Hwa;Hong, Jung-Hee;Yang, Jeong-Ah;Rhee, Soon-Jae;Park, Mo-Ra
    • Preventive Nutrition and Food Science
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    • v.11 no.1
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    • pp.42-47
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    • 2006
  • This study investigated the effects of mulberry leaf extract on lipid metabolism in rats fed a high cholesterol diet. Sprague-Dawley male rats weighing $100{\pm}10g$ were randomly assigned either to one of two normal diet groups, with (NE group) or without (N group) mulberry extract, or one of four high cholesterol groups containing 1% cholesterol and various levels of dietary mulberry leaf extract. The rats fed high cholesterol diets were subdivided into 4 groups according to level of mulberry extract; Mulberry extract free group (HC group), 0.8% mulberry leaf extract group (HCL group), 1.6% mulberry leaf extract (HCM group) and 3.2% mulberry leaf extract (HCH group). The rats were fed their respective diets ad libitum for 4 weeks. The levels of serum triglyceride, total cholesterol and LDL-cholesterol of the HC group were higher than mulberry leaf extract supplemented groups. In contrast, the levels of serum HDL-cholesterol in groups supplemented with mulberry leaf extract were significantly lower than that of HC group. Hepatic total lipids, triglycerides, and cholesterol were significantly higher in the high cholesterol groups compared to those of the normal group, but were lower in the HCL, HCM and HCH groups than in the HC group. HMG-CoA reductase activity was significantly decreased in the HC and HCL groups compared to the normal and NE groups. However, the activities in the HCM and HCH group were similar to that of the normal group. The activity of acyl-CoA-cholesterol acyl transferase (ACAT) was increased in high cholesterol groups compared to the normal group. However, the activity was lower for all of the high cholesterol groups fed mulberry leaf extracts, and was lowest for the highest supplemented group (HCH), with no significantly difference from the normal group. In conclusion, the reduction in serum and hepatic lipid composition by mulberry leaf extract may be due to its modulation of HMG-CoA reductase and ACAT activities.

Effect of Dandelion Leaf Extracts on Lipid Metabolism in Rats Fed High Cholesterol Diet (민들레잎추출물의 흰쥐 체내 지질대사 개선 효과)

  • 조수열;박지윤;오연진;장주연;박은미;김명주;김광수
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.29 no.4
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    • pp.676-682
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    • 2000
  • The effect of dandelion leaf extracts on lipid metabolism was investigated in high cholesterol-fed rats. Four groups of rats were given a high cholesterol diet containing 10g cholesterol/kg and 2.5 g sodium cholate/kg for 6 weeks. The control group received without dandelion leaf extracts and the other three groups received with one of dandelion leaf extracts (water, ethyl acetate, ether), respectively. Weight gain and feed intake were significantly higher in water group than control group. Serum triglyceride, total cholesterol, cholesteryl ester, chylomicron and VLDL-cholesterol concentratins were lower, whereas HDL-cholesterol and phospholipid concentrations were significantly higher in dandelion leaf extract supplemented-groups than control group. Dandelion extract increased HDL-C/total-C ratio and lowered atherogenic index. Hepatic triglyceride, total cholesterol, free cholesterol and cholesteryl ester concentrations lowered in dandelion leaf extract groups compared to control group. Especially, hepatic triglyceride and free cholesterol levels were lower in ethyl acetate extract group than in water and ether extract groups. Dandelion leaf extract supplements did not affect hepatic phospholipid cencentration. Hepatic HMG-CoA reductase activity was significantly lower in water extract group than the others. ACAT activity was significantly decreased by dandelion extract supplements.

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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.