• 제목/요약/키워드: HMG-Co A reductase

검색결과 229건 처리시간 0.021초

Enhancement of artemisinin content by constitutive expression of the HMG-CoA reductase gene in high-yielding strain of Artemisia annua L.

  • Nafis, Tazyeen;Akmal, Mohd.;Ram, Mauji;Alam, Pravej;Ahlawat, Seema;Mohd, Anis;Abdin, Malik Zainul
    • Plant Biotechnology Reports
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    • 제5권1호
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    • pp.53-60
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    • 2011
  • Artemisinin is effective against both chloroquine-resistant and -sensitive strains of Plasmodium species. However, the low yield of artemisinin from cultivated and wild plants is a serious limitation to the commercialization of this drug. Optimization of artemisinin yield either in vivo or in vitro is therefore highly desirable. To this end, we have overexpressed the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) gene (hmgr) from Catharanthus roseus L. in Artemisia annua L. and analyzed its influence on artemisinin content. PCR and Southern blot analyses revealed that the transgenic plants showed stable integration of the foreign hmgr gene. The reverse transcriptase-PCR results suggested that the hmgr was expressed at the transcriptional level in transgenic lines of Artemisia annua L., while the high-performance liquid chromatography analysis showed that artemisinin content was significantly increased in a number of the transgenic lines. Artemisinin content in one of the A. annua transgenic lines was 38.9% higher than that in non-transgenic plants, and HMGR enzyme activity in transgenic A. annua L. was also higher than that in the non-transgenic lines.

An Efficient Approach for Cloning P450 Hydroxylase Genes from Actinomycetes

  • Hyun, Chang-Gu;Kim, Jung-Mee;Hong, Soon-Kwang;Suh, Joo-Won
    • Journal of Microbiology and Biotechnology
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    • 제8권3호
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    • pp.295-299
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    • 1998
  • Oligonucleotide primers were designed and successfully applied to amplify DNA fragments of P450 hydroxylase genes from actinomycetes which produce a large variety of medically important metabolites. Primers were designed based on several regions of strong similarities in amino acid sequence of P450 hydroxylases from a variety of actinomycetes, primarily in the regions of an oxygen binding site and a heme ligand pocket. These primers were used to amplify DNA fragments from seven different actinomycetes species producing a variety of different compounds. The deduced amino acid sequences of the isolated fragments revealed significant similarities to known P450 hydroxylase including the product of the suaC or subC genes from Streptomyces griseolus that is capable of metabolizing a number of sulfonylurea herbicides, and to the product of the $P450_{sca2}$ from S. carbophilus that produces a specific HMG-CoA reductase inhibitor. This method should help researchers in cloning the P450 hydroxylase genes involved in the biosynthesis of useful compounds.

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Increased Hepatic Lipogenesis Elevates Liver Cholesterol Content

  • Berger, Jean-Mathieu;Moon, Young-Ah
    • Molecules and Cells
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    • 제44권2호
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    • pp.116-125
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    • 2021
  • Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

손바닥선인장 복합물이 Streptozotocin으로 유발된 당뇨 쥐의 지질대사에 미치는 효과 (Effects of Opuntia ficus-indica Complex on Lipid Metabolism in Streptozotocin-induced Diabetic Rats)

  • 윤진아
    • 한국식품영양학회지
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    • 제26권3호
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    • pp.526-534
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    • 2013
  • This study was conducted to examine the effects of Opuntia ficus-indica complex (OF) on the lipid metabolism, bile acid in feces, alanine aminotransferase (ALT) activity, aspatate aminotransferase (AST) activity, composition of urine and expression of cholesterol related mRNA in streptozotocin (STZ)-induced diabetic rats. Thirty two male Sprague-Dawley rats were randomly divided into non-diabetic control (NC), diabetic control (DC), diabetic OF of 2% (OF-2) and diabetic OF of 5% (OF-5), then each group was fed for 3 weeks. Plasma total cholesterol, non-esterified fatty acids (NEFA), total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL) were decreased significantly (p<0.05) in OF-5 group compared to DC, but high density lipoprotein (HDL) was not changed. AST and ALT were also reduced and bile acid excretion was improved. Composition of urine in OF-5 was almost same in NC. The expression of cholesterol $7{\alpha}$-hydroxylase (CYP7A1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R), Low density lipoprotein receptor (LDL-R) mRNA indicated that feeding OF have the effects of cholesterol decreation in plasma by synthesis of bile acid from cholesterol. These results provide experimental evidence about improved lipid metabolism of the OF feeding in the STZ-induced diabetic rats.

B16 흑색종세포에서 로바스타틴에 의한 멜라닌 합성 촉진효과에 미치는 산화질소의 역할 (Role of Nitric Oxide in the Lovastatin-Induced Stimulation of Melanin Synthesis in B16 Melanoma Cells)

  • 이용수
    • 약학회지
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    • 제57권6호
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    • pp.388-393
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    • 2013
  • Previously, we have reported that lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, increased melanin synthesis through intracellular $Ca^{2+}$ release in B16 cells. In this study we investigated the possible involvement of nitric oxide (NO) in the mechanism of lovastatin-induced melanogenesis. Lovastatin elevated NO formation in a dose-dependent manner. Treatment with mevalonate, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP), precursors of cholesterol, did not significantly alter the lovastatin-induced NO production, suggesting that inhibition of cholesterol metabolism may not be involved in the mechanism of this action of lovastatin. Both NO formation and melanogenesis induced by lovastatin was significantly suppressed by treatment with $N^G$-nitro-L-arginine methyl ester (L-NAME) and 2-(4-carboxy-2-phenyl)-4,4,5,5-tetramethylinidazoline-1-oxyl-3-oxide (cPTIO), an inhibitor of NO synthase and a NO scavenger, respectively. The lovastatin-induced NO production was significantly affected not by EGTA, an extracellular $Ca^{2+}$ chelator, but by an intracellular $Ca^{2+}$ chelator (BAPTA/AM) and intracellular $Ca^{2+}$ release blockers (dantrolene and TMB-8). Taken together, these results suggest that lovastatin may induce melanogenesis through NO formation mediated by intracellular $Ca^{2+}$ release in B16 cells. These results further suggest that lovastatin may be a good candidate for the therapeutic application of various hypopigmentation disorders.

건조 방법에 따른 산사과 추출물의 항산화 및 생리활성 (Antioxidant abilities and physiological properties of dried Haw extracts prepared using different drying methods)

  • 남산;권유리;정헌식;윤광섭
    • 한국식품저장유통학회지
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    • 제23권2호
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    • pp.246-251
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    • 2016
  • 건조 방법을 달리하여 건조한 산사과 추출물의 항산화활성 및 생리활성의 특성을 비교하였다. 건조 산사과의 추출 수율은 동결건조 추출물이(61.70%) 열풍건조 추추물(53.50%) 보다 높은 값을 나타내었으며, 총 폴리페놀과 플라보노이드 함량에서도 동결건조 산사과 추출물이 열풍건조 추출물에 비하여 높은 값을 보였다. 항산화 활성 또한 동결 건조 산사과 추출물에서 열풍 건조 산사과 추출물보다 높은 활성을 나타내었고, 특히 DPPH 라디칼 소거능에서 동결건조 산사과 추출물이 열풍건조 산사과 추출물 보다 3배 넘는 활성을 나타내었다. ${\alpha}-Glucosidase$ inhibitory ability에서는 동결건조 산사과가 열풍건조 산사과, 양성대조군인 acarbose보다 높은 활성을 나타내었으며, HMG-CoA reductase 저해활성에서는 동결, 열풍 산사과 추출물이 전체적으로 높은 저해 활성을 나타내어 콜레스테롤 개선효과에 대한 가능성을 나타내었다. 이러한 결과를 종합해 볼 때 동결건조 방법을 이용하는 것이 산사과의 건조효율 증대와 품질손상을 억제 할 수 있는 건조 방법으로 판단된다.

양릉천 갈근 약침이 흰쥐의 고지혈증에 미치는 영향 (The Effect of Puerariae Radix Herbal-acupuncture at $GB_{34}$(Yangleungcheon) on Hyperlipidemia in Rats)

  • 송왕기;강재희;이현
    • Journal of Acupuncture Research
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    • 제26권4호
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    • pp.79-90
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    • 2009
  • Objectives & Methods : The purpose of this study is to observe the effects of Puerariae Radix Herbal-acupuncture at $GB_{34}$(Yangleungcheon) on hyperlipidemia in rats. The author made several items to compare body-weight of the rats, weight of its liver, serum, enzymes in liver as well as the histological changes in each group. Results : 1. In the Puerariae Radix herbal-acupuncture group, there was a significant improvement of the levels of total cholesterol, HDL-cholesterol, atherosclerosis index and phospholipid in serum as compared with the control group but there was no significant difference as compared with the NP or saline group. 2. There was a significant improvement of HMG-CoA reductase activity and catalase level in Puerariae Radix herbal-acupuncture group as compare with the control group, the NP group and the saline group. 3. The pathohistological changes of liver and aorta was suppressed in the Puerariae Radix herbalacupuncture group than the control group. Conclusions : From the above results, it is suggested that Puerariae Radix herbal-acupuncture at GB34 has a therapeutic effect on hyperlipidemia.

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Lipid-lowering and Antioxidant Effects of Curcuma Radix in Poloxamer 407-induced Hyperlipidemia Model Rat Models

  • Park, So-Ae;Jo, Hyun-Kyung;Yoo, Ho-Ryong;Kim, Yoon-Sik;Seol, In-Chon;An, Joung-Jo
    • 대한한방내과학회지
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    • 제32권2호
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    • pp.243-258
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    • 2011
  • Objectives : This study investigated the hypolipidemic and antioxidant effects of Curcuma radix using a rat model induced by poloxamer 407 injection. Methods : Serum lipid parameters and oxidative stress-associated biomarkers were determined. Additionally, hepatic cholesterol and triglyceride as well as lipid metabolism-associated gene expressions were observed in hepatic tissue. Results : 1. Curcuma radix ameliorated elevation of serum cholesterol, triglyceride, LDL-cholesterol, MDA, hepatic cholesterol level, and reduction of serum TAC, SOD, GSH, GSH-reductase level. 2. Curcuma radix augmented up-regulated ACAT gene expression. 3. Curcuma radix almost completely ameliorated down-regulated CYP-7A1 but up-regulated HMG-CoA gene expression. Conclusions : The hypolipidemic and antioxidant properties of Curcuma radix were evidenced. This study provides a scientific basis for the clinical application of Curcuma radix and development of hypolipidemics using this herb in the future.

Quality Characteristics and Cardiovascular Activities of Korean Traditional Wines and Liquors

  • Yu, Hyung-Eun;Lee, Dae-Hyoung;Lee, Ju-Hyun;Choi, Sin-Yang;Lee, Jong-Soo
    • Food Science and Biotechnology
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    • 제14권6호
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    • pp.772-777
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    • 2005
  • The goal of this study was to screen and characterize the physiological functions of Korean traditional wines (TW) and liquors (TL). Forty-two TW and TL were collected and evaluated for quality and cardiovascular activities. Ethanol content ranged from $9.0%{\sim}41%$, and pH ranged from $3.0{\sim}7.8$, and they also contained 0.01% to 0.67% of total acid. Samples contained a maximum of 2.0% of crude protein and $0.1%{\sim}14.0%$ of reducing sugar. Commercial CM-wine showed the highest antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity, 85.9%. The greatest fibrinolytic activity and platelet aggregation inhibitory activity were also found in commercial CM-wine (31.8U) and commercial SS2-wine (38.6 %), respectively. Commercial SHBI-liquor showed the highest HMG-CoA reductase inhibitory activity, 78%. The ACE inhibitor from commercial CM-wine was a peptide compound and also showed an antihypertensive effect in spontaneous hypertensive rats at a dosage of 1.5 mg/kg.

HK-1000 약침이 흰쥐의 고지혈증 및 동맥경화증에 미치는 영향 (A Study on the Effect of Herbal-acupuncture with HK-1000 Solution on Hyperlipidemia and Arteriosclerosis Induced Rats)

  • 박치영;홍권의
    • 대한약침학회지
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    • 제11권3호
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    • pp.55-66
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    • 2008
  • Objective&Methods: The purpose of this study is to observe the effects of HK-1000 Herbal-acupuncture solution at GB34(Yangleungchean) on hyperlipidemia and arteriosclerosis in rats. The author performed several experimental items to analyze the levels of various components and enzymes in serum, urine and liver, as well as the histological change of liver and aorta. Results: 1. HK-1000 herbal-acupuncture infusion increased the cell viability rate, DPPH radical scavenging activity and HMG-CoA reductase inhibition rate in rat liver cells. 2. The levels of total cholesterol, free cholesterol, LDL-cholesterol, phospholipid in serum and AI(atherogenic index) were decreased, and the ratio of HDL to TCL(HDL/TCL) and the level of TG in serum were increased as compared with those of the control group. 3. In the HK-1000 group, serum AST and ALT were significantly lower than those of the HG group and saline group. 4. Hepatic GSH and catalase activities were significantly increased as compared with those of the saline group. Conclusions: From the above results, it is suggested that HK-1000 herbal-acupuncture at GB34 has a therapeutic effect on hyperlipidemia and arteriosclerosis.