• 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.

• 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.

• 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.

• 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.

• 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 $100\;{\mu}g/mL$.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.3
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• pp.91-98
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• 2008

80% MeOH extract of black rices fractionated with n-hexane, EtOAc, and n-BuOH. Copper-induced LDL oxidation inhibition assay and ACAT inhibition assay examined with fractions. n-Hexane and EtOAc fractions showed high inhibition activity. We divided n-hexane fraction into three sub-layers(H1 - H3) and EtOAc into eight sub-layers(E1 - E8). H1, H2, E6, and E7 are showed higher inhibition activity than standard in Lp-PLA2 inhibition assay and H1 and E6 are showed higher ACAT inhibition activity than standard.

• 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.

• Applied Biological Chemistry
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• v.51 no.1
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• pp.65-69
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• 2008

The roots of Brassica campestris ssp rapa were extracted with 80% aqueous MeOH, and the concentrated extract was partitioned with EtOAc, n-BuOH and $H_2O$. From the EtOAc fraction, three compounds were isolated through the repeated silica gel and octadecyl silica gel (ODS) column chromatography. From the results of spectroscopic data including NMR and MS, the chemical structures of the compounds were determined as caulilexin C (1), indoleacetonitrile (2) and arvelexin (3). The arvelexin (3) has been isolated from this plant for the first time. Compounds 1, 2 and 3 showed inhibitory activity on human Acyl CoA: cholesterol. transferase 1 (hACAT1) by $54.6{\pm}6.0%$, $69.2{\pm}4.7%$ and $68.6{\pm}3.7%$, and on human Acyl CoA: cholesterol transferase 2(hACAT2) by $4.8{\pm}13.4%$, $45.6{\pm}4.8%$ and $39.5{\pm}4.3%$, respectively, at 100 ${\mu}g/ml$.

• 한국약용작물학회:학술대회논문집
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• 2008.05a
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• pp.269-270
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• 2008

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.67-67
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• 1995

Acyl-CoA:cholesterol acyltransferase (ACAT, EC 2.3.1.26) plays an important role in the control of intracellular free cholesterol content via its cholesterol esterifying activity. ACAT inhibitors are expected to be effective for treatment of atherosclerosis and hypercholesterolemia. In the course of a screening program for ACAT inhibitors from microbial sources, GERI-BP001 M, A, and B were isolated from the fermentation broth of a fungal strain. GERI-BP001 compounds were isolated from a culture broth of Aspergillus fumigatus F37 by acetone extraction, EtOAc extraction, SiO$_2$ column chromatography, and reverse phase HPLC. The structure of GERI-BP001 coumpounds were determined by $^1$H-NMR, $\^$l3/C-NMR, 2D-NMR, NOESY, and long range C-H COSY experiments. GERI-BP001 M, A, and B inhibit ACAT activity in an enzyme assay system using rat liver microsomes by 50% at concentrations of 75, 147, and 71 ${\mu}$M, respectively.