• Title/Summary/Keyword: ACAT1

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Corn silk extract improves cholesterol metabolism in C57BL/6J mouse fed high-fat diets

  • Cha, Jae Hoon;Kim, Sun Rim;Kang, Hyun Joong;Kim, Myung Hwan;Ha, Ae Wha;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • 제10권5호
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    • pp.501-506
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    • 2016
  • BACKGROUNG/OBJECTIVES: Corn silk (CS) extract contains large amounts of maysin, which is a major flavonoid in CS. However, studies regarding the effect of CS extract on cholesterol metabolism is limited. Therefore, the purpose of this study was to determine the effect of CS extract on cholesterol metabolism in C57BL/6J mouse fed high-fat diets. MATERIALS/METHODS: Normal-fat group fed 7% fat diet, high-fat (HF) group fed 25% fat diet, and high-fat with corn silk (HFCS) group were orally administered CS extract (100 mg/kg body weight) daily. Serum and hepatic levels of total lipids, triglycerides, and total cholesterol as well as serum free fatty acid, glucose, and insulin levels were determined. The mRNA expression levels of acyl-CoA: cholesterol acyltransferase (ACAT), cholesterol 7-alpha hydroxylase (CYP7A1), farnesoid X receptor (FXR), lecithin cholesterol acyltransferase (LCAT), low-density lipoprotein receptor, 3-hyroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), adiponectin, leptin, and tumor necrosis factor ${\alpha}$ were determined. RESULTS: Oral administration of CS extract with HF improved serum glucose and insulin levels as well as attenuated HF-induced fatty liver. CS extracts significantly elevated mRNA expression levels of adipocytokines and reduced mRNA expression levels of HMG-CoA reductase, ACAT, and FXR. The mRNA expression levels of CYP7A1 and LCAT between the HF group and HFCS group were not statistically different. CONCLUSIONS: CS extract supplementation with a high-fat diet improves levels of adipocytokine secretion and glucose homeostasis. CS extract is also effective in decreasing the regulatory pool of hepatic cholesterol, in line with decreased blood and hepatic levels of cholesterol though modulation of mRNA expression levels of HMG-CoA reductase, ACAT, and FXR.

Cytotoxic and ACAT-inhibitory Sesquiterpene Lactones from the Root of Ixeris dentata forma albiflora

  • Ahn, Eun-Mi;Bang, Myun-Ho;Song, Myoung-Chong;Park, Mi-Hyun;Kim, Hwa-Young;Kwon, Byoung-Mog;Baek, Nam-In
    • Archives of Pharmacal Research
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    • 제29권11호
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    • pp.937-941
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    • 2006
  • Ixeris dentata forma albiflora was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and $H_{2}O$. Eight sesquiterpenes were isolated through repeated silica gel and octadecyl silica gel ($C_{18},\;ODS$) column chromatography of the EtOAc and n-BuOH fractions. Physicochemical analysis using NMR, MS and IR revealed the chemical structures of the sesquiterpenes, which were zaluzanin (1), 9a-hydroxyguaian-4(15), 10(14), 11 (13)-triene-6, 12-olide(2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\beta}-hydroxyguaian$-4(15), 10(14)-diene-6, 12-olide (3), $3-O-{\beta}-D-glucopyranosyl-8{\beta}-hydroxyguauan$-10(14)-ene-6, 12-olide (4), ixerin M (5), glucozaluzanin C (6), crepiside I (7), and ixerin D (8). This is the first time that these sesquiterpene lactones have been isolated from this plant. Compounds 1, 2 and 7 revealed relatively high cytotoxicities on human colon carcinoma cell and lung adeno-carcinoma cell, while compounds 5 and 7 showed acyl-CoA: cholesterol acyltransferase (ACAT) inhibitory activity.

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

  • 신윤상;황귀서
    • 대한예방한의학회지
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    • 제18권3호
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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.

식용식물자원으로부터 활성물질의 탐색-IX. 흰씀바귀(Ixeris dentata forma albiflora)뿌리에서 Sesquiterpene Lactone 화합물의 분리 및 구조 동정; ACAT, DGAT 및 FPTase 효소 활성의 저해 (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)

  • 방면호;장태오;송명종;김동현;권병목;김영국;이현선;정인식;김대근;김성훈;박미현;백남인
    • Applied Biological Chemistry
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    • 제47권2호
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    • pp.251-257
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    • 2004
  • 식용식물자원으로부터 활성소재를 찾기 위하여 흰씀바귀 뿌리를 80% MeOH로 추출하고, 얻어진 추출물을 EtOAc, n-BuOH및 $H_2O$로 용매 분획하였다. EtOAc와 n-BuOH 분획에 대하여 column chromatography를 반복하여 4종의 화합물을 분리하였다. 각각에 대하여 2D-NMR을 포함한 스펙트럼 데이터의 해석과 문헌 자료를 조사하여 zaluzanin C (1), $9{\alpha}-hydroxyguaian-4(l5),10(14),11(13)-triene-6,12-olide$ (2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\beta}-hydroxyguaian-4(15),\;10(14 )-diene-6,12-olide$ (3), $3-O-{\beta}- D-glucopyranosyl-8{\beta}hydroxyguaian-10(14)-ene-6,12-olide$ (4)로 구조를 결정하였다. 이들 화합물에 대하여 ACAT(Acyl-CoA: cholesterol acyltransferase), DGAT (diacylglycerol acyltransferase) 및 FPTase(farnesyl-protein transferase)의 활성에 미치는 억제효과를 측정하였다. Compound 1과 Compound 2는 DGAT에 대한 활성억제효과에 있어서 $IC_{50}$ 값이 각각 0.13 mM, 0.10 mM로 나타났고, FPTase에 대하여는 각각 0.15 mM, 0.18 mM로 나타났으며, ACAT에 대하여는 약한 억제 활성을 나타냈다. 따라서 흰씀바귀는 항암 및 항고혈압의 소재 개발에 있어서 유용한 자원으로 활용될 수 있을 것이다.

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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    • 제3권4호
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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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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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    • 제5권5호
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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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    • 제11권1호
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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.

Triterpenoids from the Flower of Campsis grandiflora K. Schum. As Human Acyl-CoA: Cholesterol Acyltransferase Inhibitors

  • Kim, Dong-Hyun;Han, Kyung-Min;Chung, In-Sik;Kim, Dae-Keun;Kim, Sung-Hoon;Kwon, Byoung-Mog;Jeong, Tae-Sook;Park, Mi-Hyun;Ahn, Eun-Mi;Baek, Nam-In
    • Archives of Pharmacal Research
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    • 제28권5호
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    • pp.550-556
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    • 2005
  • The flower of Campsis grandiflora K. Schum. Was extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and H$_2$O. From the EtO Ac fraction, seven triterpenoids were isolated through the repeated silica gel, ODS column chromatographies and preparative HPLC. From the result of physico- chemical data including NMR, MS and IR, the chemical structures of the compounds were determined as 3${\beta}$-hydroxyolean-12-en-28-oic acid (oleanolic acid, 1), 3${\beta}$-hydroxyurs-12-en-28-oic acid (ursolic acid, 2), 3${\beta}$-hydroxyurs-12-en-28-al (ursolic aldehyde, 3), 2${\alpha}$,3${\beta}$-dihydroxyolean-12-en-28-oic acid (maslinic acid, 4), 2${\alpha}$,3${\beta}$-dihydroxyurs-12-en-28-oic acid (corosolic acid, 5), 3${\beta}$,23-dihydroxyurs-12- en-28-oic acid (23-hydroxyursolic acid ,6) and 2${\alpha}$,3${\beta}$,23-trihydroxyolean-12-en-28- oic acid (arjunolic acid, 7). These teriterpenoids were isolated for the first time from this plant. Also, compounds 4, 5, 6, and 7 revealed relatively high hACAT-1 inhibitory activity with the value of 46.2${\pm}$1.1, 46.7${\pm}$0.9, 41.5${\pm}$1.3 and 60.8${\pm}$1.1% at the concentration of 100${\mu}$g/mL, respectively.

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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    • 제8권6호
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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.

A Putative Histone Deacetylase Modulates the Biosynthesis of Pestalotiollide B and Conidiation in Pestalotiopsis microspora

  • Niu, Xueliang;Hao, Xiaoran;Hong, Zhangyong;Chen, Longfei;Yu, Xi;Zhu, Xudong
    • Journal of Microbiology and Biotechnology
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    • 제25권5호
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    • pp.579-588
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    • 2015
  • Fungi of the genus Pestalotiopsis have drawn attention for their capability to produce an array of bioactive secondary metabolites that have potential for drug development. Here, we report the determination of a polyketide derivative compound, pestalotiollide B, in the culture of the saprophytic fungus Pestalotiopsis microspora NK17. Structural information acquired by analyses with a set of spectroscopic and chromatographic techniques suggests that pestalotiollide B has the same skeleton as the penicillide derivatives, dibenzodioxocinones, which are inhibitors of cholesterol ester transfer protein (CETP), and as purpactins A and C', inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). Strain NK17 can make a fairly high yield of pestalotiollide B (i.e., up to 7.22 mg/l) in a constitutive manner in liquid culture. Moreover, we found that a putative histone deacetylase gene, designated as hid1, played a role in the biosynthesis of pestalotiollide B. In the hid1 null mutant, the yield of pestalotiollide B increased approximately 2-fold to 15.90 mg/l. In contrast, deletion of gene hid1 led to a dramatic decrease of conidia production of the fungus. These results suggest that hid1 is a modulator, concerting secondary metabolism and development such as conidiation in P. microspora. Our work may help with the investigation into the biosynthesis of pestalotiollide B and the development for new CETP and ACAT inhibitors.