• 보건행정학회지
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• 제9권3호
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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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• 제14권6호
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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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• 한국생물공학회 2003년도 생물공학의 동향(XII)
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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.

• 한국미생물·생명공학회지
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• 제39권3호
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• pp.281-286
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• 2011

발효새우젓의 에탄올 추출물이 지질대사 개선 효능을 알아보기 위하여 흰쥐에 고지방사료를 식이 시키고 추출물의 경구투여 시킨 후, 혈중 지질 관련 물질의 변화를 측정하였다. 혈청 총 콜레스테롤 함량은 고지방 식이를 급여한 HC, HC-SFSL, HC-SFSH, HC-Lov군 모두 7일차, 14일차에 대조군(NC) 보다 유의하게 증가하였다. HC-SFSH군은 7일차에 330 mg/dl, 14일차에는 277 mg/dl로 HC군에 비하여 31.5%, 40.4%의 유의한 저하효과가 관찰되었으며 양성 대조군인 lovastatin보다 감소율 대비 12.6배 높은 혈중 총 콜레스테롤 저하 효과를 나타내었다. 혈중 TG 함량은 7일차에 HC-SFSL군, HC-SFSH군 그리고 HC-Lov군에서 62 mg/dl, 30 mg/dl, 55 mg/dl로 HC군 85 mg/dl에 비해 각각 27%, 64.7%, 35.2%의 유의성 있게 감소하였다. 혈중 LDL-콜레스테롤 함량은 HC-SFSH군에서 고지방만 급여한 HC군 보다 7일차에 22.4%, 14일차에 36.3% 감소 하였으며 양성 대조군인 lovastatin 투여군 보다 혈중 LDL-콜레스테롤 수치를 2.4~3.2배 감소시키는 것으로 나타났다. 고지방 및 새우젓 에탄올 추출물을 14일간 투여 후 간의 조직학적 관찰을 한 결과, 일반식이를 급여한 NC군의 간조직 세포는 간정맥을 중심을 향하여 규칙적 배열을 이루고 있었으며, 간세포의 핵은 중심에 위치하고 세포질은 균질된 구조였다. 반면 고지방 식이만 급여한 HC군의 간 조직은 간조직의 지방입자가 전체적으로 지방구를 형성하며 세포핵이 한쪽으로 치우쳐져 있으며 세포질도 많이 파열되어 전형적인 지방간 형태를 나타내었다. 특히 HC-SFSH군의 간조직은 HC군에 비하여 지방구의 숫자와 세포질의 파열정도가 뚜렷하게 감소된 것이 관찰되었다.

• 한국식품과학회지
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• 제47권5호
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• pp.658-666
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• 2015

본 연구에서는 Asp. terreus를 접종하여 제조한 황국곡자를 이용하여 지질대사와 관련 조절유전자 및 심혈관질환에 미치는 효능을 확인하고, 고지혈증 개선에 미치는 황국곡자의 효능을 검증하고자 하였다. SD rat을 사용하여 8주 동안 고콜레스테롤 식이와 황국곡자 0.5, 2 g을 경구투여 하였다. 그 결과 간조직에서 황국곡자 투여군은 총 지질의 함량이 감소하였으나 황국곡자가 콜레스테롤 배출에는 크게 영향을 주지 않음을 확인하였다. 간조직 내 LDL 및 HDL 관련 유전자 발현 확인 결과, 콜레스테롤 합성의 가장 중요한 기작인 HMG-CoA reductase, LDL receptor와 SREBP2 발현에서는 고콜레스테롤군보다 유의적으로 모두 증가하여 체내의 콜레스테롤을 낮추는 것으로 판단된다. 또한 간조직의 형태학적 특징을 관찰해본 결과 황국곡자 투여군이 고콜레스테롤군에 비해 간 손상의 정도가 현저히 감소되어 있으며 간세포 내 작은 공포 모양의 지방구가 현저히 줄어들어 있는 것을 확인하였으며 황국곡자를 투여한 군 모두 지방세포 침윤과 같은 지방간 병변의 치료효과를 확인하였다. 결과적으로 황국곡자는 체내의 지질대사에 영향을 끼침에 따라 고지혈증의 개선을 위한 소재로 이용될 수 있을 것으로 판단된다.

• 대한예방한의학회지
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• 제13권1호
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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.

• 대한한의학회지
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• 제30권3호
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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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• 제12권2호
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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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• 제30권4호
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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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• 제42권4호
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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.