• Title/Summary/Keyword: cholesterol biosynthesis

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Compatibility Study of Excipients for Pravastatin Tablet (Pravastatin 정제 연구를 위한 첨가제와의 적합성 연구)

  • Kim, Kang Min
    • Journal of Life Science
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    • v.28 no.4
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    • pp.472-477
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    • 2018
  • Pravastatin sodium is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor used in the treatment of hypercholesterolemia by reducing cholesterol biosynthesis. Pharmaceutical excipients of commonly used including water, diluents, stabilizers, disintegrants, lubricants and colorants, and were identified for compatibility. All tests were performed by means of physical mixture of pravastatin and the excipients, which were placed in a press-through-pack (PTP) and incubated under accelerated conditions ($40^{\circ}C$ and 75% relative humidity) for 3 months. The blends of pravastatin with all excipients developed white, off white, and light brown powders, which showed no changes upon visual analysis. Accelerated conditions changed the degradation profile of pravastatin calcium in the HPLC system when mixed with different excipients. Although most excipients can have minor effects on pravastatin stability, the major degradation product from pravastatin was lactone. Low-level interaction (assay and impurity) was induced by all excipients except for microcrystalline cellulose and croscarmellose sodium. These excipients increased lactone impurity in 3 months by as much as 0.22% and 0.18% respectively. The total mixture slightly increased the lactone impurity (by 0.43% in 3 months) of pravastatin. There was no change in the assays of all excipients. These results will be helpful in studying tablet size reductions for convenience of use.

Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review

  • Castro, Fernanda Cavallari de;Cruz, Maria Helena Coelho;Leal, Claudia Lima Verde
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.8
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    • pp.1065-1074
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    • 2016
  • Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-${\beta}$) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review.

Reduction of Body Weight by Capsaicin is Associated with Inhibition of Glycerol-3-Phosphate Dehydrogenase Activity and Stimulation of Uncoupling Protein 2 mRNA Expression in Diet-induced Obese Rats

  • Ann, Ji-Young;Lee, Mak-Soon;Joo, Hyun-Jin;Kim, Chong-Tai;Kim, Yang-Ha
    • Preventive Nutrition and Food Science
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    • v.16 no.3
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    • pp.210-216
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    • 2011
  • Capsaicin is a pungent component of red pepper, which is widely consumed as food adjuncts. The present study was performed to investigate anti-obesity effects of capsaicin in diet-induced obese rats. Male Sprague-Dawley rats (n=14) were fed with a high-fat diet (Control) or high-fat diet containing 0.016% capsaicin (w/w) (Capsaicin) for 8 weeks. The final body weight and the mass of white adipose tissue were significantly lower in capsaicin supplemented group compared to control. Dietary capsaicin ameliorated lipid profiles with decrease in the plasma concentrations of triglycerides and total cholesterol, and decrease in the levels of total lipids and triglycerides in the liver. Activity of glycerol-3-phosphate dehydrogenase (GPDH), an indicator of triglyceride biosynthesis in white adipose tissue, decreased by 35% in the group supplemented with capsaicin. However, consumption of capsaicin increased the expression of uncoupling protein 2 (UCP2) in white adipose tissue, which is related to energy consumption. Our data suggests that capsaicin may reduce body weight and fat accumulation in high fat diet-induced obese rats. These effects may be mediated, at least partially, by the upregulation of UCP2 gene expression and its ability to inhibit GPDH activity.

Effect of Ginseng Saponin Fraction on Ethanol Metabolism in Rat Liver (인삼사포닌 분획이 동물체(쥐)내에서의 에탄을 대사에 미치는 영향)

  • 곽한식;주충노
    • Journal of Ginseng Research
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    • v.12 no.1
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    • pp.76-86
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    • 1988
  • The rats were fed with 12% ethanol with and/or without 0. l% ginseng saponin instead of water for 6 days, and the acetaldehyde level of liver and serum, and [$NAD^+$]/ [NADH] and [$NADP^+$]/[NADPH] ratios of the liver were investigated. Acetaldehyde level of ethanol fed group (control) in liver and serum was much higher than not-ethanol fed group (normal), but that of ginseng saponin containing ethanol fed group (test) was only slightly higher than that of normal group. Decrease of [$NAD^+$] / (NADH) ratio of test group was also much greater than that of control group. Distribution of the radioactivity in hepatic lipids after the [l-$^{l4}C$]-ethanol feeding intraperitonealy was investigated 30 minutes later. It was found that total radioactivity of the hepatic lipids of test group was much lower than that of control group. Analysis of individual lipids such as phospholipids, cholesterol, fatty acid and triglycerides showed that the depression of phospholipid biosynthesis and increase of fatty acid and triglycerides caused by ethanol feeding were significantly recovered by the co-feeding of ginseng saponin.

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Apolipoprotein H: a novel regulator of fat accumulation in duck myoblasts

  • Ziyi, Pan;Guoqing, Du;Guoyu, Li;Dongsheng, Wu;Xingyong, Chen;Zhaoyu, Geng
    • Journal of Animal Science and Technology
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    • v.64 no.6
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    • pp.1199-1214
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    • 2022
  • Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.

Effect of Oral Administration of Egg Yolk on Cholesterol Metabolism in Rats (난황 경구투여가 랫드의 콜레스테롤 대사에 미치는 영향)

  • Bang, Han-Tae;Hwangbo, Jong;Park, Sang-Oh;Park, Byung-Sung
    • Journal of the Korean Applied Science and Technology
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    • v.31 no.2
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    • pp.255-264
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    • 2014
  • This study was performed to elucidate the biochemical mechanism of metabolism on reducing blood lipid, by oral administration of egg yolk in rats. A total of 36 Sprague Dawley male rats were randomized into four treatment groups, according to a randomized block design. Each group was further divided into three repeat cages, with each repeat cage comprising of 3 rats. The animals were orally administered with egg yolk once a day, while feeding the same purified pellet diet for 6 weeks. The four treatment groups were: C(control, saline 1.0 g), T1(pork belly oil 1.0 g), T2(egg yolk 1.0 g), T3(pork belly oil 1.0 g and egg yolk 1.0 g alternating every week). The measured parameters in each group are listed as follows in the order of highest to the lowest: daily average gain of body weight(T1>T3>T2>C); blood triglyceride and total cholesterol(T1>C>T3>T2) HDL-C (T2>C>T3>T1); and LDL-C (T1>T3>C>T2). AST and ALT, which are the index of liver function, were the highest in T1 but was lowest in T2. The weights of the liver, spleen, and kidney, except for the abdominal fat, showed no significant difference. The weight of abdominal fat was the highest in T1, but there were no significant difference among C, T2, and T3. The HMG-CoA reductase activity was the highest in T1 followed by T3, C but T2 was lowest. The daily fecal excretions of the total sterol, neutral sterol and acid sterol was highest in T2 but lowest in T1. The results of this study show that the egg consumption reduces the blood lipid through facilitation of fecal excretions of sterols and inhibition of enzyme activity in cholesterol biosynthesis, in the liver of animal and human.

Screening of Flavonoid Compounds with HMG-CoA Reductase Inhibitory Activities (플라보노이드 화합물로부터 HMG-CoA reductase 저해 활성 물질 탐색)

  • Son, Kun Ho;Lee, Ju Yeon;Lee, Jeong Soon;Kang, Sam Sik;Sohn, Ho Yong;Kwon, Chong Suk
    • Journal of Life Science
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    • v.28 no.2
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    • pp.247-256
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    • 2018
  • 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used drugs for lowering blood lipid levels and preventing cardiovascular diseases. HMG-CoA reductase is a key enzyme to control the biosynthesis of cholesterol. We have tested HMG-CoA reductase-inhibitory activity on the flavonoids of 98 species in vitro. The anti-hypercholesterolemic activities of flavonoids were studied using an HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance, which represents the oxidation of NADPH by the catalytic subunit of HMG-CoA reductase in the presence of the substrate HMG-CoA. Among the clinically available statins, pravastatin was used as a positive control. Among the tested compounds, kuraridin, morin and sophoraflavanone G showed strong inhibition activities. In particular, morin and sophoraflavanone G inhibited HMG-CoA reductase by 45.0% and 54.6% at a concentration of $10{\mu}g/ml$, and the $IC_{50}$ values were calculated to $13.31{\mu}g/ml$ and $7.26{\mu}g/ml$ respectively.

DNA Polymorphisms in SREBF1 and FASN Genes Affect Fatty Acid Composition in Korean Cattle (Hanwoo)

  • Bhuiyan, M.S.A.;Yu, S.L.;Jeon, J.T.;Yoon, D.;Cho, Y.M.;Park, E.W.;Kim, N.K.;Kim, K.S.;Lee, J.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.6
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    • pp.765-773
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    • 2009
  • Sterol regulatory element binding factor 1 (SREBF1) and fatty acid synthase (FASN) genes play an important role in the biosynthesis of fatty acids and cholesterol, and in lipid metabolism. This study used polymorphisms in the intron 5 of bovine SREBF1 and in the thioesterase (TE) domain of FASN genes to evaluate their associations with beef fatty acid composition. A previously identified 84-bp indel (L: insertion/long type and S: deletion/short type) of the SREBF1 gene in Korean cattle had significant associations with the concentration of stearic (C18:0), linoleic (C18:2) and polyunsaturated fatty acids (PUFA). The stearic acid concentration was 6.30% lower in the SS than the LL genotype (p<0.05), but the linoleic and PUFA contents were 11.06% and 12.20% higher in SS compared to LL (p<0.05). Based on the sequence analysis, five single nucleotide polymorphisms (SNPs) g.17924G>A, g.18043C>T, g.18440G>A, g.18529G>A and g.18663C>T in the TE domain of the FASN gene were identified among the different cattle breeds studied. Among these, only g.17924 G>A and g.18663C>T SNPs were segregating in the Hanwoo population. The g.17924G>A SNP is a non-synonymous mutation (thr2264ala) and was significantly associated with the contents of palmitic (C16:0) and oleic acid (C18:1). The oleic acid concentration was 3.18% and 2.79% higher in Hanwoo with the GG genotype than the AA and AG genotypes, respectively (p<0.05), whereas the GG genotype had 3.8% and 4.01% lower palmitic acid than in those cattle with genotype AA and AG, respectively (p<0.05). Tissue expression data showed that SREBFI and FASN genes were expressed in a variety of tissues though they were expressed preferentially in different muscle tissues. In conclusion, the 84-bp indel of SREBF1 and g.17924G>A SNP of the FASN gene can be used as DNA markers to select Hanwoo breeding stock for fatty acid composition.

Development of Seed Culture Using Soybean for Mass Production of Lovastatin with Aspergillus terreus ATCC 20542 Mutant (대두를 이용한 Lovastatin 대량생산용 Seed Culture의 제조기술)

  • Kim, Soo-Jung;Ko, Hee-Sun;Kim, Hyun-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.37 no.5
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    • pp.666-670
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    • 2008
  • Lovastatin (Mevinolin, Monacolin K) is a well-known drug for the therapy of hypercholesterolemia. It is an important fungal secondary metabolite as it inhibits 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) which catalyzes a major rate-limiting step in the biosynthesis of cholesterol. Both soybeans and black soybeans with Aspergillus terreus ATCC 20542 mutant were used as the seed culture for the mass production of lovastatin. The production of lovastatin in soybean seed culture of Asp. terreus was twofold compared to that of black soybean seed culture. The effect of two different vessels (petri dish and Erlenmeyer flask) on lovastatin production was also studied. The production of lovastatin on petri dish was tenfold to that of Erlenmeyer flask. Furthermore, the most lovastatin production on rice bran was achieved when the soybean seed culture was treated by heat shock at $30^{\circ}C$ for 1 hour, representing 82% of HMG-CoA reductase inhibition in the koji extract. We estimated that the heat treated soybean seed culture could be a new method for the mass production of lovastatin.

Effects of Chitosan Treatment on Changes of Soyasaponin Contents in Soybean Sprouts (키토산 처리가 콩나물의 Soyasaponin 함량변화에 미치는 효과)

  • Oh, Bong-Yun;Park, Bock-Hee;Ham, Kyung-Sik
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.5
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    • pp.584-588
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    • 2007
  • Elicitors are defined as substances that induce defense responses in plants, which include an increased synthesis of secondary metabolites. Saponin, one of the secondary metabolites, has various physiological effects such as anticancer, antioxidant, cholesterol-lowering activities, etc, in human. This study was carried out to find whether a treatment of soybean sprouts with chitosan as an elicitor, increases saponin contents. Saponin contents in soybean sprouts increased by the chitosan treatment during cultivation, reached the peak on the sixth day, and then decreased. A biosynthesis of group B soyasaponin appeared to be regulated differently. The content of soyasaponin I, a member of group B saponin, was the highest in 250 ppm chitosan-treated soybean sprouts, while the contents of soyasaponin II, III and IV were the highest in 1,000 ppm chitosan-treated soybean sprouts. The content of soyasaponin V changed little in soybean sprouts that had been treated with various concentration of chitosan.