• Journal of Life Science
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• v.28 no.2
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• pp.247-256
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• 2018

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.

• Journal of Korean Society of Environmental Engineers
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• v.39 no.3
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• pp.124-131
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• 2017

In this study, We investigated the effects of water temperature and empty bed contact time (EBCT) on the biodegradability of 8 blood lipid lower agents (BLLAs) in biological activated carbon (BAC) process. Experiments were conducted at three water temperatures ($8^{\circ}C$, $16^{\circ}C$ and $24^{\circ}C$) and three EBCTs (5 min, 10 min and 15 min). Increasing water temperature and EBCT increased the biodegradation efficiency of BLLAs in BAC process. Simvastatin and fenofibrate were the highest biodegradation efficiency, but atorvastatin and clofibric acid were the lowest. The kinetic analysis suggested a pseudo-first-order reaction model for biodegradation of 8 BLLAs at various water temperatures and EBCTs. The pseudo-first-order biodegradation rate constants ($k_{bio}$) of clofibric acid and atorvastatin were $0.0075min^{-1}$ and $0.0122min^{-1}$ at $8^{\circ}C$, and were $0.0540min^{-1}$ and $0.0866min^{-1}$ at $24^{\circ}C$, respectively. By increasing the water temperature from $8^{\circ}C$ to $24^{\circ}C$, the biodegradation rate constants ($k_{bio}$) were increased 7.1~7.2 times.

• Journal of Hospice and Palliative Care
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• v.13 no.1
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• pp.7-12
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• 2010

Purpose: To evaluate medications at the end of life care for terminal cancer patients during their last admission. Methods: Medical records of terminal cancer patients during their last admission from July 2003 to April 2008 at a district academic hospital were evaluated. Patient's characteristics, therapeutic drug classification during their last admission and on the patient's day of death, and the administrated route and number of medications on the patient's day of death were analyzed. Results: Total 81 patients were included. The median patient age was 63 years. The median length of admission was 18 days (range: 1~101). 54% of the patients had more than one comorbidities. The most frequently prescribed drugs during the last admission were opioid analgesics (63%), followed by antibiotics (58%) and antacids (53%). On the day of death, common medications were antibiotics (59%), antacids (58%), and opioid analgesics (46%). Intravenous injection was given to 81% of the patients and intramuscular injection was given to 16% of the patients on the day of patient's death. Number of medications prescribed to patients was between 0 and 11 (median: 3) and 12% (10/81) of the patients took over 8 medications including intravenous and oral drugs on the day of death. 6% (5/81) of the patients took potentially futile medications, like multivitamin or statin until the day of death. Conclusion: This study suggests that potentially futile medications and uncomfortable care were given to terminal cancer patients. Multicenter-based studies are necessary to diminish futile medications by essential medication at the end of life care for terminal cancer patients.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.59 no.2
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• pp.167-173
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• 2014

Red yeast rice (RYR) is the product of fermented yeast by Monascus strains on rice, and has recently become a popular dietary supplement as a traditional food in Asia. RYR contains monacolin K substances known to inhibit cholesterol synthesis as efficiently as statin drugs. To determine the optimal rice cultivar for manufacturing RYR, 7 rice cultivars (Goami, Goami2, Sangjuchalbyeo, Seolgaeng, Saegyejinmi, Yeonghojinmi and Chilbo) were fermented using two Monascus strains (M. ruber KCTC6122 and KCCM60141 of M. ruber) in this study. The monacolin K content of Sangjuchalbyeo were 47.24 ppm on KCTC6122 cultures and 117.03 ppm on KCCM60141 cultures, respectively. Other cultivars, especially Goami and Goami2, which had less content of monacolin K could not seem to ferment normally because those didn't show red color. These results imply that Sangjuchalbyeo can be optimal rice cultivar as a commercial RYR which is well fermented rice and has high content of monacolin K.

• Journal of Life Science
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• v.27 no.3
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• pp.325-333
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• 2017

High level of plasma cholesterol is strongly associated with the development of atherosclerosis and coronary heart disease. Clinical trials designed to reduce plasma cholesterol level by diet or pharmacological intervention have resulted in marked reduction of disease incidence. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which reduces cholesterol biosynthesis in the liver is the key enzyme of the mevalonate pathway that produces cholesterol. In this study, 71 naturally occurring phenolic compounds were tested for inhibitory activities against HMG-CoA reductase. Eleven compounds out of 71 showed inhibitory activities: three hydrolyzable tannin (geraniin, acetonyl geraniin and pentagalloyl ${\beta}-D-glucose$), four benzoic acid derivatives (benzoic acid, trans-cinnamic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid), and four naphthoquinone derivatives (1,2-naphthoquinone, 1,4-naphthoquinone, plumbagin and shikonin). At the concentration of $10{\mu}g/ml$, 1,4-naphthoquinone inhibited HMG-CoA reductase by 99.4%, and then plumbagin 91.4%, pentagalloyl ${\beta}-D-glucose$ 46.6%, 2,4-dihydroxybenzoic acid 40.9%, shikonin 37.7%, 1,2-naphthoquinone 36.6%, trans-cinnamic acid 32.0%, acetonyl geraniin 30.2%, benzoic acid 28.5%, geraniin 28.3% and 2,5-dihydroxybenzoic acid 22.3%, respectively. $IC_{50}$ values of 1,4-naphthoquinone and plumbagin was $2.1{\mu}g/ml$ and $5.8{\mu}g/ml$, respectively.

• KSBB Journal
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• v.24 no.2
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• pp.163-169
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• 2009

Lovastatin (also known as Mevinolin, Mevacor, and Monacolin K), an inhibitor of the HMG-CoA reductase produced by Aspergillus terreus and other fungi, is used to reduce serum cholesterol levels in human beings. It is derived biosynthetically from two polyketides. One of these is a nonaketide that undergoes cyclization at a hexahydronaphthalene ring system, and the other is a simple diketide, 2-methylbutyrate. Two primer pairs were designed based on the amino acid sequences of lovastatin polyketide synthase and lovastatin diketide synthase for the PCR screening of lovastatin-producing strains. Among the seven selected strains, SJ-2 evidenced the highest level of lovastatin production in both liquid and solid cultures. Soybeans with SJ-2 were treated via 1 hour of heat shock at $30^{\circ}C$ for the mass production of lovastatin. The heat-treated soybeans were inoculated on rice bran and the koji extract was obtained after 15 days of incubation. It yielded the highest level of lovastatin production among the strains, and also evidenced 75% inhibition activity against HMG-CoA reductase. We developed an efficient PCR screening method for lovastatin-producing strains, using lovastatin biosynthesis genes.

• The Korea Journal of Herbology
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• v.33 no.5
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• pp.89-103
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• 2018

Objectives : This study is aimed to compare the changes in Antioxidative capacity of Liriopis Tuber by steaming process and to compare the effects in hyperlipidemia induced rats fed high cholesterol diet between Simvastatin and Liriopis Tuber by steaming process. Methods : The SD rats were divided into six groups: normal diet (Nor), high cholesterol diet (Veh), high cholesterol diet plus Simvastatin 5 mg/kg (Sim), high cholesterol diet plus LT0 extract 200 mg/kg (LT0), high cholesterol diet plus LT6 extract 200 mg/kg (LT6) and high cholesterol diet plus LT9 extract 200 mg/kg (LT9). We compared the total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) contents and reactive oxygen species (ROS) from each serums. Protein expression in liver tissues related to antioxidant and cholesterol was analyzed. Results : The Antioxidant activity of Liriopis Tuber increased by steaming process. In vivo, TC, TG, LDL-c, atherogenic index (AI) and cardiac risk factor (CRF) decreased and HDL-c increased with increasing steaming frequency. aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) decreased with increasing steaming frequency. ROS decreased only in LT9, and SOD, catalase and glutathione peroxidase (GPx) increased with increasing steaming frequency. phospho-AMP-activated protein kinase (p-AMPK) increased and sterol regulatory element-binding protein 2 (SREBP-2), Phospho-Acetyl-CoA Carboxylase (p-ACC) and HMG-CoA reductase (HMGCR) decreased with increasing steaming frequency. Liver staining showed a decrease in hepatic fat accumulation of LT9. LT9 showed significant results in all experiments. Conclusions : LT9 showed significance of anti-lipid effect and improved fatty liver of hyperlipemia induced rats fed on high cholesterol diet, In conclusion, LP9 can be effectively used for the treatment of hyperlipidemia.

• Journal of Physiology & Pathology in Korean Medicine
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• v.36 no.5
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• pp.181-186
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• 2022

Atractylodes macrocephala (AM) and Amomum villosum (AV) are the most common herbs in Korean Medicine to treat digestive diseases. In this study, we investigated the cholesterol lowering effects of mixtures of AM and AV extracts on high cholesterol diet (HCD) induced dyslipidemia mouse model. We classified animals into six different groups; Group 1: Normal diet, Group 2: HCD, Group 3: AV extracts : AM extracts (1:1) (200 mg/kg) + HCD, Group 4: AV extracts : AM extracts (1:2) (200 mg/kg) + HCD, Group 5: AV extracts : AM extracts (1:3) (200 mg/kg) + HCD, Group 6: Simvastatin 40 mg/kg + HCD. After 4 weeks of oral administration of respective drugs, we checked body, liver and epididymal fatweights along with liver and serum triacylglyceride (TG) concentration, total and low density lipoprotein (LDL) cholesterol in serum. Moreover, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (HMGCR), LDL receptor (LDLR), and sterol regulatory element-binding protein 2 (SREBP2) were detected by RT PCR or western blot analysis. The overall results showed that mixtures of AM and AV extracts inhibited HCD-induced increases of total cholesterol and LDL cholesterol in serum. Those effects seem to be caused by AM and AV extracts through inhibition of HMGCR expression. And thus blood cholesterol is induced into the liver by increasing LDLR expression, which is regulated by SREBP2 transcrption factor. The cholesterol lowering effects and mechanism of mixtures of AM and AV extracts was similar to the statin. We have identified the potential mixtures of AM and AV extracts as a new treatment for dyslipidemia.

• Analytical Science and Technology
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• v.22 no.5
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• pp.407-414
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• 2009

A simultaneous determination method for cholesterol, lanosterol and desmosterol was developed using gas chromatography/mass spectrometry. Urine was enzymatically hydrolyzed with ${\beta}$-glucuronidase/arylsulfatase. Samples were prepared using extractions with a mixture of ethyl acetate-hexane (2:3, v/v), followed by derivatization with a mixture of MSTFA/TMSI/TMCS (100:2:5 v/v/v). All analyses were performed using GC/MS in selective ion monitoring mode. Good linearities ($r^2=0.998{\sim}0.999$) in calibration curve and a satisfactory recovery (80.0%~113%) were achieved. Accuracy and precision values within ${\pm}15%$ in the concentration range of 5 to 200 ng/mL were also observed for all compounds. The developed method was applied to pravastatin-treated (70 and 250 mg/kg/day for 7 days, oral) hyperlipidemia rats. Those sterols were significantly lower in drug-treated rats compared to the controls, which justifies the drug efficacy. Therefore, these results indicate that the developed method was successfully applied to examine statin drug efficacy with urine sample.