HMG-CoA Reductase Inhibition: Anti-Inflammatory Effects beyond Lipid Lowering?

Herz ◽  
2000 ◽  
Vol 25 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Winfried März ◽  
Heinrich Wieland
Keyword(s):  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Anti Inflammatory ◽  
Coa Reductase

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

scholarly journals Crude Ethanol Extract ofPithecellobium ellipticumas a Potential Lipid-Lowering Treatment for Hypercholesterolaemia

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Janet P.-C. Wong ◽  
Sumi Wijaya ◽  
Kang-Nee Ting ◽  
Christophe Wiart ◽  
Kamarul’Ain Mustafa ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
Ethanol Extract ◽  
Beta Carotene ◽  
The Other ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Atherosclerosis Progression ◽  
Bioactive Fraction ◽  
Responsible Group ◽  
Coa Reductase

If left untreated, hypercholesterolaemia can lead to atherosclerosis, given time. Plants from the Fabaceae family have shown the ability to significantly suppress atherosclerosis progression. We selected four extracts fromPithecellobium ellipticum, from the Fabaceae family, to be screened in a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) assay. The ethanol extract, at a concentration of 500 μg/mL, exhibited superior inhibition properties over the other extracts by demonstrating 80.9% inhibition, while 0.223 μg/mL of pravastatin (control) showed 78.1% inhibition towards enzymatic activity. These findings led to the fractionation of the ethanol extract using ethyl acetate : methanol (95 : 5), gradually increasing polarity and produced seven fractions (1A to 7A). Fraction 7A at 150 μg/mL emerged as being the most promising bioactive fraction with 78.7% inhibition. FRAP, beta carotene, and DPPH assays supported the findings from the ethanol extract as it exhibited good overall antioxidant activity. The antioxidant properties have been said to reduce free radicals that are able to oxidize lipoproteins which are the cause of atherosclerosis. Phytochemical screenings revealed the presence of terpenoid, steroid, flavonoid, and phenolic compounds as the responsible group of compound(s), working individually or synergistically, within the extract to prevent binding of HMG-CoA to HMG-CoA reductase.

Atorvastatin in the Treatment of Primary Hypercholesterolemia and Mixed Dyslipidemias

1998 ◽  
Vol 32 (10) ◽  
pp. 1030-1043 ◽  
Author(s):  
Helen S Yee ◽  
Nancy T Fong
Keyword(s):  
Clinical Trials ◽  
Clinical Studies ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Hmg Coa Reductase ◽  
Apo B ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
The Impact

OBJECTIVE: To review the efficacy and safety of atorvastatin in the treatment of dyslipidemias. DATA SOURCES: A MEDLINE search (January 1960–April 1998), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating atorvastatin (i.e., abstracts, clinical trials, proceedings, data on file with the manufacturer) were considered for inclusion. STUDY SELECTION: English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of atorvastatin. Additional relevant citations were used in the introductory material and discussion. DATA EXTRACTION: Open and controlled animal and human clinical studies published in the English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available. DATA SYNTHESIS: Atorvastatin is a recent hydroxymethylglutarylcoenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia, mixed dyslipidemias, and homozygous familial hypercholesterolemia. In patients who have not met the low-density lipoprotein cholesterol (LDL-C) goal as recommended by the National Cholesterol Education Program Adult Treatment Panel II guidelines, atorvastatin 10–80 mg/d may be used as monotherapy or as an adjunct to other lipid-lowering agents and dietary modifications. In placebo-controlled clinical trials, atorvastatin 10–80 mg/d lowered LDL-C by 35–61% and triglyceride (TG) concentrations by 14–45%. In comparative trials, atorvastatin 10–80 mg/d showed a greater reduction of serum total cholesterol (TC), LDL-C, TG concentrations, and apolipoprotein B-100 (apo B) compared with pravastatin, simvastatin, or lovastatin. In comparison, currently available HMG-CoA reductase inhibitors (lovastatin, simvastatin, pravastatin, fluvastatin, cerivastatin) lower LDL-C concentrations by approximately 20–40% and TG concentrations by approximately 10–30%. In pooled placebo-controlled clinical trials of up to a duration of 52 weeks, atorvastatin in dosages up to 80 mg/d appeared to be well tolerated. The most common adverse effect of atorvastatin was gastrointestinal upset. The incidence of elevated serum hepatic transaminases may be greater at higher dosages of atorvastatin. The risk of myopathy and/or rhabdomyolysis is increased when an HMG-CoA reductase inhibitor is taken concomitantly with cyclosporine, gemfibrozil, niacin, erythromycin, or azole antifungals. CONCLUSIONS: Atorvastatin appears to reduce TC, LDL-C, TG concentrations, and apo B to a greater extent than do currently available HMG-CoA reductase inhibitors. Atorvastatin may be preferred in patients requiring greater than a 30% reduction in LDL-C or in patients with both elevated LDL-C and TG concentrations, which may obviate the need for combination lipid-lowering therapy. Adverse effects of atorvastatin appear to be similar to those of other HMG-CoA reductase inhibitors and should be routinely monitored. Long-term safety data (>1 y) on atorvastatin compared with other HMG-CoA reductase inhibitors are still needed. Cost-effectiveness studies comparing atorvastatin with other HMG-CoA reductase inhibitors remain a subject for further investigation. Published clinical studies evaluating the impact of atorvastatin on cardiovascular morbidity and mortality are still needed. Additionally, clinical studies evaluating the impact of lipid-lowering therapy in a larger number of women, the elderly (>70 y), and patients with diabetes for treatment of primary and secondary prevention of coronary heart disease are needed.

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.

Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect

Life Sciences ◽  
2000 ◽  
Vol 67 (8) ◽  
pp. 863-876 ◽  
Author(s):  
Ikuo Inoue ◽  
Sei-ichi Goto ◽  
Kasumi Mizotani ◽  
Takuya Awata ◽  
Toshiyuki Mastunaga ◽  
...  
Keyword(s):  
Reductase Inhibitor ◽  
Hmg Coa Reductase ◽  
Hmg Coa Reductase Inhibitor ◽  
Anti Inflammatory ◽  
Coa Reductase ◽  
Inflammatory Effect

Discovery of a new class of HMG-CoA reductase inhibitor from Polyalthia longifolia as potential lipid lowering agent

2011 ◽  
Vol 46 (10) ◽  
pp. 5206-5211 ◽  
Author(s):  
Koneni V. Sashidhara ◽  
Suriya P. Singh ◽  
Anuj Srivastava ◽  
Anju Puri ◽  
Yashpal S. Chhonker ◽  
...  
Keyword(s):  
Reductase Inhibitor ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
New Class ◽  
Hmg Coa Reductase Inhibitor ◽  
Lipid Lowering Agent ◽  
Coa Reductase ◽  
Polyalthia Longifolia

scholarly journals Lipid Lowering Effects of Hydroalcoholic Extract of Anethum graveolens L. and Dill Tablet in High Cholesterol Fed Hamsters

Cholesterol ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ebrahim Abbasi Oshaghi ◽  
Iraj Khodadadi ◽  
Massoud Saidijam ◽  
Reza Yadegarazari ◽  
Nooshin Shabab ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Profile ◽  
Liver Enzymes ◽  
Lipid Lowering ◽  
High Cholesterol ◽  
Anethum Graveolens ◽  
Hmg Coa Reductase ◽  
Hydroalcoholic Extract ◽  
Coa Reductase ◽  
Group 1

Objective. This study was aimed to determine the effect of Anethum graveolens extract and Anethum graveolens (dill) tablet on lipid profile, liver enzymes, and gene expression and enzymatic activity of HMG-CoA reductase in high cholesterol fed hamsters. Materials and Methods. Golden Syrian male hamsters (130 ± 10 g) were randomly divided into 6 groups (n=6) and received daily the following: group 1 received chow + 2% cholesterol + 0.5% cholic acid (HCD), groups 2 and 3 received HCD diet plus 100 and 200 mg/kg hydroalcoholic extract of dill, respectively, and groups 4 and 5 received HCD diet plus 100 and 200 mg/kg dill tablet, respectively. Group 6 received only chow. After 1 month feeding serum biochemical factors were determined. HMG-CoA reductase mRNA level was measured (real-time PCR) and its activity was determined spectrophotometrically. Results. Compared with hypercholesterolemic group 1, lipid profile, blood glucose, and liver enzymes significantly decreased in all dill tablet or dill extract treated groups (p<0.05). The changes in HMG-CoA reductase gene expression level and enzyme activity significantly reduced in animals that received 200 mg/kg of extract or tablet. Conclusion. Dill extract and dill tablet showed potential hypocholesterolemic properties in hamsters by inhibition of HMG-CoA reductase activity.

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