• Title/Summary/Keyword: 3-hydroxy-3-methylglutaryl-CoA reductase

Search Result 81, Processing Time 0.031 seconds

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
    • /
    • v.16 no.1
    • /
    • pp.28-33
    • /
    • 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.

Effects of Dietary Garlic Powder on Growth Performance and mRNA Expression of Hepatic HMG-CoA Reductase in Broiler Chickens (육계 사료 내 마늘분말의 첨가급여가 육계 성장과 HMG-CoA Reductase의 mRNA 발현에 미치는 영향)

  • You, Sun-Jong;Ahn, Byoung-Ki;Kang, Chang-Won
    • Journal of Animal Science and Technology
    • /
    • v.51 no.4
    • /
    • pp.307-314
    • /
    • 2009
  • This experiment was conducted to investigate the effects of dietary garlic powder (GP) on growth performance and mRNA expression of hepatic 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) in broiler chickens. Day-old male chicks (Ross, n=270) were fed diets containing 0% [positive control (PC) with antibiotics or negative control (NC) without antibiotics], 1%, 3% and 5% GP for 6 wks. There were no significant differences in feed intake among the treatments throughout the experimental period. Body weight gains in groups fed dietary GP at 3% and 5% were significantly higher than that of NC group (P<0.05). Feeding GP up to 5% did not exert any adverse effect on weight gain and feed intake. There were no significant differences in the relative weights of liver, spleen, cecum and breast muscle. The content of meat cholesterol in GP containing dietary groups tended to be reduced as compared to NC group. Average infectious bronchitis antibody titers in chicks fed GP containing diets were significantly higher than that of NC group (P<0.05). The mRNA expression of hepatic HMG-CoA reductase was reduced by dietary GP. These results indicate that dietary GP has growth promoting effects and tended to alter cholesterol metabolism in broiler chickens.

Phenylpropanoids from Myristica fragrans Houtt (육두구(Myristica fragrans Houtt)로부터 Phenylpropanoid의 분리)

  • Song, Myoung-Chong;Ahn, Eun-Mi;Bang, Myun-Ho;Kim, Se-Young;Rho, Yeong-Deok;Kwon, Byuong-Mog;Lee, Hyun-Sun;Baek, Nam-In
    • Applied Biological Chemistry
    • /
    • v.47 no.3
    • /
    • pp.366-369
    • /
    • 2004
  • Myristica fragrans Houtt were extracted in 80% aq. MeOH and solvent fractionated sing $CHCl_3$, EtOAc, n-BuOH and water, successively. The n-BuOH fraction gave three phenylpropanoids through application of silica gel column chromatographies. The chemical structures of the phenylpropanoids were determined by the interpretation of several spectral data, including NMR and MS as meso-dihydroguaiaretic acid (1), nectandrin B (2) and syringin methyl ether (3). Compound 1, which was first isolated from this plant by authors, showed inhibitory activities with $60.0{\pm}2.1%\;(100\;{\mu}g/ml),\;42.6{\pm}0.9%\;(140\;{\mu}g/ml)\;and\;12.2{\pm}0.2%\;(200\;{\mu}g/ml)$ on ACAT(acyl-CoA:Cholesterol Acyltransferase), chitin synthase III and HMG-CoA reductase (3-hydroxy-3-methylglutaryl coenzyme A reductase), respectively. Compound 3 showed inhibitory activities with $27.2{\pm}0.9%\;(100\;{\mu}g/ml),\;45.5{\pm}0.8%\;(200\;{\mu}g/ml)$ on ACAT and chitin synthase III.

Effect of Probiotics-Fermented Samjunghwan on Differentiation in 3T3-L1 Preadipocytes (3T3-L1 전지방세포에서 발효 삼정환의 지방 분화 억제 효과)

  • Song, Mi-Young;Bose, Shambhunath;Kim, Ho-Jun
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.42 no.1
    • /
    • pp.1-7
    • /
    • 2013
  • Samjunghwan (SJH) was fermented using five different probiotic bacterial strains (Lactobacillus plantarum, Enterococcus faecium, Pediococcus pentosaceus, Lactobacillus acidophilus or Bifidobacterium longum) separately. We examined the inhibition of preadipocyte differentiation through Oil Red O staining and analyzed the expression of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EPB{\alpha}$), peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), uncoupling protein (UCP)-2, and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which are adipogenic transcription factors. Both Lactobacillus plantarum and Enterococcus faecium-fermented SJH reduced Oil Red O dye staining compared with the same dose of non-fermented SJH. Only Lactobacillus plantarum-fermented SJH inhibited all adipogenic transcription factors and showed the best down-regulation of $PPAR{\gamma}$, UCP-2, and HMG-CoA reductase compared with the same dose of non-fermented SJH. The effect of SJH on the inhibition of preadipocyte differentiation was more prominent from the fermented SJH. Lactobacillus plantarum-fermented SJH, in particular, blocks the expression of $PPAR{\gamma}$, UCP-2, HMG-CoA reductase.

Expression Patterns of Genes Involved in Carotenoid Biosynthesis in Pepper

  • Ha, Sun-Hwa;Lee, Shin-Woo;Kim, Jong-Guk;Hwang, Young-Soo
    • Journal of Applied Biological Chemistry
    • /
    • v.42 no.2
    • /
    • pp.92-96
    • /
    • 1999
  • To study the regulatory mechanism of isoprenoid (carotenoid) biosynthesis, we have compared the expression patterns of nine isoprenoid biosynthetic genes in Korean red pepper (Capsicum. annuum cv. NocKaung). The expression of geranylgeranyl pyrophosphate synthase gene was initially induced at early ripening stage (I1) and was rather slightly decreased during pepper fruit ripening. The ex-pression of phytoene synthase gene was strongly induced at semi-ripening stage (I2) and the phytoene desaturase transcript was maximally induced at the fully ripened stage (R). Our results suggest that genes encoding two 3-hydroxy-3-methylglutaryl-CoA reductase isozymes (HMGR1 and HMGR2) and farnesyl pyrophosphate synthase might be not so critical in pepper carotenoid biosynthesis but three genes encoding geranylgeranyl pyrophosphate synthase, phytoene synthase and phytoene desaturase were induced in a sequential manner and coordinately regulated during the ripening of pepper fruit.

  • PDF

Screening and Characterization of Anticholesterogenic Substances from Edible Plant Extracts (식용식물 추출물로부터 콜레스테롤 합성 저해제의 검색 및 분리)

  • Park, Jeong-Ro;Park, Jong-Cheol;Choi, Seong-Hee
    • Journal of the Korean Society of Food Science and Nutrition
    • /
    • v.26 no.2
    • /
    • pp.236-241
    • /
    • 1997
  • Inhibitory effects of several edible plant extracts against 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase, a rate-limiting enzyme in the biosynthesis of cholesterol, were screened. Inhibition rates of $10{\sim}15%$ were observed with hot water extracts of Allium fistulosum, Allium sativum and Cucurbita maxima. Methanol extracts of Aster scaber, Allium sativum, Zingiber officinale, Oenanthe javanica and Angelica keiskei effectively reduced the enzyme activity with inhibition rates of $29{\sim}51%$. The methanol extract of Angelica keiskei was fractionated sequentially with chloroform, ethyl acetate and n-butanol. Of the fractions ethyl acetate fraction showed the highest inhibition against the enzyme. $Luteolin-7-O-{\beta}-D-glucoside$ and hyperoside isolated from the ethyl acetate fraction of Angelica keiskei inhibited the enzyme activity by 65.5% and 14.8%, respectively, at the concentration of $30{\mu}M$.

  • PDF

Studies on the Development of Antihyperlipidemic Drugs from Oriental Herbal Medicines(I) -Antihyperlipidemic Activities of Oriental Herbal Medicines- (한방약물로부터 항고지혈증 치료약물개발(I) -수종 한약재의 항고지혈증 활성검색-)

  • Jung, Eun-Ah;Kim, Dong-Hyun;Lee, Sang-In;Kim, Nam-Jae
    • Korean Journal of Pharmacognosy
    • /
    • v.30 no.4
    • /
    • pp.368-376
    • /
    • 1999
  • Twenty-four Oriental herbal medicines including Platycodi Radix and Scutellariae Radix, etc., which have been used for the cure of hyperlipidemia, coronary heart, disease were evaluated for the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA) reductase inhibition and antioxidant effect on a free radical, 1,1-diphenyl-2-picrylhydrazyl(DPPH) in vitro, and antihyperlipidemic effect on hyperlipidemic rats induced by Triton WR-1339 in vivo. 80% MeOH extract of eight herbs including Scutellariae Radix, Coptidis Rhizoma, Paeoniae Radix Rubra, Moutan Cortex Radicis, Angelicae Gigantis Radix, Bambusae Caulis in Taeniam, Cinnamomi Ramulus and Crataegi Fructus inhibited the HMG-CoA reductase activities and exhibited a radical-trapping action on a stable free radical, DPPH. On Triton WR-1339-induced hyperlipidemic rats, four herbs including Scutellariae Radix, Angelicae Gigantis Radix, Bambusae Caulis in Taeniam and Cinnamomi Ramulus showed respectively the significant suppression of serum total cholesterol, triglyceride, phospholipid and LDL-cholesterol levels and serum transaminase(ALT and AST) activities. From these results, it is suggested that each 80% MeOH extract of Scutellariae Radix, Angelicae Gigantis Radix, Bambusae Caulis in Taeniam and Cinnamomi Ramulus have effective antihyperlipidemic action against hyperlipidemia.

  • PDF

Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase

  • Lew, Lee-Ching;Choi, Sy-Bing;Khoo, Boon-Yin;Sreenivasan, Sasidharan;Ong, Kee-Leong;Liong, Min-Tze
    • Food Science of Animal Resources
    • /
    • v.38 no.2
    • /
    • pp.350-361
    • /
    • 2018
  • Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.

Effects of Methanol Extract of Prosomillet on Cholesterol and Fatty Acid Metabolism in Rat

  • Cho, Sung-Hee;Jung, Seung -Eun;Lee, Hye-Kyung;Ha, Tae-Youl
    • Preventive Nutrition and Food Science
    • /
    • v.4 no.3
    • /
    • pp.188-192
    • /
    • 1999
  • To study effects of methanol extract of prosomillet on lopid metabolism , five groups of male Sprang-Dawley rats weighing 116$\pm$9 g were fed test diets for four weeks. The five diets consisted of one low fat(5% w/w) diet containing starch as carbohydrate source(normal) and four high fat diets(15% w/w) containing 40.5%(w/w)sucrose(control) and additional 80% nethanol extractof prosomillet at the levels of 0.3% and 1%(w/w) or prosomillet powder at the level of 20%(w/w). Serum level of total cholesterol was a little higher but that of triglyceride was 41% lower in 20% (w/w) prosomillet powder group than in the control group. The cholesterol levels of two Liver cholesterol levels were lower and phospolipid levels higher in all three prosomillet powder group . Fecal excretionof bile acid was most increased in the prosomillet powder group among all five test groups. Acitivity of liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase was significantly lower in 0.3% methanol extract fed group than the control and also appeared to be reduced in 1% extract fed one, wherease those of 20 cholesterol 7$\alpha$-hydroxylase were not different among the five groups. Activities of liver cytosilic glucose-6-phosphate dehydrogenase(G6PDH) and malic enzyme were decreased in 0.3% prosomillet methanol extract and 20% powder groups. The results indicate that in addition to fiber, certain active components in prosomillet have potential to exert hypolipidemic effects via regulating hepatic cholesterogenesis and lipogenesis.

  • PDF

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

  • Yoon, Jin A
    • The Korean Journal of Food And Nutrition
    • /
    • v.26 no.3
    • /
    • pp.526-534
    • /
    • 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.