scholarly journals Inhibition of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (Ex Vivo) by Morus indica (Mulberry)

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Vanitha Reddy Palvai ◽  
Asna Urooj
Keyword(s):  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Ex Vivo ◽  
Plasma Cholesterol ◽  
Effective Means ◽  
Inhibitory Effect ◽  
Hmg Coa Reductase ◽  
Standard Drug ◽  
Coa Reductase

Phytochemicals are the bioactive components that contribute to the prevention of cardiovascular and other degenerative diseases. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase would be an effective means of lowering plasma cholesterol in humans. The present study explores the HMG CoA reductase inhibitory effect of extracts from leaves of Morus indica varieties, M5, V1, and S36, compared with the statin, using an ex vivo method. The assay is based on the stoichiometric formation of coenzyme A during the reduction of microsomal HMG CoA to mevalonate. Dechlorophyllised extract of three varieties was studied at 300 µg. The coenzyme A released at the end of assay in control (100.31 nmoles) and statins (94.46 nm) was higher than the dechlorphyllised extracts of the samples. The coenzyme A released during the reduction of HMG CoA to mevalonate in dechlorophyllised extracts of the samples was as follows: S36 < M5 < V1. The results indicated that the samples were highly effective in inhibiting the enzyme compared to statins (standard drug). The results indicate the role of Morus varieties extracts in modulating the cholesterol metabolism by inhibiting the activity of HMG CoA reductase. These results provide scope for designing in vivo animal studies to confirm their effect.

scholarly journals Anti-HMG-CoA Reductase, Antioxidant, and Anti-Inflammatory Activities ofAmaranthus viridisLeaf Extract as a Potential Treatment for Hypercholesterolemia

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Shamala Salvamani ◽  
Baskaran Gunasekaran ◽  
Mohd Yunus Shukor ◽  
Noor Azmi Shaharuddin ◽  
Mohd Khalizan Sabullah ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Cholesterol Metabolism ◽  
Inhibitory Effect ◽  
Hmg Coa Reductase ◽  
Synthetic Drugs ◽  
Reductase Inhibitors ◽  
Plot Analysis ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Coa Reductase

Inflammation and oxidative stress are believed to contribute to the pathology of several chronic diseases including hypercholesterolemia (elevated levels of cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant origin are needed as synthetic drugs, such as statins, which are known to cause adverse effects on the liver and muscles.Amaranthus viridis(A. viridis) has been used from ancient times for its supposedly medically beneficial properties. In the current study, different parts ofA. viridis(leaf, stem, and seed) were evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities. The putative HMG-CoA reductase inhibitory activity ofA. viridisextracts at different concentrations was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate.A. viridisleaf extract revealed the highest HMG-CoA reductase inhibitory effect at about 71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations.A. viridisleaf extract was proven to be an effective inhibitor of hyaluronidase, lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest thatA. viridisleaf extract is a source of potent antioxidant and anti-inflammatory agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase.

scholarly journals The Promoter of the Rat 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Contains a Tissue-Specific Estrogen-Responsive Region

1999 ◽  
Vol 13 (8) ◽  
pp. 1225-1236 ◽  
Author(s):  
Luciano Di Croce ◽  
Guillermo P. Vicent ◽  
Adali Pecci ◽  
Giovannella Bruscalupi ◽  
Anna Trentalance ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cell Lines ◽  
Coenzyme A ◽  
Cholesterol Metabolism ◽  
Hmg Coa Reductase ◽  
Tissue Specific ◽  
Reductase Gene ◽  
Responsive Element ◽  
Coa Reductase ◽  
Mcf 7

Abstract The isoprenoid metabolic pathway is mainly regulated at the level of conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) to mevalonate, catalyzed by HMG CoA reductase. As estrogens are known to influence cholesterol metabolism, we have explored the potential regulation of the HMG CoA reductase gene promoter by estrogens. The promoter contains an estrogen-responsive element-like sequence at position −93 (termed Red-ERE), which differs from the ERE consensus by one mismatch in each half of the palindrome. A Red-ERE oligonucleotide specifically bound estrogen receptor in vitro and conferred receptor-dependent estrogen responsiveness to a heterologous promoter in all cell lines tested. However, expression of a reporter driven by the rat HMG CoA reductase promoter was induced by estrogen treatment after transient transfection into the breast cancer cell line MCF-7 cells but not in hepatic cell lines expressing estrogen receptor. Estrogen induction in MCF-7 cells was dependent on the Red-ERE and was strongly inhibited by the antiestrogen ICI 164,384. A functional cAMP-responsive element is located immediately upstream of the Red-ERE, but cAMP and estrogens inhibit each other in terms of transactivation of the promoter. Similarly, induction by estrogens was inhibited by micromolar concentrations of cholesterol, likely acting via changes in occupancy of the sterol-responsive element located 70 bp upstream of the Red-ERE. Thus, within its natural context, Red-ERE is able to mediate hormonal regulation of the HMG CoA reductase gene in tissues that respond to estrogens with enhanced cell proliferation, while it is not operative in liver cells. We postulate that this tissue-specific regulation of HMG CoA reductase by estrogens could partially explain the protective effect of estrogens against heart disease.

Posttranslational Regulation of HMG CoA Reductase, the Rate-Limiting Enzyme in Synthesis of Cholesterol

2021 ◽  
Vol 90 (1) ◽  
pp. 659-679
Author(s):  
Marc M. Schumacher ◽  
Russell A. DeBose-Boyd
Keyword(s):  
Endoplasmic Reticulum ◽  
Cholesterol Metabolism ◽  
Posttranslational Regulation ◽  
Hmg Coa Reductase ◽  
Feedback Mechanisms ◽  
Genetically Manipulated ◽  
Coa Reductase ◽  
Rate Limiting

The polytopic, endoplasmic reticulum (ER) membrane protein 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate, the key intermediate in the synthesis of cholesterol and many nonsterol isoprenoids including geranylgeranyl pyrophosphate (GGpp). Transcriptional, translational, and posttranslational feedback mechanisms converge on this reductase to ensure cells maintain a sufficient supply of essential nonsterol isoprenoids but avoid overaccumulation of cholesterol and other sterols. The focus of this review is mechanisms for the posttranslational regulation of HMG CoA reductase, which include sterol-accelerated ubiquitination and ER-associated degradation (ERAD) that is augmented by GGpp. We discuss how GGpp-induced ER-to-Golgi trafficking of the vitamin K2 synthetic enzyme UbiA prenyltransferase domain–containing protein-1 (UBIAD1) modulates HMG CoA reductase ERAD to balance the synthesis of sterol and nonsterol isoprenoids. We also summarize the characterization of genetically manipulated mice, which established that sterol-accelerated, UBIAD1-modulated ERAD plays a major role in regulation of HMG CoA reductase and cholesterol metabolism in vivo.

scholarly journals Solubility and Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin:In Vitro,Ex Vivo, andIn VivoStudies

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Madhuri S. Rodde ◽  
Ganesh T. Divase ◽  
Tejas B. Devkar ◽  
Avinash R. Tekade
Keyword(s):  
Drug Release ◽  
Dissolution Rate ◽  
Ex Vivo ◽  
Reductase Activity ◽  
Polymer Concentration ◽  
Water Soluble ◽  
Hmg Coa Reductase ◽  
Coa Reductase

The objective of this investigation was to improve the solubility of the poorly water soluble drug atorvastatin (ATR), using solid dispersion (SD) techniques, with Neem Gum (NG) as a hydrophilic carrier. The effects of the polymer concentration and method of preparation on the solubility and dissolution rate were studied. The results showed that the solubility of ATR increases with increasing NG concentration. However, dissolution rate of ATR from its SD was dependent on the method used to prepare SD. Anin vitrodrug release study revealed that the solvent evaporation technique is a more convenient and effective method of preparing SD than kneading method. The SD was characterized using DSC, SEM, and XRD study. Anin vivostudy was performed in which the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibition activity was measured. A significant reduction in HMG CoA reductase activity was observed with SD of ATR compared with the plain drug. Anex vivoabsorption study was carried out using modified apparatus developed in our laboratory. Thein vitrodrug release andin vivoandex vivostudies clearly demonstrated the potential of hydrophilic NG in enhancing the solubility, dissolution rate, and bioavailability of ATR.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

In Vivo LDL Receptor and HMG-CoA Reductase Regulation in Human Lymphocytes and Its Alterations During Aging

1995 ◽  
Vol 15 (7) ◽  
pp. 872-878 ◽  
Author(s):  
Thomas M. Stulnig ◽  
Helmut Klocker ◽  
H. James Harwood ◽  
Günther Jürgens ◽  
Dieter Schönitzer ◽  
...  
Keyword(s):  
Human Lymphocytes ◽  
Ldl Receptor ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Assessment of Antithrombotic Properties of Sodium Ibuprofen

1982 ◽  
Vol 48 (01) ◽  
pp. 087-090 ◽  
Author(s):  
Carlos O Esquivel ◽  
David Bergqvist ◽  
Claes-Göran Björck ◽  
Stan N Carson ◽  
Bodil Nilsson
Keyword(s):  
Drug Administration ◽  
Platelet Function ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Formation Time ◽  
Platelet Activity ◽  
Laser Injury ◽  
Sodium Ibuprofen ◽  
Plug Formation

SummaryThe effect of sodium ibuprofen on platelet activity in vivo and the lysability of ex vivo thrombi was investigated. The formation of a hemostatic platelet plug in the rabbit mesentery and platelet embolism as a response to a laser-induced injury in the ear chamber of rabbits were used as models for determining platelet activity. Ibuprofen at a dose of 25 mg/kg i.v. was found to increase the primary (PHT) and the total hemostatic plug formation time (THT). The same dose decreased the number of cumulative emboli over a 10 min period after a laser injury to arterioles. A dose of 10 mg/kg i.v. did not affect the formation of the hemostatic platelet plug. In dogs, doses of 10, 25 und 50 mg/kg did not enhance the release of 125I-FDP from the thrombi after incubation in plasmin, but the largest dose which is approximately five times the recommended dose in humans, did significantly decrease the thrombus weight 90 and 180 min after the drug administration. In conclusion, sodium ibuprofen was shown to have an inhibitory effect on platelet function in vivo and in large doses was also found to diminish the thrombus weight.

scholarly journals Circulating Markers Reflect Both Anti- and Pro-Atherogenic Drug Effects in ApoE-Deficient Mice

2008 ◽  
Vol 3 ◽  
pp. BMI.S632 ◽  
Author(s):  
Birong Liao ◽  
Eileen McCall ◽  
Karen Cox ◽  
Chung-Wein Lee ◽  
Shuguang Huang ◽  
...  
Keyword(s):  
Whole Blood ◽  
Plasma Cholesterol ◽  
Drug Effects ◽  
Drug Efficacy ◽  
Vascular Wall ◽  
Atherosclerotic Plaques ◽  
Protein Markers ◽  
Novel Approach ◽  
Coa Reductase

Background Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol. Results ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis. Conclusion In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems.

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