Faecal sterol output is increased by arachidyl amido cholanoic acid (Aramchol) in rats

2004 ◽  
Vol 32 (1) ◽  
pp. 131-133 ◽  
Author(s):  
A. Leikin-Frenkel ◽  
A.A Weinbroum ◽  
D. Leikin-Gobbi ◽  
L. Krupitzky ◽  
I. Goldiner ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Reductase Activity ◽  
Human Fibroblasts ◽  
Biliary Lipid ◽  
Short Term ◽  
Cholesterol Levels ◽  
Atp Binding Cassette Transporter ◽  
Coa Reductase ◽  
Dependent Pathway ◽  
Cholanoic Acid

Fatty acid–bile acid conjugates (FABACs) were shown recently to have important and multiple effects on cholesterol metabolism. In human fibroblasts, they were found to markedly enhance cholesterol efflux by an ATP-binding cassette transporter A1-dependent pathway. In C57L/J mice, they increased CYP7A1 activity and RNA expression, while decreasing moderately 3-hydroxy-3-methylglutaryl-CoA reductase activity. In C57L/J mice and in hamsters, they also decreased serum cholesterol levels, whereas in other animals, this effect was not seen in short-term experiments. In the present study, we investigated potential mechanisms of action of arachidyl amido cholanoic acid (Aramchol), with particular reference to biliary and faecal sterol outputs in rats. Supplementation with Aramchol at a dose of 150 mg·kg−1·day−1 increased neutral sterol output by approx. 50%, while the faecal outputs of bile salts and total sterols increased by almost 2-fold. Biliary lipid outputs were not significantly different between the control and FABAC-supplemented animals. These findings indicate an overall catabolic effect of FABACs on body cholesterol.

Cholesterol metabolism in obese mice

1980 ◽  
Vol 58 (11) ◽  
pp. 1258-1260 ◽  
Author(s):  
Peter Hahn
Keyword(s):  
Adipose Tissue ◽  
Cholesterol Metabolism ◽  
Reductase Activity ◽  
Young Male ◽  
Blood Cholesterol ◽  
Obese Mice ◽  
Cholesterol Levels ◽  
Brown Adipose ◽  
Coa Reductase ◽  
White Fat

Young male obese mice and their lean litter mates (strain ob/ob) were compared. Serum cholesterol levels were higher in obese than in lean animals. 3-Hydroxy-3-methylglutaryl-CoA reductase activity was lower in brown adipose tissue and liver of obese mice than in tissue from their lean litter mates. However, activity of this enzyme was found to be the same or higher in white adipose tissue of obese animals than in their lean litter mates. During complete starvation, blood cholesterol levels in obese mice decreased and attained the lower level of lean ones after 48 h. After 24 h of starvation, enzyme activity decreased in white fat of obese mice only. Simple calculations indicate that white fat from obese mice produces about fourfold more cholesterol per day per unit body weight than does the same tissue from lean mice.

Interactive Effect of Hesperidin and Vitamin E Supplements on Cholesterol Metabolism in High Cholesterol-Fed Rats

2001 ◽  
Vol 71 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Yong Bok Park ◽  
Kyung-Min Do ◽  
Song-Hae Bok ◽  
Mi-Kyung Lee ◽  
Tae-Sook Jeong ◽  
...  
Keyword(s):  
Vitamin E ◽  
Cholesterol Metabolism ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Interactive Effect ◽  
Free Groups ◽  
Dietary Vitamin ◽  
High Cholesterol ◽  
Triglyceride Content ◽  
Coa Reductase

Certain bioflavonoids are potent antioxidants and have pharmacologic effects similar to those of vitamin E. Accordingly, the interactive effect of hesperidin and vitamin E was studied with respect to cholesterol metabolism and the antioxidant status. Hesperidin supplement (0.1%, wt/wt) with comparable levels of vitamin E was provided with a high-cholesterol (1%, wt/wt) diet to rats for 5 weeks. The amount of vitamin E included in the hesperidin-free and hesperidin diets was either a low (low-E) or a normal (normal-E) level. The hesperidin supplement and different levels of dietary vitamin E did not significantly alter the concentrations of plasma triglycerides. However, the inclusion of hesperidin significantly lowered the concentration of plasma cholesterol in both the low-vitamin E group and the normal-vitamin E group compared to the hesperidin-free groups (p < 0.05). The hepatic triglyceride content was significantly lowered by the hesperidin supplement, as opposed to the plasma triglyceride content, regardless of the vitamin E level in the diet. The hepatic HMG-CoA reductase activity was significantly lowered by the hesperidin supplement with both the low-vitamin E and the normal-vitamin E compared to the hesperidin-free groups (p < 0.05). The hepatic HMG-CoA reductase activity was also significantly lowered with an increase in the dietary vitamin E within the hesperidin and hesperidin-free groups. The excretion of fecal neutral sterol and acidic sterols tended to be lower with the hesperidin supplement. Neither dietary hesperidin nor vitamin E significantly changed the hepatic antioxidant enzyme activity. This data indicates that hesperidin lowers the concentration of plasma cholesterol and the hepatic triglyceride content regardless of the dietary vitamin E level. However, the concentration of plasma cholesterol in the hesperidin-free groups was dependent on the dietary vitamin E level. This information may contribute to understanding the interactive effect of hesperidin and vitamin E on cholesterol biosynthesis in high cholesterol-fed rats.

scholarly journals Inhibition of HMG-CoA Reductase Activity from Active Compounds of Ginger (Zingiber officinale): In-Silico Study

2021 ◽  
Vol 1 (1) ◽  
pp. 32-38
Author(s):  
Rosario Trijuliamos Manalu ◽  
Imelia Omega Meheda ◽  
Cintya Octaviani
Keyword(s):  
In Silico ◽  
Cholesterol Metabolism ◽  
Raw Materials ◽  
Reductase Activity ◽  
Zingiber Officinale ◽  
Active Compounds ◽  
Hmg Coa Reductase ◽  
Conducting Research ◽  
Main Components ◽  
Coa Reductase

ABSTRAK   Koleterol merupakan salah satu dari lemak tubuh dalam asam lemak bebas dan ester, yang termasuk komponen utama selaput sel otak dan saraf. Namun, tidak jarang kolesterol menjadi penyebab penyakit terutama penyakit jantung yang terus meningkat setiap tahunnya di Indonesia. Sehingga perlu strategi pengobatan yang efektif dan aman dengan melakukan penelitian tanaman Indonesia sebagai upaya kemandirian bahan baku obat. Tujuan dari penelitian ini adalah untuk menentukan aktivitas penghambatan dari senyawa aktif tanaman Jahe pada HMG-KoA reduktase secara in-silico melalui penambatan molekul. Senyawa aktif yang digunakan dalam penelitian ini curcumin, capsaisin, gingerol, paradol, shogaol dilakukan docking molekuler menggunakan software PLANTS dengan tujuan untuk mengetahui score docking dan interaksi kelima senyawa terhadap enzim HMG-KoA reduktase yang berperan terhadap metabolism lemak/kolesterol. Senyawa pembanding yang digunakan adalah simvastatin dan atorvastatin yang merupakan obat lini pertama untuk pengobatan displipidemia. Hasil score docking menunjukkan bahwa kelima senyawa aktif yang digunakan sebagai ligan, menunjukkan score docking yang lebih rendah dibandingkan dengan ligan pembanding, sehingga kelima senyawa aktif ini mampu untuk menghambat biosintesis kolesterol atau kandidat obat baru pengganti simvastatin dan atorvastatin serta berpotensi sebagai dyslipidemia.   ABSTRACT Cholesterol is one of the body's fats in free fatty acids and esters, which are the main components of brain and nerve cell membranes. However, it is not uncommon for cholesterol to be the cause of disease, especially heart disease, which continues to increase every year in Indonesia. So it needs an effective and safe treatment strategy by conducting research on Indonesian plants as an effort to be independent of medicinal raw materials. The aim of this study was to determine the inhibitory activity of the active compound of Ginger plant on HMG-CoA reductase in-silico through molecular anchoring. The active compounds used in this study were curcumin, capsaicin, gingerol, paradol, shogaol. Molecular docking was carried out using PLANTS software with the aim of knowing the docking score and the interaction of the five compounds with the HMG-CoA reductase enzyme that plays a role in fat/cholesterol metabolism. Comparative compounds used are simvastatin and atorvastatin which are first-line drugs for the treatment of dysplipidemia.  

scholarly journals Bioactive Pigments of Monascus purpureus Attributed to Antioxidant, HMG-CoA Reductase Inhibition and Anti-atherogenic Functions

2021 ◽  
Vol 5 ◽  
Author(s):  
H. P. Mohankumari ◽  
K. Akhilender Naidu ◽  
K. Narasimhamurthy ◽  
G. Vijayalakshmi
Keyword(s):  
Reductase Activity ◽  
Lipid Peroxide ◽  
Hdl Cholesterol ◽  
Monascus Purpureus ◽  
Bioactive Metabolites ◽  
Hmg Coa Reductase ◽  
Cholesterol Levels ◽  
Atherogenic Indices ◽  
Coa Reductase

Monascus purpureus is known to produce pigment molecules. The pigments were extracted from M. purpureus fermented rice. In-vitro antioxidant effects of pigments were observed and presumed to alleviate oxidative stress related atherosclerosis effect in rats fed with high fat diet (HFD) for 14 weeks. The formation of lipid peroxide due to the oxidation of serum lipid was higher in rats fed with HFD. While, the feeding of fermented rice (groups III-V) significantly lowered the formation of lipid peroxide (27.1–51.7%) in serum of rats, indicated antioxidative effect of pigments. In addition, feeding of fermented rice lowered serum cholesterol and triacylglycerol by 44.82 and 45.30%, respectively. Whereas, LDL-cholesterol levels were decreased by 70.12% and HDL-cholesterol increased by 34.58%. The atherogenic indices (LDL/HDL and TC/HDL) were reduced by 77.80 and 61.05%, respectively, in rats fed with fermented rice. These data confirmed the anti-atherosclerotic effect of pigments. Further liver enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was significantly inhibited up to 54%. The identification of statins, sterols and fatty acids in fermented rice revealed the HMG-CoA reductase inhibitory activity. This was confirmed by synthesis of lower levels of cholesterol and triacylglycerol in liver of rats fed with fermented rice. Accordingly antioxidant, inhibition of HMG-CoA reductase, anti-atherogenic functions of M. purpureus fermented rice is attributed to the collective effect of bioactive metabolites.

HMG-CoA reductase inhibitor attenuates platelet adhesion in intestinal venules of hypercholesterolemic mice

2004 ◽  
Vol 286 (4) ◽  
pp. H1402-H1407 ◽  
Author(s):  
Anitaben Tailor ◽  
David J. Lefer ◽  
D. Neil Granger
Keyword(s):  
Cell Adhesion ◽  
Protective Effect ◽  
Vascular Wall ◽  
Normal Diet ◽  
Wild Type ◽  
Short Term ◽  
Cholesterol Levels ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase ◽  
Adhesion Of Platelets

Whereas the anti-inflammatory properties of statins have been extensively studied, less attention has been devoted to the antithrombogenic effects of these drugs. We evaluated the effect of short-term (18 h) treatment with pravastatin (1 mg/kg) on hypercholesterolemia-induced platelet-endothelial (P/E) cell adhesion in intestinal venules. Mice were placed on either a normal diet (ND) or cholesterol-enriched diet (HCD) for 2 wk. Wild-type mice fed a HCD exhibited significantly elevated blood serum cholesterol levels, which were unaltered by pravastatin treatment. ND or HCD platelets were isolated, fluorescently labeled, and administered to either ND or HCD recipients. Intravital videomicroscopy was used to quantify transient (saltation) and firm adhesion of platelets. HCD mice receiving platelets from either ND or HCD mice exhibited increased P/E cell interactions compared with ND mice receiving platelets from ND or HCD mice. P/E adhesion was dramatically reduced when platelets from donor mice, recipient mice, or both were treated with pravastatin. The protective effect of pravastatin in hypercholesterolemia-induced P/E cell adhesion was abolished in NG-nitro-l-arginine methyl ester-treated mice. These results indicate that 1) hypercholesterolemia-induced P/E cell adhesion is mediated by changes in the vascular wall rather than circulating platelets; 2) pravastatin treatment inhibits the prothrombogenic effects of hypercholesterolemia via an action on both endothelial cells and platelets; and 3) the protective effect of pravastatin is nitric oxide dependent.

Short-term effects of ACTH on the low-density lipoprotein receptor mRNA level in rat and hamster adrenals

1991 ◽  
Vol 6 (3) ◽  
pp. 223-230 ◽  
Author(s):  
J.-G. Lehoux ◽  
A. Lefebvre
Keyword(s):  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Low Density ◽  
Short Term ◽  
Hmg Coa Reductase ◽  
Receptor Mrna ◽  
Coa Reductase

ABSTRACT Low-density lipoprotein (LDL) receptor mRNA was found in both rat and hamster adrenals. Within 30 min after ACTH administration a significant increase in the levels of both LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) mRNAs was observed in rat adrenals; these levels remained increased for up to 240 min. The increase in the levels of LDL receptor and HMG-CoA reductase mRNAs produced by ACTH was reduced by co-administration of aminoglutethimide while, at the same time, the adrenal cholesterol content of rats treated with both aminoglutethimide and ACTH was significantly increased compared with that in groups treated with ACTH alone. Cycloheximide also induced increased levels of rat adrenal mRNAs for LDL receptor and HMG-CoA reductase, but this effect was not additive with that of ACTH. These results suggest that, in the rat, the short-term effect of ACTH on the levels of mRNAs for the LDL receptor and HMG-CoA reductase is similarly controlled and might be mediated through changes in the adrenal cholesterol content. In the hamster adrenal, however, no significant fluctuations were found in the level of LDL receptor mRNA, although a marked increase was found in the level of HMG-CoA reductase mRNA, 2 h after ACTH administration. This indicates that an important effect of ACTH on cholesterol metabolism in the hamster adrenal is at the level of HMG-CoA reductase. In the hamster, therefore, where the main source of cholesterol for the adrenal gland is de-novo synthesis, it seems that a complex mechanism is involved in the control of LDL receptor gene expression.

scholarly journals Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model

2016 ◽  
Vol 5 ◽  
Author(s):  
Haiqiu Huang ◽  
Zhuohong Xie ◽  
Wallace Yokoyama ◽  
Liangli Yu ◽  
Thomas T. Y. Wang
Keyword(s):  
High Fat Diet ◽  
Cholesterol Metabolism ◽  
Ldl Receptor ◽  
High Fat ◽  
Hamster Model ◽  
Hmg Coa Reductase ◽  
Cholesterol Levels ◽  
Reductase Mrna ◽  
Coa Reductase ◽  
The Relationship

AbstractHypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia.

Regulation of Short-Term Changes in Hepatic β-Hydroxy-β-methylglutaryl-CoA Reductase Activity

1982 ◽  
Vol 125 (3) ◽  
pp. 497-503 ◽  
Author(s):  
Richard E. DUGAN ◽  
Terry A. BAKER ◽  
John W. PORTER
Keyword(s):  
Reductase Activity ◽  
Short Term ◽  
Coa Reductase

scholarly journals Beta-Arrestin 1 Mediates Liver Thyrotropin Regulation of Cholesterol Conversion Metabolism via the Akt-Dependent Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Shaona Niu ◽  
Hui Li ◽  
Wenbin Chen ◽  
Jiajun Zhao ◽  
Ling Gao ◽  
...  
Keyword(s):  
Cholesterol Metabolism ◽  
Inhibitory Effect ◽  
Thyroid Stimulating Hormone ◽  
G Protein Coupled Receptors ◽  
Akt Phosphorylation ◽  
Cholesterol Levels ◽  
Second Wave ◽  
G Protein Coupled ◽  
Dependent Pathway

After activation, G protein-coupled receptors (GPCRs) are desensitized by β-arrestins (ARRBs). Moreover, ARRBs can initiate a second wave of signaling independent of G proteins. Thyroid-stimulating hormone receptor (TSHR) is one of the GPCR members. In our previous study, TSHR was identified in the liver; the major role of TSHR in cholesterol metabolism was illustrated, as TSH could regulate hepatic cholesterol metabolism via cAMP/PKA/CREB/HMGCR and SREBP2/HNF4α/CYP7A1 pathways. It has been reported that ARRB2 predominates over ARRB1 in TSHR internalization. However, the significance of ARRBs in TSH-initiated cholesterol metabolism has not been illustrated. In our study, the effects of ARRBs on TSH-regulated cholesterol metabolism are investigated. ARRB1/2 was genetically inactivated in C57BL/6 mice and HepG2 cell line, respectively. Cholesterol levels in arrestin-knockout mice and arrestin-knockdown cells were measured. Molecules participating in cholesterol metabolism were analyzed. It turned out that deficiencies in ARRB1 led to decreased cholesterol levels and decreased TSH-stimulated AKT phosphorylation. Subsequently, the inhibitory effect on CYP7A1 by SREBP2 was reduced due to lowered mature SREBP2 level. Other than the failures of TSH in ARRB-knockdown cells, the AKT activator SC79 could enhance AKT phosphorylation and mature SREBP2 level. Our results demonstrate that ARRBs, especially ARRB1, are involved in TSH-regulated cholesterol metabolism through the AKT pathway.

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