• Health Policy and Management
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• v.9 no.3
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• pp.70-94
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• 1999

This paper was performed for a cost-effectiveness analysis of pharmacologic treatment of hypercholesterolemia. Agents modeled were cholestyramine, gemfibrozil. bezafibrate, lovastatin, pravastatin, simvastatin. Pharmacologic effectiveness was estimated by regression from reported clinical trials. Pharmacologic effects were expressed as the percent change of blood cholesterol level. Cost estimates included patients' travel expenses and time loss as well as resource consumption in the health care sector. Bezafibrate was the most efficient agent for reducing total cholesterol levels, having an cost over 1 year of ￦31.400 per percent reduction in total cholesterol. Simvastatin (10mg/d) was also efficient(￦33,100 per percent reduction). Chole styramine(8g/d) was least efficient at ￦90,200. For low-density lipoprotein cholesterol. simvastatin(10mg/d) was most efficient, at ￦23,200 per percent reduction, followed by lovastatin(20mg/d) at ￦28,000. Gemfibrozil was least efficient at ￦77,800 per percent reduction. For high-density lipoprotein cholesterol. bezafibrate(400mg/d) was most efficient at ￦39,300 per percent increase of high-density lipoprotein cholesterol. Cholestyramine was least efficient at ￦514,700. Analyses combining low-density lipoprotein cholesterol and high-density cholesterol effects suggest that bezafibrate(600mg/d) and simvastatin (10mg/d) were most efficient for reducing cardiovascular risk. The cost-effectiveness analysis results show that both simvastatin and bezafibrate could be efficient treatment. Simvastatin provide more effective treatment at higher cost, whereas bezafibrate is more cost-effective, as it may be less effective, at lower cost. Therefore, clinicians should choose reasonable treatment according to the patient's needs This pharmacoeconimc analysis will provide a guideline for efficient pharmacologic treatment and also be reference data for pricing new drugs.

• Food Science and Biotechnology
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• v.14 no.6
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• pp.727-731
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• 2005

Synthesized Ile-Ala-Val-Pro (IAVP) peptide, which has the highest hypocholesterolemic effect among a number of synthesized derivatives of Ile-Ala-Val-Pro-Gly-Glu-Val-Ala (IAVPGEVA) isolated from 11S globulin of soy protein by pepsin digestion, was selected for investigation in the present study. Using a recombinant Syrian hamster 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), we studied in detail the inhibition of this enzyme by IAVP and compared the action of this peptide to that of lovastatin, a known competitive inhibitor of this enzyme. The concentration of IAVP required for 50% inhibition ($IC_{50}$) of HMGR activity in given experimental conditions was $340\;{\mu}M$. Kinetic analysis revealed that the studied peptide is a competitive inhibitor of HMGR with respect to both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and nicotinamide adenine dinucleotide phosphate (NADPH), with an equilibrium constant of inhibitor binding ($K_i\;=\;[E][I]/[EI]$) of $61{\pm}1.2\;{\mu}M$ and $157{\pm}4.4\;{\mu}M$, respectively. At the same conditions, $K_i$ and $IC_{50}$ for lovastatin were $2.2{\pm}0.1\;nM$ and 12.5 nM, respectively. Thus, the given peptide interacts with HMGR as a bisubstrate, consequently blocking access of both substrates to the active sites. The achieved results suggest the design of new peptide sequences having a higher relative affinity to binding sites of this enzyme and an enhancement of their hypocholesterolemic properties.

• 한국생물공학회:학술대회논문집
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• 2003.04a
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• pp.223-227
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• 2003

Mevinolic acid (MA), a secondary metabolite produced by a filamentous fungus Aspergillus terreus, is acidic form of lovastatin which has been identified as a powerful cholesterol-lowering agent in humans. When immobilized cell culture was performed, MA production was about 5.3-fold higher than the parallel suspended cell culture. Although the immobilized cells proliferated slowly during exponential in comparison with the suspended cells, oxygen uptake rate and oxygen mass transfer coefficient of the immobilized cell culture were about 1.3- and 2.5- fold higher respectively than those of the parallel suspended cell culture. From these results, it was concluded that MA biosynthesis was closely dependent on the cell growth rate, morphology and oxygen availability.

• Microbiology and Biotechnology Letters
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• v.39 no.3
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• pp.281-286
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• 2011

This study was performed to investigate the effects of salted and fermented shrimp ethanol extract (SFS) on serum lipid metabolism and hepatocytes in rats. Male Sprague-Dawley rats were administered 60% fat feed to induce hypercholesterolemia and were divided into five groups. Experimental groups were classified according to administered diet: normal diet group (NC), high cholesterol diet group (HC), high cholesterol and low dose shrimp extract (20 mg/kg) group (HC-SFSL), high cholesterol and high dose shrimp extract (200 mg/kg) group (HC-SFSH), and high cholesterol and lovastatin (20 mg/kg) group (HC-Lov). The experimental diets were fed ad libitum for 14 days. Compared with the control group, the serum cholesterol and triglycerides were 40.4 and 64.7% lower in the group fed HC-SFSH respectively. Low density lipoprotein (LDL)-cholesterol concentration in serum decreased in the HC-SFSH group compared with the HC group. In a histological assay, hepatocytes in the HC group showed that the vacuolated cells by fat appear clear due to the large amount of intracytoplasmic fat, whereas the liver hepatocytes in the group fed SFS effectively decreased fatty liver and intracytoplasmic fats. These results suggest that the extract of salted and fermented shrimp has an antiatherosclerotic effect and may lessen the effects of cardiovascular disease by reducing the cholesterol level in serum.

• Korean Journal of Food Science and Technology
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• v.47 no.5
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• pp.658-666
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• 2015

The aim of this study was to investigate the effects of rice contatining Aspergillus terreus (Hwangkuk, HK) on lipid metabolism in male Sprague-Dawley (SD) rats fed a high-cholesterol diet (HCD) for 8 weeks. SD rats were divided into five groups: Normal, [Negative Control (HCD), Positive Control (lovastatin)], [HK 0.5 g/kg and HK 2 g/kg]. Hepatic total lipids significantly decreased following treatment with rice contatining Asp. terreus. Furthermore, this treatment led to higher expression levels of HMG-CoA reductase, LDL receptor and SREBP2 mRNA in the liver compared with the HCD group. In addition, histopathologic evaluation showed that feeding rats with rice containing Asp. terreus suppressed hepatic steatosis. These results suggest that rice containing Asp. terreus may be able to regulate of cholesterol synthesis and prevent hyperlipidemia.

• Journal of Society of Preventive Korean Medicine
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• v.13 no.1
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• pp.41-58
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• 2009

Objectives: The purpose of this study was to investigate the effects of Hyolbuchukeo-tang extracts on the hyperlipidemia rats induced by high fat diet. Methods and Materials: In vitro; The extracts prepared for Hyolbuchukeo-tang by hot water extraction (HH), fermentation(HF) and UMPM extraction(HU) method. The extracts were examined for levels of polyphenol compounds, antioxidant activities, and inhibitory potencies for HMG-CoA reductase. In vivo; Sprague-Dawley male rats of weighing $150{\pm}5g$ were randomly divided into six groups ; normal control diet(NC), and high fat diet(HC), high fat diet with treated lovastatin of 10mg/kg(PC), high fat diet with Hyolbuchukeo-tang extracts; HH, HF and HU treated extracts of 300mg/kg, respectively. Also, we compared the effects of the extracts of HH, HF and HU on rats fed high fat diet for four weeks. Results: 1. The content of polyphenol compounds and electron donating abilities(EDAs) was the HF higher than HH and HU. The superoxide dismutase(SOD)-like activities were proportionate in consistency and they appeared highly from all extracts. The HMG-CoA reductase inhibition activities was highest activities in the HU. 2. The activities of serum GOT and GPT were significantly lower in the HH and HF groups. The level of serum triglyceride was significantly decreased in the HF group. HH and HU groups were significantly decreased in the atherogenic index(AI). The total cholesterol concentration in liver was significantly decreased in the HF group, and HU showed more significantly decreased in the triglyceride than of the lovastatin. Also, photomicrographs of liver tissue showed higher fat accumulation in the HC group than in the HH, HF and HU groups. Conclusions: These result suggest that the hyper-lipidemia caused by a high fat diet was effectively inhibited the administration of HF and HU.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.86-97
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• 2009

Objectives : This study was aimed to investigate the effects of GamiSamgieum (SGMX) on hyperlipidemia using an animal model. Additionally, the underlying mechanisms were investigated by determination of gene expressions related with lipid metabolism. Methods : Forty mice were selected for use in this experiment, and then divided into five groups; Naive, Induced, SGMX 100, SGMX 200, and Lovastatin group as positive control with 8 mice each, and their blood was collected for analysis of blood and serum parameters. Results : Administration of SGMX significantly inhibited the increase of liver weight and the macrovacuolar cytoplasmic alterations in histopathologic finding. SGMX administration significantly protected the liver from pathologic elevation of AST and ALT and from lipid peroxidation. SGMX administration significantly lowered total cholesterol levels and TG, and partially upregulated the gene expression of LCAT, CYP7A1 and LDL-R receptor. Conclusion : SGMX is suggested to possess hypolipidemic effect, and thus could be a potential candidate for herbal hypolipidemic via further studies.

• Journal of Microbiology and Biotechnology
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• v.12 no.2
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• pp.222-227
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• 2002

Squalene synthase catalyzes the reductive dimerization of two molecules of farnesyl diphosphate to form squalene at the final branch point of the cholesterol biosynthetic pathway. Due to the unique position of this enzyme in the pathway, its inhibitors may have advantages as antihypercholesterolemic agents. Therefore, selective inhibitors of squalene synthase do not prevent the formation of the essential branch products of the isoprene pathway, such as dolichol, coenzyme-Q, and prenylated proteins, as might be expected for inhibitors of enzymes earlier in the pathway; for example, lovastatin and mevalotin. The current study reports that CJ90002, a pentagalloylglucose isolated from Paeonia moutan SIM (Paeoniaceae), which is an important Chinese crude drug used in many traditional prescriptions, was a potent inhibitor of rat microsomal squalene synthase, and also a potent inhibitor of cholesterol biosynthesis in vitro. In addition, the intraperitoneal and oral administration of CJ90002 had a significant lowering effect on plasma cholesterol levels in hamsters.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.279-282
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• 2000

Simple and precise high-performance liquid chromatographic (HPLC) assay was developed and validated for the determination of a HMG-CoA reductase inhibitor, $lovastatin^{TM}$ and its active metabolite (mevinolinic acid) in human plasma. The method involved solid phase extraction of mevinolinic acid and internal standard using Sep-Pak Cartridge. Samples were analyzed by reversed-phase HPLC using $Capcell-Pak\;C_{18}$ column with ultraviolet detection at 238 nm. The quantitation limit of mevinolinic acid was 2 ng/ml and the calibration curve was linear over the range of 2-50 ng/ml $(r^2>0.999)$ with human plasma. The analyses of quality control samples indicated that the normal values could be predicted with an accuracy >97%. The intra- and inter-day coefficients of variation for the analyses were <10%. The average recoveries were similar (79%) for mevinolinic acid and methylmevinolinic acid. The method described has been successfully applied to the quantification of mevinolinic acid in about 1,000 human plasma samples over six-month period.

• BMB Reports
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• v.42 no.4
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• pp.194-199
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• 2009

The effects of the ginsenoside Rb2 (Rb2) on lipid metabolism were characterized in 3T3-L1 adipocytes to evaluate their utility for treating obesity. While the amounts of total cholesterol and triacylglycerol (TAG) were markedly increased in the adipocytes treated with high amounts of cholesterol and fetal bovine serum (FBS), the test groups treated with Rb2 showed levels that were close to normal. The effect of Rb2 on these cells was comparable to that of lovastatin. Rb2 enhanced the expression of the sterol regulated element binding protein (SREBP) mRNA whereas treatment with cholesterol and FBS led to a reduction in the abundance of this transcript. The activity of fatty acid synthetase (FAS) was lower in the cholesterol group compared to the Rb2 treatment group suggesting that the observed decrease in cholesterol levels and activated SREBP was mediated by Rb2. Treatment with Rb2 also resulted in a decrease in TAG levels in adipocytes cultured under high fatty acid conditions. This effect was mediated by stimulating the expression of SREBP and Leptin mRNA, suggesting that Rb2 might be a valuable component capable of lowering the levels of lipids.