• Title/Summary/Keyword: HMG-CoA

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Coenzyme Q10: a progress towards the treatment of neurodegenerative disease

  • Kumar, Peeyush;Kumar, Pramod;Ram, Alpana;Kuma, Mithilesh;Kumar, Rajeev
    • Advances in Traditional Medicine
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    • v.10 no.4
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    • pp.239-253
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    • 2010
  • Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

Co-treatment with Fermented Black Raspberry and Red Ginseng Extracts Improves Lipid Metabolism and Obesity in Rats Fed with a High-fat and High-cholesterol Diet (복분자와 홍삼 발효 추출물의 복합투여가 고지방 고콜레스테롤 식이를 섭취한 흰쥐의 지질대사 및 비만에 미치는 영향)

  • Lee, Min Jung;Choi, Hye Ran;Lee, Jung-Hyun;Lee, Su Jung;Kwon, Ji Wung;Choi, Kyung-Min;Cha, Jeong-Dan;Hwang, Seung-Mi;Park, Jong Hyuk;Lee, Sang Cheon;Park, Pill Jae;Lee, Tae-Bum
    • Korean Journal of Food Science and Technology
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    • v.47 no.3
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    • pp.364-372
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    • 2015
  • This study investigated the effects of fermented black raspberry (BR) and red ginseng (RG) extract co-treatment on lipid metabolism and obesity in rats fed with a high fat/high cholesterol diet (HFHCD) for 12 weeks. Compared to the corresponding values in rats fed with a HFHCD, total cholesterol and low-density lipoprotein (LDL)-cholesterol and triglyceride levels decreased whereas high-density lipoprotein (HDL)-cholesterol levels increased in rats treated with fermented BR and RG extracts. These extracts significantly increased the expression of HMG-CoA reductase, LDL receptor, and sterol regulatory-element-binding protein-2 (SREBP-2) mRNA, but decreased the mRNA expression of SREBP-1. Additionally the serum levels of leptin and fatty acid synthase were decreased. Moreover, supplementation with fermented BR and RG effectively increased fecal cholesterol excretion. These results suggest that fermented BR and RG extracts might be effective at preventing hypercholesterolemia and obesity.

Effects of Defatted Soybean Grits on Lipid Metabolism in Rats Fed with High-fat Diet (탈지대두 grits가 고지방식이를 투여한 흰쥐의 지질대사에 미치는 영향)

  • Kim, Hyun-Jeong;Ji, Young-Ju;Lee, Sung-Gyu;Choi, Jun-Hyeok;Lee, Eun-Ju;Jeong, Hyun-Jin;Lee, Sam-Pin;Lee, In-Seon
    • Korean Journal of Food Science and Technology
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    • v.40 no.5
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    • pp.580-585
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    • 2008
  • The principal objective of this study was to determine the effects of defatted soybean grits (DSG) on body lipidmetabolism with 4 weeks of feeding on a high-fat diet. The rats were divided into the following 4 groups: control group (Con), control group treated with 20% DSG (C20D), high-fat group (HF), and high-fat group treated with 20% DSG (HF20D). The plasma total cholesterol and LDL-cholesterol concentrations were significantly lower in the HF20D group than in the HF group. On the other hand, the DSG supplement resulted in a significant increase in plasma HDL-cholesterol levels. The DSG supplement reduced the hepatic total lipid, total cholesterol, and triglyceride contents as compared to what was observed in the HF diet groups. In addition, the fecal total cholesterol and triglyceride contents increased in the DSG treatment groups. The hepatic HMG-CoA reductase activities were demonstrated to be significantly lower in the HF20D group than in the HF group. These results showed that the DSG powder lowered plasma cholesterol levels, tissue lipid contents, and cholesterol accumulation in the rats.

Effects of Medicinal Plants on the Quality and Physiological Functionalities of Traditional Ginseng Wine (각종 약용 식물 첨가가 전통 인삼주의 품질 특성과 생리기능성에 미치는 영향)

  • Lee, Eun-Na;Lee, Dae-Hyoung;Kim, Sin-Bum;Lee, Seung-Whan;Kim, Na-Mi;Lee, Jong-Soo
    • Journal of Ginseng Research
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    • v.31 no.2
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    • pp.102-108
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    • 2007
  • The goal of this study was to develop a highly valuable Korean traditional ginseng wine containing various bioactive compounds with good acceptability. The effect of some medicinal plants on the quality and physiological functionality of Korean traditional ginseng wine were investigated. Advanced traditional ginseng wine (AG wine) prepared by addition of 0.5% each Pleuropterus multflorus and Pueraria lobata into the rice mash containing 1% ginseng, 0.4% Fermivin(commercial alcohol fermentation yeast) and Koji (2:1 mixture of nuruk and amylase containing 36 Saccharogenic power per g) showed the highest acceptability and ethanol content (16.8%). Changes of functionalities of the AG wine during fermentation at $25^{\circ}C$ for 30 days were investigated. The highest antihypertensive angiotensin I-converting enzyme inhibitory activity (78.9%) and total acceptability of the AG wine were shown after fermentation at $25^{\circ}C$ for 20 days. However, antioxidant activity, SOD-like activity and fibrinolytic activity of the AG wines were not detected or very low. HMG-CoA reductase inhibitory activity of the AG wine was also shown to be 8.2% and 9.2% after fermentation for 15 days and 20 days, respectively.

Lovastatin biosynthesis enhanced by thiamine in Aspergillus terreus

  • An, U-Seok;Han, Gyu-Beom
    • 한국생물공학회:학술대회논문집
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    • 2002.04a
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    • pp.184-187
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    • 2002
  • Lovastatin is a cholesterol-lowering agent, which plays a role of an inhibitor of 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMG-CoA). When thiamine was supplemented in 3L batch fermentation, the production of lovastatin was improved. At the same time, the levels of pyruvic acid and NAD(P)H were estimated in the course of the fermentation of A. terreus. For the high level production of lovastatin, semi fed-batch fermentation was performed. And the thiamine level was maintained to a concentration of 20 mg/L and glucose was supplied. The final dry cell weight was lowered by 30 % and final lovastatin concentration was increased by 33 %. Final lovastatin concentration of 3.3 g/L was achieved in 8 days.

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Mevinolin Production by Monascus pilosus IFO 480 in Solid State Fermentation of Soymeal

  • Pyo, Young-Hee;Lee, Young-Chul
    • Food Science and Biotechnology
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    • v.15 no.4
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    • pp.647-649
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    • 2006
  • Mevinolin, a fungal metabolite, is a potent inhibitor of 3-hydroxy-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-controlling enzyme in cholesterol biosynthesis. In this investigation, the optimum factors for mevinolin production by Monascus pilosus IFO 480 in soymeal fermentation were studied. The highest yield of mevinolin, 2.82 mg mevinolin per g dry weight, without citrinin (a toxic fungal secondary metabolite) was obtained after 21 days of fermentation at $30^{\circ}C$ at 65% moisture content, particle size 0.6-0.9 mm, and initial substrate pH of 6.0. Mevinolin was present in the fermentation substrate predominantly in the hydroxycarboxylate form (open lactone, 92.1-97.3%), which is currently being used as a hypocholesterolemic agent.

Molecular Cloning and Analysis of the Gene for P-450 Hydroxylase from Pseudonocardia autotrophica IFO 12743

  • Kim, Jung-Mee;Younmie Jin;Hyun, Chang-Gu;Kim, Jong-Hee;Lee, Hong-Sub;Kang, Dae-Kyung;Kang, Dae-Jung;Kim, Tae-Yong;Suh, Joo-Won
    • Journal of Microbiology
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    • v.40 no.3
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    • pp.211-218
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    • 2002
  • A 4.8-kb DNA fragment encoding the P-450 type hydroxylase and ferredoxin genes was cloned from Pseudonocardia autotrophica IFO 12743 that can convert vitamin D$\_$3/ into its hydroxylated active forms. In order to isolate the P-450 gene cluster in this organism, we designed PCR primers on the basis of the regions of an oxygen binding site and a heme ligand pocket that are general characteristics of the P-450 hydroxylase. Sequencing analysis of the BamHI fragment revealed the presence of four complete and one incomplete ORFs, named PauA, PauB, PauC, and PauD, respectively. As a result of computer-based analyses, PauA and PauB have homology with enoyl-CoA hydratase from several organisms and the positive regulators belonging to the tetR family, respectively. PauC and PauD show similarity with SuaB/C proteins and ferredoxins, respectively, which are composed of P-450 monooxygenase systems for metabolizing two sulfonylurea herbicides in Streptomyces griseolus PauC shows the highest similarity with another CytP-450$\_$Sca2/ protein that is responsible for production of a specific HMG-CoA reductase inhibitor, pravastatin, in S. carbophilus. Cultures of Steptomyces lividans transformant, containing the P-450 gene cluster on the pWHM3 plasmid, was unable to convert vitamin D$\_$3/ to its hydroxylated forms.

Incidence level of abnormality in creatine phosphokinase by statin

  • Kim, Yoo-Ni;Bae, Kyun-Seop;Jung, Sun-Hoi;Lee, Seung-Mi;Yoon, Kyoung-Eun;Kim, Hwa-Young;Chae, Young-Moon;Park, Byung-Joo
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.237-237
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    • 2002
  • Creatine phosphokinase (CPK) was a marker in diagnosis of rhabdomyolysis. The CPK abnormality could be induced by intake of HMG CoA reductase inhibitors (statins). The objective of this study was to estimate the incidence rate of CPK abnormality by each statin. (omitted)

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An Efficient Method for the Large-Scale Synthesis of Atorvastatin Calcium

  • Lee, Hong-Woo;Kim, Young-Min;Yoo, Choong-Leol;Kang, Sung-Kwon;Ahn, Soon-Kil
    • Biomolecules & Therapeutics
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    • v.16 no.1
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    • pp.28-33
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    • 2008
  • Atorvastatin calcium salt (1) was obtained through the preparation of lactone compound (8) from 2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-ethyl)-2-phenyl-1,3,2-dioxaborinan-4-yl)acetic acid tert-butyl ester (9) by hydrolysis in basic condition. Efficient hydrolysis of boronate compound 9 aimed at the viable synthesis for commercial production and purification of Atorvastatin calcium is reported. Detail studies of evaluation procedure are also reported.

The Effect of Bupleuri Radix Herbal-acupuncture at GB34(Yangneungcheon) on Hyperlipidemia in Rats (양릉천 시호 약침이 고지혈증에 미치는 영향)

  • Park, Jae-Young;Song, Choon-Ho
    • Korean Journal of Acupuncture
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    • v.27 no.2
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    • pp.121-140
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    • 2010
  • Objectives & Methods : The purpose of this study is to observe the effects of Bupleuri Radix Herbal-acupuncture at GB34(Yangneungcheon) of hyperlipidemic rats. The author performed several items to analyze body-weight of the rats, weight of its liver, serum as well as urine changes in each group. Results : 1. Bupleuri Radix herbal-acupuncture(BR-HA) infused solution (MCR-HAS) increased both DPPH radical scavenging activity and HMG-CoA reductase inhibition rate in rat liver cells. 2. BR-HA at GB34 significantly decreased the level of serum total cholesterol and atherogenic index(AI), while significantly increased the ratios of high-density lipoprotein (HDL)/total cholesterol and phospholipid/total cholesterol in hyperlipidemic rats. 3. BR-HA at GB34 significantly decreased urine glucose in hyperlipidemic rats. Conclusions : From the results above, it is suggested that Bupleuri Radix herbal -acupuncture at GB34 has a therapeutic effect on hyperlipidemia.