• 한국식품영양과학회지
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• 제28권4호
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• pp.958-962
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• 1999

Hydroxy methylglutaryl CoA(HMG CoA) reductase and acyl CoA:cholesterol acyltransferase(ACAT) are two important enzymes that are associated with regulation of cholesterol metabolism. The inhibitors of HMG CoA reductase and ACAT are very effective in lowering serum cholesterol in most animal species. In present study, various plant extracts with hot water were used to examine the inhibitory activities against HMG CoA reductase and ACAT that are involved in cholesterol biosynthesis and cholesterol esterification in tissues, respectively. The extracts of Fagophyrum rotundatum, Rosa multiflora, Rosa rugosa and Alisma orientalis exhibited significant inhibitory activities against the ACAT, 29%, 24%, 19%, and 18%, respectively. However the extracts of Typha augustifolia, Polygonum cuspidatum, Crataegus pinnatifida, Polygonum multiflorum inhibited the HMG CoA reductase activity by 53%, 42%, 37%, and 33% respectively. Results suggest that these plant extracts might play important roles in the regulation of the cholesterol metabolism in vivo.

• 한국식품영양과학회지
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• 제23권3호
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• pp.371-379
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• 1994

The effect of milk in low and high cholesterol diets were investigated on serum cholesterol esterification. Weanling male Sprague-Dawley rats were divided into low(0.01% w/w) and high (1.01% w/w) cholesterol-diets groups. Bothlow and high cholesterol groups were consisted of three groups : control , LM(low heat milk), and HM (high heat milk) groups. After feeding these experimental diets for six weeks, serum cholesterol (free cholesterol and cholestryl ester) concentration and activity of lecithin.: cholesterol acyltransferase (LCAT) were measured, and serum lipoprotein profile was examined using gel column chromatography. According to the result, activity of LCAT was elevated independently by intakes of high cholesterol and milk , which resulted in the increase of daily turnover of serum cholesteryl ester. However, the turnover of HDL-cholesteryl ester increased only by milk. LCAT activity was moderately correlated with levels of total-and HDL-free choelsterol. It is concluded from the present study that milk had the cholesterol-lowering effect which partly appears to be mediated through facilitated reverse cholesterol transport.

• Journal of Ginseng Research
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• 제19권3호
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• pp.212-218
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• 1995

A human hepatoma cell line, hep G2, was used to investigate the mechanism of serum cholesterol reduction by ginseng total saponin, ginsenoside-$Rb_1$, - $Rb_2$, and non-saponin fraction (ether extraction). Hep G2 cells were incubated in 10 $\mu\textrm{g}$/ml of cholesterol containing serum free-RPMl1640 medium with various concentration of ginseng components. The amounts of cholesterol in Hep G2 cells were decreased to maximum 51% in total saponin or two ginsenoside-treated groups while there was 137% increase in cholesterol level of control group as compared with that of normal group. Nonsaponin groups did not show the same effect. In order to elucidate the observed changes in the amount of cholesterol, the activity of amyl CoA : cholesterol acyltransferase (ACAT) in groups showing remarkable reduction in cholesterol amount, i.e., total saponin 10-6%, ginsenoside-$Rb_1$ $10^{-4}$%, ginsenoside-$Rb_2$, $10^{-4}$%, and non-saponin fraction $10^{-4}$%, was assayed using [1-$^{-14}C$%]oleic acid as enzyme substrate. The activity of ACAT was increased in all groups tested as compared with that of control group except for non-saponin group cultured in water soluble cholesterol containing medium. The serum cholesterol lowering effects of ginseng components can partially be attributed to the increased hepatocellular ACAT activity.

• 농업과학연구
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• 제41권1호
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• pp.47-58
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• 2014

The effect of conjugated linoleic acid (CLA) isomers esterified in diacylglycerol (DAG)-rich oil on lipid metabolism was investigated. Since dietary DAG has been known to induce the regression of atherosclerosis, CLA-DAG and olive-DAG oils containing similar levels of DAG (51.4~54.2%) were synthesized from olive oil. Hyperlipidemic C57BL/6J mice were then fed high-fat high-cholesterol diets supplemented with these oils (5% each) for 7 wk. The CLA-DAG diet containing 2.1% CLA isomers (0.78% c9,t11-CLA; 1.18% t10,c12-CLA) remarkably increased the levels of total plasma cholesterol and glutamic oxaloacetic transaminase (GOT) along with hepatic cholesterol and triacylglycerol (TAG) contents. Furthermore, the CLA-DAG diet inhibited fat uptake into adipose tissue whereas fat deposition (especially in the liver) was increased, resulting in the development of fatty livers. Hepatic fatty acid composition in the CLA-DAG mice was different from that of the olive-DAG mice, showing higher ratios of C16:1/C16:0 and C18:1/C18:0 in the liver. The activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT) was higher in CLA-DAG mice while plasma lecithin:cholesterol acyltransferase (LCAT) activity and the ferric reducing ability of plasma (FRAP) were lower in CLA-DAG mice compared to the olive-DAG animals. Results of the present study suggest that CLA incorporation into DAG oil could induce atherosclerosis in mice.

• Natural Product Sciences
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• 제15권2호
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• pp.110-113
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• 2009

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays important roles in intestinal absorption of cholesterol, hepatic production of lipoproteins and accumulation of cholesteryl ester within macrophages and smooth muscle cells. In our study, eight polyacetylenes (1 - 8), were isolated from the roots of Gymnaster koraiensis, and their chemical structures were identified on the basis of spectroscopic analysis and mass. Compound 2 with the (10S)-15,16-epoxy group in skeleton strongly inhibited ACAT enzyme with $IC_{50}$ value of 35.8 ${\mu}g$/mL, meanwhile the other compounds displayed significant inhibition of ACAT enzyme with the $IC_{50}$ values from 45.5 to 55.1 ${\mu}g$/mL.

• Archives of Pharmacal Research
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• 제26권9호
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• pp.716-718
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• 2003

In the course of our search for Acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors from natural sources, a new type of ACAT inhibitor was isolated from a methanol extract of Diospyros kaki. On the basis of spectral and structural evidence, the compound was identified as pheophorbide A-methyl ester. Pheophorbide A-methyl ester inhibited ACAT activity in a dose dependent manner with an $IC_{50}$ value of 1.85 $\mu$ g/mL.

• Journal of Microbiology and Biotechnology
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• 제18권10호
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• pp.1663-1665
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• 2008

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays an important role in the intestinal absorption of cholesterol, hepatic production of lipoproteins, and accumulation of cholesteryl ester within cells. During the course of screening to find ACAT inhibitors from microbial sources, the present authors isolated pyripyropene A from Penicillium griseofulvum F1959. Pyripyropene A, an ACAT2-specific inhibitor, has already been produced from Aspergillus fumigatus. Yet, Aspergillus fumigatus is a pathogen and only produces a limited amount of pyripyropene A, making the isolation of pyripyropene A troublesome. In contrast, Penicillium griseofulvum F1959 was found to produce approximately 28 times more pyripyropene A than Aspergillus fumigatus, plus this report also describes the ideal conditions for the production of pyripyropene A by Penicillium griseofulvum F1959 and its subsequent purification.

• 생약학회지
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• 제30권4호
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• pp.384-396
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• 1999

Acyl-CoA: Cholesterol Acyltransferase (ACAT) is a key enzyme responsible for cholesteryl ester formation in atherogenesis and in cholesterol absorption from the intestines. In addition under pathological conditions, formation and accumulation of cholesteryl ester as lipid droplets by ACAT within macrophages constitute a characteristic feature of early lesions of atherosclerotic plaques. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. ACAT inhibitors of natural origin have been rarely reported. In our screening program for ACAT inhibitors, 303 plants were extracted with methanol or ethanol, and screened for the inhibitory activity against ACAT from the rat liver microsome. Extracts of 13 plants including Quercus aliena, Diospyros kaki, Platycarya strobilacea and Hibiscus syriacus inhibited more than 90% of ACAT activity and 43 samples in alcohol extracts such as Magnolia obovata and Panax ginseng also inhibited more than 70% of ACAT activity at a concentration of $100\;{\mu}g/ml$.

• 한국식품과학회지
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• 제32권1호
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• pp.200-205
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• 2000

췌장에서 분비되는 cholesterol esterase(CEase)와 소장의 acyl coenzyme A: cholesterol acyltransferase(ACAT)는 흡수된 콜레스테롤을 다시 ester화하는데 관여한다. 한방재료 중 건위, 진토 및 수렴지사작용 등을 가지는 초두구(Alpiniae Katusumadaii Semen)의 에탄올 추출물이 in vitro에서 cholesterol esterase활성에 대하여 강한 저해작용을 보였으며 에탄올추출물의 용매분획 중 클로로포름분획이 다른 분획들, 즉 에틸 아세테이트분획, 부탄올분획 및 물 분획보다 강하였다. 초두구의 클로로포름분획이 고 콜레스테롤식이를 섭취시킨 rat에서 혈중 콜레스테롤치를 저하시키는 효과가 있는지 측정한 실험에서 chloroform분획을 100 mg/kg 및 150 mg/kg 섭취시켰을 경우 각각 총cholesterol 함량이 11.8% 및 20.8% 감소하였으며 HDL-cholesterol 함량 및 동맥경화지수는 정상군에 가깝게 회복된 것으로 나타났다. 또한 초두구 chloroform분획의 독성검사 결과 mouse에서 $LD_{50}$은 1,625mg/kg으로 산출되었다.

• 생명과학회지
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• 제12권1호
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• pp.106-112
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• 2002

췌장에서 분비되는 콜레스테롤 에스터레이즈(pCEase)와 소장의 acyl coenzyme A:cholesterol acyltransferase (ACAT)는 흡수된 콜레스테롤을 다시 ester화하는데 관여한다. 한방재료 중 순환촉진작용 및 건위작용 등을 가지는 계피(Cinnamomi cortex)의 에탄올 추출물이 in vitro에서 pCEase 활성에 대하여 강한 저해작용을 보였으며 에탄올 추출물의 용매분획 중 클로로포름분획이 다른 분획들, 즉 에틸 아세테이트분획, 부탄올분획 및 물 분획보다 저해활성이 강하였다. 계피의 클로로포름분획이 고콜레스테롤식 이를 섭취시킨 rat에서 혈중 콜레스테롤치를 저하시키는 효과가 있는지 측정한 실험에서 클로로포름분획을 150 mg/kg 섭취시켰을 경우 고콜레스테롤식이만은 투여한 대조군에 비하여 총cholesterol 함량이 25.1% 감소하였으며, HDL-cholesterol 함량도 33.4$\pm$1.82 g/dl로 정상군 수준으로 회복되었고 동맥경화지수 역시 현저하게 감소된 것으로 나타났다. 콜레스테롤 생합성에 관여하는 효소인 HMG-CoA reductase 활성을 측정한 결과, 고콜레스테롤 식이에 의해 감소되었던 활성이 계피 클로로포름분획의 투여량을 증가시킬수록 증가하였으나 150 mg/kg 투여군 에서도 정상군에 비하여 유의적인 감소를 보였다. 또한 계피 클로로포름분획의 독성검사 결과, mouse에서 LD$_{50}$ 은 1,300 mg/kg으로 산출되었다.