scholarly journals The Cholesterol-Lowering Effect of Alisol Acetates Based on HMG-CoA Reductase and Its Molecular Mechanism

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Fei Xu ◽  
Hui Yu ◽  
Cai Lu ◽  
Jun Chen ◽  
Wei Gu
Keyword(s):  
Molecular Simulation ◽  
Reductase Activity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Hmg Coa Reductase ◽  
Coa Reductase ◽  
The Impact

This study measured the impact of alisol B 23-acetate and alisol A 24-acetate, the main active ingredients of the traditional Chinese medicine Alismatis rhizoma, on total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) levels of hyperlipidemic mice. The binding of alisol B 23-acetate and alisol A 24-acetate to the key enzyme involved in the metabolism of TC, 3-hydroxy-3-methylglutary-coenzyme A (HMG-CoA) reductase, was studied using the reagent kit method and the western blotting technique combined with a molecular simulation technique. According to the results, alisol acetates significantly lower the TC, TG, and LDL-C concentrations of hyperlipidemic mice, while raising HDL-C concentrations. Alisol acetates lower HMG-CoA reductase activity in a dose-dependent fashion, both in vivo and in vitro. Neither of these alisol acetates significantly lower the protein expression of HMG-CoA. This suggests that alisol acetates lower the TC level via inhibiting the activity of HMG-CoA reductase by its prototype drug, which may exhibit an inhibition effect via directly and competitively binding to HMG-CoA. The side chain of the alisol acetate was the steering group via molecular simulation.

scholarly journals Liver X Receptor Nuclear Receptors Are Transcriptional Regulators of Dendritic Cell Chemotaxis

2018 ◽  
Vol 38 (10) ◽  
Author(s):  
Susana Beceiro ◽  
Attila Pap ◽  
Zsolt Czimmerer ◽  
Tamer Sallam ◽  
Jose A. Guillén ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Low Density Lipoprotein ◽  
Myeloid Cells ◽  
Density Lipoprotein ◽  
Loss Of Function ◽  
Transcriptional Responses ◽  
Cd38 Expression ◽  
The Impact

ABSTRACTThe liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migrationin vitroandin vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR−/−) LDLR−/−mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation.

scholarly journals Cholesterol-Lowering Effects of Lactobacilli and Bifidobacteria Probiotics in vitro and in vivo

2018 ◽  
pp. 1-12
Author(s):  
Shahenda, M. Elaby ◽  
Asmaa A. Salem ◽  
Jehan, B. Ali ◽  
A. F. Abdel-Salam
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Lipoprotein Cholesterol ◽  
Atherogenic Index ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Cholesterol Lowering

Two lactobacilli strains; Lactobacillus acidophilus ATCC 20079 and Lactobacillus plantarum ATCC 20179 and two bifidobacteria strains; Bifidobacterium bifidum GSGG 5286 and Bifidobacterium longum ATCC 15707 were studied their abilities to reduce the cholesterol content in vitro. It was investigated that the in vivo cholesterol-lowering effect of L. plantarum ATCC 20179, B. bifidum GSGG 5286 and mixture of both probiotics (L. plantarum ATCC20179 and B. bifidum GSGG5286) on hyperlipidaemic rats for 8 weeks. All lactobacilli and bifidobacteria strains assimilate the cholesterol content in laboratory media. It was observed the highest assimilation of cholesterol was in L. plantarum ATCC 20179 and B. bifidum GSGG 5286 strains. In vivo, L. plantarum ATCC 20179  group was more effective in improving serum lipid profile levels [total cholesterol (TC), triglycerides (TG), low density lipoprotein – cholesterol (LDL-C), high density lipoprotein – cholesterol                   (HDL-C), very low density lipoprotein – cholesterol (VLDL-C) and Atherogenic Index (AI)],                      liver enzyme activities (ALT, AST and ALP),  malonaldehyde (MDA), hydrogen peroxide (H2O2) and total antioxidants capacity (TAC) levels than mixed-organisms and B. bifidum groups, respectively of hyperlipidaemic rats. It was concluded that L. plantarum ATCC 20179 showed more                     favourable results than B. bifidum GSGG 5286 in relation to cardiovascular risk factors in hyperlipidaemic rats.

Guggulsterone, a farnesoid X receptor antagonist lowers plasma trimethylamine-N-oxide levels: An evidence from in vitro and in vivo studies

2018 ◽  
Vol 38 (3) ◽  
pp. 356-370 ◽  
Author(s):  
A Gautam ◽  
YN Paudel ◽  
SAZ Abidin ◽  
U Bhandari
Keyword(s):  
Hepatic Injury ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Farnesoid X Receptor ◽  
Lipoprotein Cholesterol ◽  
In Vivo Studies ◽  
Low Density Lipoprotein Cholesterol ◽  
Pro Inflammatory Cytokines

The current study investigated the role of guggulsterone (GS), a farnesoid X receptor antagonist, in the choline metabolism and its trimethylamine (TMA)/flavin monooxygenases/trimethylamine- N-oxide (TMAO) inhibiting potential in a series of in vitro and in vivo studies as determined by high-performance liquid chromatography (HPLC), mass spectroscopy (MS), and liquid chromatography (LC)-MS techniques. Atherosclerosis (AS) was successfully induced in a group of experimental animals fed with 2% choline diet for 6 weeks. Serum lipid profiles such as total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were measured. Pro-inflammatory cytokines levels, markers for a hepatic injury, and oxidative stress markers were assessed. Interestingly, GS reduced the level of TMA/TMAO in both in vitro and in vivo studies as demonstrated by the peaks obtained from HPLC, MS, and LC–MS. Furthermore, GS exhibited cardioprotective and antihyperlipidemic effects as evidenced by the attenuation of levels of several serum lipid profiles and different atherogenic risk predictor indexes. GS also prevented hepatic injury by successfully restoring the levels of hepatic injury biomarkers to normal. Similarly, GS inhibited the production of pro-inflammatory cytokines levels, as well as GS, enhanced antioxidant capacity, and reduced lipid peroxidation. Histopathological study of aortic sections demonstrated that GS maintained the normal architecture in AS-induced rats. On the basis of results obtained from current investigation, we suggest that GS might have a great therapeutic potential for the treatment of AS.

In vitro and in vivo cholesterol lowering ability of Lactobacillus pentosus KF923750

2017 ◽  
Vol 8 (2) ◽  
pp. 271-280 ◽  
Author(s):  
F. Bendali ◽  
K. Kerdouche ◽  
S. Hamma-Faradji ◽  
D. Drider
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
Lactobacillus Pentosus ◽  
Survival Percentage

Lactobacillus pentosus KF923750 was characterised for probiotic related properties and then characterised for cholesterol uptake in vitro as well as in vivo using rabbits fed a high-cholesterol diet. The survival percentage of L. pentosus KF923750 was 100% at pH 3, 52.18% at pH 2 and 36.21% at pH 2 plus pepsin. Similarly, this strain appeared resistant to bile (0.1% [98.42%], 0.3% [88.52%], 0.5% [75.60%] and 1% [71.15%]), after 4 h exposure. Moreover, L. pentosus KF923750 controlled growth of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 through the production of a bacteriocin-like inhibitory substance and anti-adhesive capabilities. L. pentosus KF923750 was non-cytotoxic to eukaryotic cells but sensitive to some antibiotics. Compared with rabbits fed a high-cholesterol diet but without L. pentosus KF923750 supplementation, the plasma total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in L. pentosus KF923750-fed rabbits by 11.54, 16.00 and 18.00%, respectively, with no significant change in high-density lipoprotein cholesterol levels. The histological sections of livers revealed lesions in all the rabbits that were fed a high-cholesterol diet, but these were less pronounced in rabbits ingesting L. pentosus KF923750. This study highlights the potential of lactobacilli, such as L. pentosus KF923750, in the treatment or prevention of hypercholesterolemia.

scholarly journals Antihyperlipidemic and Antioxidative Potentials of Onion (Allium cepaL.) Extract Fermented with a NovelLactobacillus caseiHD-010

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Woong-Suk Yang ◽  
Jin-Chul Kim ◽  
Jae Yong Lee ◽  
Cheorl-Ho Kim ◽  
Cher-Won Hwang
Keyword(s):  
Reductase Activity ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Control Group ◽  
Hmg Coa Reductase ◽  
Onion Extract ◽  
Coa Reductase

The purpose of this study was to investigate antihyperlipidemic and antioxidative potentials of onion (Allium cepaL.) extract fermented with a novelLactobacillus caseiHD-010. In general, fermented onion extract is used for its antioxidative activity (ORAC), inhibitory effect on adipocytes differentiation, quercetin contents, and antihyperlipidemic activities. However, the effect of fermented onion extract on hyperlipidemia after oral administration using ApoE-deficient mice has not been reported yet. To understand the effect of fermented onion extract on hyperlipidemia, we used benzafibrate (10 mg/kg, bw/day) as a positive control in the present study. Serum was collected every week to analyze levels of low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG), and cholesterol, 3-hydroxy-3-methylgutaryi-CoA (HMG-CoA) reductase activity, and cholesterol ester transport protein (CETP) activity. In the fermented onion-treated group, HDL level was significantly increased while levels of TG and LDL were significantly decreased compared to those in the control group. In addition, the inhibition activity of HMG-CoA reductase was increased 20% in the fermented onion-treated group at 100 mg/kg. CETP activity has been observed to be significantly inhibited in the fermented onion-treated groups compared to that in the control group. These results suggest that fermented onion has a preventive/therapeutic effect on hyperlipidemic disease. It might have potential to be developed as a functional food.

scholarly journals Effects of compactin, mevalonate and low-density lipoprotein on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity and low-density-lipoprotein-receptor activity in the human hepatoma cell line Hep G2

1984 ◽  
Vol 222 (1) ◽  
pp. 35-39 ◽  
Author(s):  
L H Cohen ◽  
M Griffioen ◽  
L Havekes ◽  
D Schouten ◽  
V van Hinsbergh ◽  
...  
Keyword(s):  
Reductase Activity ◽  
Hepatoma Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hepatoma Cell Line ◽  
Low Density ◽  
Hep G2 ◽  
Human Hepatoma Cell ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Compactin, an inhibitor of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase, decreased cholesterol synthesis in intact Hep G2 cells. However, after the inhibitor was washed away, the HMG-CoA-reductase activity determined in the cell homogenate was found to be increased. Also the high-affinity association of LDL (low-density lipoprotein) to Hep G2 cells was elevated after incubation with compactin. Lipoprotein-depleted serum, present in the incubation medium, potentiated the compactin effect compared with incubation in the presence of human serum albumin. Addition of either mevalonate or LDL prevented the compactin-induced rise in activities of both HMG-CoA reductase and LDL receptor in a comparable manner. It is concluded that in this human hepatoma cell line, as in non-transformed cells, both endogenous mevalonate or mevalonate-derived products and exogenous cholesterol are able to modulate the HMG-CoA reductase activity as well as the LDL-receptor activity.

scholarly journals Bayesian statistic methods and theri application in probabilistic simulation models

2006 ◽  
Vol 7 (1) ◽  
pp. 21-35
Author(s):  
Orietta Zaniolo ◽  
Mario Eandi
Keyword(s):  
Cardiovascular Disease ◽  
Extended Release ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Simulation Models ◽  
Cardiac Events ◽  
Hmg Coa Reductase ◽  
First Line Therapy ◽  
Coa Reductase ◽  
The Impact

Significant advances in the management of hypercholesterolemia have been made possible by the development of statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. More recently, statins have demonstrated benefit in primary and secondary prevention of cardiovascular disease also in patients without hypercholesterolemia. Therefore statins help to reduce the impact of cardiovascular disease on morbility, mortality and social costs. Statins inhibit HMG-CoA reductase competitively, reduce LDL levels more than other cholesterol-lowering drugs, and lower triglyceride levels in hypertriglyceridemic patients. Prescribing statins as first line therapy in management of hypercholesterolemia as a part of a more comprehensive prevention program of cardiovascular disease is widely recommended by international guidelines (e.g. National Cholesterol Education Program - NCEP - Adult Treatment Panel - ATP- III reports). Currently in Italy there are five available statins: atorvastatin, fluvastatin, pravastatin, rosuvastatin and simvastatin; each of them presents some differences in physical and chemical characteristics (solubility), pharmacokinetics (absorption, proteic binding, metabolism and excretion) and pharmacodinamics (pleiotropic effects). Compared to other statins, fluvastatin extended-release (RP) 80 mg provides an equal efficacy in lowering total cholesterol and low-density lipoprotein cholesterol (LDL-C), with an important action on triglyceride (TG) levels and superior increases in HDL-C levels, reducing the incidence of major adverse cardiac events (MACE). Aim of this study is to outline an updated therapeutic and pharmacoeconomic profile of fluvastatin, particularly regarding extended-release (RP) 80 mg formulation.

Lovastatin as a Treatment of Cardiovascular and Neurological Disorders

2019 ◽  
Vol 2 (2) ◽  
Author(s):  
Tursonjan Tokay
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoprotein Cholesterol ◽  
And Migration ◽  
Coa Reductase ◽  
Proliferation And Migration

There is evidence that statins which are mainly used in treatments of dyslipidemia can be used for attenuating symptoms of cardiovascular and neurodegenerative diseases. Lovastatin and other statins are known to function through inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase which is involved in the majority processes such as cell differentiation, proliferation and migration. Recently it was revealed that lovastatin is effective in the reducing total and low-density-lipoprotein cholesterol, lowering the risks of post-surgical complications and mitigation of anticancer drugs’ side effects. Moreover, there are other combinations with other drugs to treat cardiovascular diseases. In addition, antiinflammatory and immunomodulatory effects of lovastatin diminish neurological disorders such as multiple sclerosis (MS). Especially, combination treatment of lovastatin and rolipram in suboptimal doses is considered to be the most promising approach for protecting neuronal axons from demyelination and promoting neuro repair in MS. Although lovastatin demonstrates promising option for treatment of cardiovascular and neurological diseases, more clinical trials and studies in vivo and in vitro are required.

scholarly journals Novel Phytoconstituents of an Aqueous Pod Extract of Prosopis Cineraria (L.) Druce Attenuate Atherosclerotic Plaque and Hypercholesterolemia in Rabbits

2020 ◽  
Author(s):  
Heera Ram ◽  
Noopur Jaipal ◽  
Pramod Kumar ◽  
Jaykaran Charan ◽  
Priya Kashyap ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
In Silico ◽  
Reductase Activity ◽  
Hmg Coa Reductase ◽  
Prosopis Cineraria ◽  
Oral Supplementation ◽  
Coa Reductase ◽  
Leading Compounds

Abstract Background and objectives: The pod of Prosopis cineraria traditionally used in several ailments and key component of traditional food recipe of the Panchkuta of western Rajasthan, India. The current study was targeted to assess ability of phytoconstituents of aqueous pod extract of Prosopis cineraria to inhibit HMG-CoA reductase activity and regress atherosclerotic plaque were investigated in in-vitro, in-vivo, and in-silico studies. Material and Methods: LCMS, GCMS, and FTIR analysis were used to characterize the phytoconstituents of the test extract. Accordingly, the in-vitro, in-vivo and in-silico assessments were performed by following the standard methods. Results: The phytochemical results shown the presence of cloprostenol, cinecromen, and dirithromycin as leading compounds. Accordingly, in-vivo assay of test extract shown HMG-CoA inhibition activity by 78.1 % (IC50 was 0.03 μg/ml). Hypercholesterolemia was induced in rabbits through oral supplementation of a high fat diet (21 % fat) with cholesterol powder supplementation. Administration of the test extract caused significant (𝑃 ≤ 0.001) improvement in the lipid profile and antioxidant levels in the test rabbits, relative to the hypercholesterolemic control rabbits. Subsequently, the reductions in the atherosclerotic plaque and improvement in lumen volume were pointedly observed in the treated groups. In-silico analyses of molecular docking and ADMET revealed significant interactions and druggability profile. Conclusion: It can be stated that the phytoconstituents of aqueous pod extract of Prosopis cineraria have the capacity to inhibit HMG-CoA reductase and regress the atherosclerotic plaque which may be beneficial to the treatment of hypercholesterolemia.

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