• Archives of Pharmacal Research
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• 제29권3호
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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.

• 한국약용작물학회지
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• 제16권5호
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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 Applied Biological Chemistry
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• 제52권4호
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• pp.187-194
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• 2009

참당귀 뿌리로부터 2종의 pyranocoumarin 성분을 분리하고 그들의 구조는 NMR 분석에 의해 각각 decursinol angelate(1), decursin(2)로 결정하였다. 이들 화합물에 대하여 hACAT 저해활성을 검정해본 결과, decursinol angelate(1)가 약한 저해활성을 나타낸 반면 decursin(2)은 hACAT1와 hACAT2에 대하여 $IC_{50}$ 값이 각각 137, $168\;{\mu}M$로서 우수한 저해활성을 나타내었다. 한편, 참당귀의 뿌리를 비롯한 꽃, 종자, 잎 등 여러부위에서 decursinol angelate(1), decursin(2)를 정량분석하였는데, 이때 LC/MS/MS(ESI, positive ion mode, MRM mode) 분석을 이용하였다. Decursinol angelate의 함량은 뿌리>잎>종자>꽃 순으로 높았으며, decursin의 함량은 뿌리>종자>꽃>잎 순으로 높게 측정되었다. 이상의 결과들은, 참당귀의 decursin이 동맥경화와 같은 심혈관 질환의 개선과 치료를 위해 유용하게 이용될 수 있음을 시사하였다. 또한 뿌리 이외에 그 동안 이용되지 않고 있던 참당귀 꽃, 잎과 같은 비상용부위에도 기능성물질인 decursin, decursinol angelate이 상당량 함유되어 있음이 구명되어 이러한 부위도 새로운 천연 기능성 소재로서 활용될 수 있음을 기대할 수 있었다.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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.

• 한국환경과학회지
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• 제26권11호
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• pp.1275-1284
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• 2017

Acyltransferase (AT) catalyzes the transfer of an acyl moiety from acyl-coenzyme A (acyl-CoA) to an acceptor. ATs play important roles in the maintenance of homeostasis in the human body and have been linked to various diseases; therefore, several ATs have been proposed as potential targets for the treatment or prevention of such diseases. The AT family includes acyl-CoA:cholesterol AT (ACAT), diacylglycerol AT, and monoacylglycerol AT for the metabolism of lipids. Furthermore, recent molecular biological studies revealed the existence of their isozymes with distinct functions in the body. ACAT plays a critical role in the formation of cholesteryl esters from cholesterol and fatty acids, and is a potential target for treating hypercholesterolemia. During an experiment designed to discover biologically active compounds from herbal medicines, we isolated two known guaianolide sesquiterpene lactones from Chrysanthemum boreale Makino (Compositae). The lactones were characterized from their spectroscopic data (NMR, IR, MASS). These compounds were subjected to ACAT inhibition assay. Here, we report the isolation and structural elucidation of the compounds 8-o-acetyl-2-methoxy-10-hydroxy-3,11(13)-guaiadiene-12,6-olide and 8-acetyl-3,10-hydroxy-4(15),11(13)-guaiadiene-12,6-olide. In the ACAT inhibition assay, compound 1 showed strong inhibitory activity, with an $IC_{50}$ value $45{\mu}g/mL$, whereas compound 2 did not exhibit significant inhibitory activity with an over $100{\mu}g/mL$.

• 생약학회지
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• 제30권1호
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• pp.74-78
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• 1999

Nine sesquiterpene lactones, which were isolated from Hemisteptia lyrata Bunge, Chrysanthemum zawadskii Herbich var. latilobum Kitamura and Chrysanthemum boreale Makino were evaluated for the inhibition upon the nitric oxide release from the Raw cell and for the ACAT (acyl Co A: cholesterol acyltransferase) inhibitory assay. In the nitric oxide release inhibitory experiment, hemistepsin B $(IC_{50}\;=\;0.05\;{\mu}g/ml,\;0.15\;{\mu}M),$ cumambrin B, tulipinolide and costunolide exhibited strong inhibition with $IC_{50}$ values $0.05\;{\mu}g/ml\;(0.15\;{\mu}M),\;0.1\;{\mu}g/ml\;(0.38\;{\mu}M),\;0.2\;{\mu}g/ml\;(0.69\;{\mu}M)$ and $0.2\;{\mu}g/ml(0.86\;{\mu}M),$ respectively. In the ACAT inhibitory assay, angeloylcumambrin B, tigloylcumambrin B, tulipinolide and costunolide exhibited strong inhibition with $IC_{50}$ values $33\;{\mu}g/ml\;(95.4\;{\mu}M),\;22\;{\mu}g/ml\;(63.6\;{\mu}M),\;38\;{\mu}g/ml\;(151\;{\mu}M)$ and $17\;{\mu}g/ml(73.3\;{\mu}M),$ respectively, whereas other compounds did not exhibit significant activity against ACAT above $100\; {\mu}g/ml.$.

• Bulletin of the Korean Chemical Society
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• 제30권5호
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• pp.1088-1092
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• 2009

A series of 2-alkyl or 2-arylthio-5,8-dimethoxy-1,4-naphthoquinones (2-Thio-DMNQ, 5a-s) and 2-alkylamino-5,8- dimethoxy-1,4-naphthoquinones (2-Amino-DMNQ, 6a-k) was synthesized and evaluated for their ACAT inhibitory activities. Among them, the 2-dodecylthio-DMNQ 5l and 2-isobutylamidoundodecylthio-DMNQ 5r showed the most potent ACAT inhibitory activities with $IC_{50}$ value of 22.8 and 24.4 ${\mu}M$, respectively. In a structure-activity relationship study, 2-thio-DMNQs with side chains of carbon number 11 $\sim$ 15 exhibited significant ACAT inhibitory activities.

• Bulletin of the Korean Chemical Society
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• 제29권3호
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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.

• 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 $100\;{\mu}g/ml$.