• Title/Summary/Keyword: ACAT-1

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Screening for Human ACAT-1 and ACAT-2 Inhibitory Activity of Edible Plant Extracts (식물추출물의 Human-ACAT 저해활성 검색)

  • Lee, Dae-Young;Jeong, Tae-Sook;Lyu, Ha-Na;Bang, Myun-Ho;Hong, Yoon-Hee;Lee, Youn-Hyung;Baek, Nam-In
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.5
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    • pp.341-348
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    • 2008
  • Cholesterol acyltransferase (ACAT) catalyzes the acylation of cholesterol to cholesteryl ester with long chain fatty acids and ACAT inhibition is a useful strategy for treating hypercholesterolemia or atherosclerosis. Inhibitory effects on ACAT of the MeOH extracts prepared from 163 edible plants were evaluated. 15 species out of 163 species exhibited higher than 50% of inhibition on the hACAT-1 and 9 species exhibited higher than 50% of inhibition on the hACAT-2 activity at their concentration of $100\;{\mu}g/mL$.

Human Acyl-CoA: Cholesterol Acyltransferase (hACAT) Inhibitory Activities of Triterpenoids from Roots of Glycine max (L.) Merr

  • Lee, Jin-Hwan;Ryu, Young-Bae;Lee, Byong-Won;Kim, Jin-Hyo;Lee, Woo-Song;Park, Yong-Dae;Jeong, Tae-Sook;Park, Ki-Hun
    • Bulletin of the Korean Chemical Society
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    • v.29 no.3
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    • pp.615-619
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    • 2008
  • Eight triterpenoids, six lanostanes 1-6, one lupenane 7, and one oleanane 8, were isolated by bioactivity-guided fractionation of the ethylacetate extract from roots of Glycine max (L.) Merr. All isolated compounds were examined for their inhibitory activities against human ACAT-1 (hACAT-1) and human ACAT-2 (hACAT-2). Among them, three triterpenoids showed potent hACAT inhibitory activities, (24R)-ethylcholest-5-ene-3,7-diol (1) and 3b -hydroxylup-20(29)-en-28-oic acid (7) exhibited more potent inhibitory activity against hACAT-1 (1: IC50 = 25.0 1.2 and 7: IC50 = 11.5 0.4 m M) than hACAT-2 (1: IC50 = 102.0 5.4 and 7: IC50 = 33.9 3.7 m M), respectively. Interestingly, 5a ,8a -epidioxy-24(R)-methylcholesta-6,22-diene-3b -ol (4) has proven to be a specific inhibitor against hACAT-1 (IC50 = 38.7 0.8 m M) compared to hACAT-2 (IC50 >200). In conclusion, this is the first study to demonstrate that triterpenoids of G. max have potent inhibitory activities against hACAT-1 and hACAT-2.

Screening of Microorganisms Having ACAT Inhibitor Activity from Soil and Characterization of AI-3, ACAT Inhibitor Produced by Streptomyces sp. A-3 (토양으로부터 ACAT 저해활성을 나타내는 미생물의 탐색과 방선균이 생산하는 ACAT 저해물질, AI-3의 특성)

  • 정태숙;김성욱;이항우;손광희;권용욱;최명언;복성해
    • Microbiology and Biotechnology Letters
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    • v.21 no.6
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    • pp.600-608
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    • 1993
  • About 1, 300 strains isolated from soil were evaluated for acyl-CoA:cholesterol acyltransferase (ACAT) inhibition activity. About 4.0% of actinomycetes and 3.6% of fungi showed greater than 50% inhibition activity, respectively. However, none of the isolated bacteria exhibited inhibition activity more than 50%. Among them, one Streptomyces sp. A-3 showed a higher ACAT inhibition activity in culture broth. Isolation of the ACAT inhibitor (AI-3) was achieved by Amberlite XAD-7 column, silica-gel column, Sephadex LH-20 gel-filtration and reverse phase HPLC.

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ACAT (Acyl-CoA:cholesterol Acyltransferase) Inhibitory Effect and Quantification of Pyranocurmarin in Different Parts of Angelica gigas Nakai (참당귀(Angelica gigas)에서 분리한 pyranocurmarin 성분의 ACAT 저해활성 및 참당귀 부위별 pyranocurmarin 성분의 함량 분석)

  • Kim, Geum-Soog;Park, Chun-Geun;Jeong, Tae-Sook;Cha, Seon-Woo;Baek, Nam-In;Song, Kyung-Sik
    • Journal of Applied Biological Chemistry
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    • v.52 no.4
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    • pp.187-194
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    • 2009
  • Two pyranocoumarin constituents have been isolated from Angelica gigas and were identified as decursinol angelate (1) and decursin (2) by means of NMR analysis, respectively. Human acyl-CoA:cholesterol acyltransferase (hACAT) inhibitory activity of decursinol angelate (1) and decursin (2) was evaluated. Decursin (2) showed significantly inhibitory activity against hACAT1 and hACAT2 with $IC_{50}$ value of 137 and $168\;{\mu}M$, respectively, whereas decursinol angelate (1) exhibited weak ACAT inhibitory activity. These results suggested that decusin from A. gigas might be effective for the prevention and the treatment of hypercholesterolemia or atherosclerosis by inhibitory effect on hACAT. The contents of decursinol angelate (1) and decursin (2) were analyzed in various parts of A. gigas including flower, seed, leaf and root using LC/MS/MS (ESI, positive ion mode, MRM mode). The content of decursinol angelate was increased in order of flower, seed, leaf, and root and decursin content was increased in order of flower, seed, leaf, and root. It was expected that unused parts including leaf and flower of A. gigas might be useful as new functional sources by their high contents of decursin and decursinol angelate.

Acyl-CoA: Cholesterol Acyltransferase Inhibitors from llex macropoda

  • Im Kyung-Ran;Jeong Tae-Sook;Kwon Byoung-Mog;Baek Nam-In;Kim Sung-Hoon;Kim Dae-Keun
    • Archives of Pharmacal Research
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    • v.29 no.3
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    • pp.191-194
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    • 2006
  • Twigs from llex macropoda were extracted with MeOH, and the concentrated extracts were partitioned with $CH_2Cl_2$, EtOAc, n-BuOH, and $H_2O$. Repeated column chromatography of the $CH_2Cl_2$ fraction ultimately resulted in the isolation of two compounds, via activity-guided fractionation, using ACAT inhibitory activity measurements. According to the physico-chemical data, the chemical structures of these isolated compounds were identified as lupeol (1) and betulin (2). Compounds 1 and 2 were shown to inhibit the activity of hACAT-1 and hACAT-2 in a dose-dependent manner, and compounds 1 and 2 inhibited hACAT-1 with $IC_{50}$ values of 48 and $83{\mu}M$, respectively.

Nicorandil alleviated cardiac hypoxia/reoxygenation-induced cytotoxicity via upregulating ketone body metabolism and ACAT1 activity

  • Bai, Yan Ping;Han, Lei Sen
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.1
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    • pp.37-45
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    • 2019
  • To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly ${\beta}$-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other $K_{ATP}$ channel openers.

ACAT inhibitory effect of Guineensine isolated from Piper longum L.

  • Lee, Seung-Woong;Kim , Koan-Hoi;Kim, Young-Ho;Rho, Mun-Chual;Lee, Hyun-Sun;Kim, Young-Kook
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.201.1-201.1
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    • 2003
  • Study of Acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors from medicinal plants, we found strong inhibitory activity of ACAT enzyme from rat liver microsome by the CHC1$_3$ extract of Piper longum. Bioactivity-guided fractionation led to the isolation of Guineensine (1), its structure was elucidated by spectroscopic (IR, UV, MS and NMR) means. It inhibited ACAT activity in a dose-dependent manner with IC$\sub$50/ values of 1.2 $\mu\textrm{g}$/ml on in vitro assay using rat liver microsome.

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Inhibition of Low Density Lipoprotein-oxidation, ACAT-1, and ACAT-2 by Lignans from the Bark of Machilus thunbergii

  • Shrestha, Sabina;Park, Ji-Hae;Lee, Dae-Young;Cho, Jin-Gyeong;Lee, Do-Gyeong;Cho, Moon-Hee;Jeong, Tae-Sook;Kang, Hee-Cheol;Baek, Nam-In
    • Journal of Applied Biological Chemistry
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    • v.54 no.1
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    • pp.63-66
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    • 2011
  • The bark of Machilus thunbergii was extracted with 80% aqueous methanol (MeOH), and the concentrated extract was partitioned using ethyl acetate (EtOAc), butanol (n-BuOH), and $H_2O$, successively. From the EtOAc fraction, five lignans were isolated through the repeated silica gel, octadecyl silica gel (ODS) and, Sephadex LH-20 column chromatography. Based on nuclear magnetic resonance (NMR), mass spectroscopy (MS), and infrared spectroscopy (IR) spectroscopic data, the chemical structures of the compounds were determined to be machilin A (1), machilin F (2), licarin A (3), nectandrin A (4), and nectandrin B, (5). This study presents comparative account of five lignans from M. thunbergii bark contributing inhibition of low density lipoprotein (LDL), ACAT-1, and ACAT-2. Compounds 2-5 showed varied degree of antioxidant activity on LDL with $IC_{50}$ values of 2.1, 11.8, 15.3, and $4.1{\mu}M$. Compounds 1, 2, and 3 showed inhibition activity on ACAT-1 with values $63.4{\pm}6.9%$ ($IC_{50}=66.8{\mu}M$), $53.7{\pm}0.9%$ ($IC_{50}=109.2{\mu}M$), and $78.7{\pm}0.2%$ ($IC_{50}=40.6{\mu}M$), respectively, at a concentration of 50 mg/mL, and on ACAT-2 with values $47.3{\pm}1.5%$ ($IC_{50}=149.7{\mu}M$), $39.2{\pm}0.2%$ ($IC_{50}=165.2{\mu}M$), and $52.1{\pm}1.0%$ ($IC_{50}=131.0{\mu}M$, respectively, at a concentration of 50 mg/mL.

Human Acyl-CoA: Cholesterol Acyltransferase Inhibitory Effect of Flavonoids from Roots of Glycine max (L.) Merr

  • Lee, Jin-Hwan;Seo, Woo-Duck;Jeong, Seong-Hun;Jeong, Tae-Sook;Lee, Woo-Song;Park, Ki-Hun
    • Journal of Applied Biological Chemistry
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    • v.49 no.2
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    • pp.57-61
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    • 2006
  • Isoflavones 1-3 and pterocarpans 4-8 were isolated from methanol extract of roots of Glycine max. In inhibitory effect against human acyl-CoA:cholesterol acytransferase (ACAT)-1 and ACAT-2, glyceollin I 5 showed potent hACAT-1 ($IC_{50}=299.0{\mu}M$) and hACAT-2 ($IC_{50}=82.7{\mu}M$) inhibitory activities.

ACAT Inhibition of Polyactylenes from Gymnaster koraiensis

  • Jung, Hyun-Ju;Hung, Tran-Manh;Na, Min-Kyun;Min, Byung-Sun;Kwon, Byoung-Mog;Bae, Ki-Hwan
    • Natural Product Sciences
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    • v.15 no.2
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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.