Simvastatin

OBJECTIVE: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. METHODS: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group)...

Activation of RhoA and Rho-associated kinases (ROCKs) is known to play a pivotal role in the regulation of smooth muscle contraction via phosphorylation of myosin-light chain and myosin phosphatase. There are few data on the RhoA and ROCKs expression levels in rat uteri. Therefore, our aim was to investigate the mRNA and protein concentration of RhoA and ROCKs in rat uterus during pregnancy, during parturition and post-partum using real time PCR and Western blot analysis. The other purpose was to evaluate the effects of the ROCK (Y-27632, fasudil and RKI 1441) and RhoA inhibitors (simvastatin) on uterine contractility in isolated organ bath experiments...

Xanthohumol, a prenylated flavonoid found in hops (Humulus lupulus L.), exhibits multiple biological activities such as anti-atherosclerosis and hypolipidemic activities. In this study, we aim to investigate the hypocholesterolemic effects and molecular mechanisms of xanthohumol in hepatic cells. We found that xanthohumol (10 and 20 μM) increased the amount of cell-surface low-density lipoprotein receptor (LDLR) from 100.0 ± 2.1% to 115.0±1.3% and 135.2±2.7%, and enhanced the LDL uptake activity from 100...

PURPOSE: This nested case-control study aimed to evaluate the association of candidate genetic variants with statin-induced myotoxicity in Chinese patients with coronary artery disease (CAD). METHODS: One hundred forty-eight Chinese patients experiencing statin-induced myotoxicity were included in our study, and 255 patients without muscular side effects served as controls. Five SNPs in CYP3A5, SLCO1B1, and APOE were genotyped. The effect of genetic variants on statin-induced myotoxicity was assessed...

OBJECTIVES: Usnea is a lichen of Usnea diffracta Vain and Usnea longissima Ach, which belongs to the genus Usnea Adans of Usneaceae. Usnea exerts numerous pharmacological activities, while its lipid regulatory activities remain unreported. This study aims to evaluate the effects of aqueous and ethanol extracts of Usnea on the regulation of lipid metabolism and to explore the possible mechanism. METHODS: Hyperlipidemia rat model was established by feeding with high-fat diet for 45days...

Matrix metalloproteinase-9 (MMP-9) is dysregulated in chronic kidney diseases including diabetic nephropathy. This study was performed to examine the expression of MMP-9 in renal tubule epithelial cells (TECs) under diabetic conditions and its regulatory mechanisms. We characterized MMP-9 protein in diabetic animals and primary cultured rat TECs exposed to exogenous albumin and high glucose. We also used specific inhibitors to determine if internalization of albumin and/or extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation were required for MMP-9 secretion...

In this study, our results showed that the c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1) and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways...

BACKGROUND: Lipoprotein(a) [Lp(a)] is an inherited atherogenic lipoprotein and an independent risk factor for atherosclerotic cardiovascular disease; however, its clinical role remains limited. OBJECTIVE: We hypothesized that Lp(a) screening in high cardiovascular risk patients could provide insight into disease pathogenesis and modify physician behavior for treatment intensification targeting traditional risk factors when Lp(a)-related risk was identified. METHODS: We screened 113 patients presenting electively for percutaneous coronary intervention (PCI) for Lp(a) who met any of the following criteria: (1) premature coronary artery disease (male age <55 years, female age <65 years); (2) family history of premature coronary artery disease; (3) progression to PCI despite well-controlled traditional risk factors (blood pressure <140/90 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL, and HbA1c <7%, and nonsmoker); or (4) progression to PCI despite at least moderate intensity statin use (simvastatin 40, atorvastatin 40-80, or rosuvastatin 20-40 mg daily)...

Many patients with sepsis died of heart failure caused by sepsis-induced myocardial depression. Patients with cardiovascular diseases treated by statins have a lower incidence and mortality of sepsis, although the mechanisms remain elusive. To investigate the protective effect of simvastatin on sepsis-induced myocardial depression and to explore possible mechanisms of action. Thirty six adult male Wistar rats were pretreated with simvastatin (0.2μg/g, q12h) for one week before cecal ligation and puncture (CLP)...

BACKGROUND: The development and introduction of combined therapy represent a challenge for analysis due to severe overlapping of their UV spectra in case of spectroscopy or the requirement of a long tedious and high cost separation technique in case of chromatography. Quality control laboratories have to develop and validate suitable analytical procedures in order to assay such multi component preparations. METHOD: New spectrophotometric methods for the simultaneous determination of simvastatin (SIM) and nicotinic acid (NIA) in binary combinations were developed...

OBJECTIVES: The association of transaortic flow rate (FR) with outcomes was tested in 1,661 patients with aortic valve stenosis (AS) in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. BACKGROUND: Low transaortic flow may complicate grading of AS. However, the association of lower transaortic FR with adverse outcomes has not been reported. METHODS: Transaortic FR was calculated from Doppler-derived stroke volume in milliliters divided by systolic ejection time in seconds and considered low if <200 ml/s...

Some statins, such as atorvastatin, have proven renoprotective effects. The comparative renoprotective potential of simvastatin is less clear. This study aimed to compare the renoprotective effects of simvastatin with atorvastatin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). This observational study examined the medical records of 271 patients who were treated at the Guangdong Cardiovascular Institute from April 2004 to February 2008. Patients had received either 40 mg simvastatin (n = 128) or 20 mg atorvastatin (n = 143), daily, for a period of at least 6 months following PCI...

Lung adenocarcinoma accounts for ∼40% of lung cancers, the leading cause of cancer-related death worldwide, and current therapies provide only limited survival benefit. Approximately half of lung adenocarcinomas harbor mutations in TP53 (p53), making these mutants appealing targets for lung cancer therapy. As mutant p53 remains untargetable, mutant p53-dependent phenotypes represent alternative targeting opportunities, but the prevalence and therapeutic relevance of such effects (gain of function and dominant-negative activity) in lung adenocarcinoma are unclear...

Statins are cholesterol lowering drugs and have shown beneficial effects on glaucoma. With regard to the mechanism of statin action on glaucoma, we investigated the effects of statins on transforming growth factor-beta 2 (TGF-β2)-induced expression of extracellular matrix (ECM) proteins in human astrocytes of the optic nerve head (ONH) lamina cribrosa (LC). By using primary human ONH astrocytes, we found that both simvastatin and lovastatin inhibited TGF-β2-mediated expression of ECM proteins such as connective tissue growth factor, collagen I, fibronectin, and plasminogen activator inhibitor-1...

Objective: To evaluate the efficacy of oral nattokinase (NK) in the reduction of common carotid artery intimal medial thickness (CCA-IMT) and carotid artery plaque size and in lowering blood lipids, and to explore the underlying mechanism of actions of NK and its potential clinical use. Methods: All enrolled patients were from the Out-Patient Clinic of the Department of TCM at the 3(rd) Affiliated Hospital of Sun Yat-sen University. Using randomised picking method, all patients were randomly assigned to one of two groups, NK and Statin (ST) group...

Glycosaminoglycans (GAGs) play an important role in lipoprotein metabolism. In liver, it facilitates the uptake of remnants through receptor-independent endocytosis. However, changes in liver GAGs during diet-induced hypercholesterolemia with normal levels of fat feeding are unknown. Present paper highlights the effect of diet-induced hypercholesterolemia with normal levels (5%) of fat on liver GAGs and other associated lipoprotein receptors. Hypercholesterolemia was induced in rats by feeding diet supplemented with 0...

Objective To identify potential genes that may be involved in lipid metabolism in rats after treatment with aqueous extract of Arctium lappa L (burdock). Methods Rats were randomly divided into six groups: (i) control (standard diet); (ii) model group (high-fat diet only); (iii) high-fat diet and low-dose aqueous burdock root extract (2 g/kg); (iv) high-fat diet and moderate-dose aqueous burdock root extract (4 g/kg); (v) high-fat diet and high-dose aqueous burdock root extract (8 g/kg); and (vi) a positive control group exposed to a high-fat diet and simvastatin (10 mg/kg)...

This corrects the article DOI: 10.1038/srep13524.

Neuroinflammation is a prominent component of several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease, Parkinson's disease, tauopathies, amyotrophic lateral sclerosis and prion diseases. In such conditions, the ability to decrease neuroinflammation by drug therapy may influence disease progression. Statins have been used to treat hyperlipidemia as well as reduce neuroinflammation and oxidative stress in various tissues. In previous studies, treatment of scrapie-infected mice with the type 1 statins, simvastatin or pravastatin, showed a small beneficial effect on survival time...

OBJECTIVE: To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melegueta (A. melengueta) and Dennettia tripetala (D. tripetala) on CYP 3A enzymes. METHODS: In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay (EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental analysis as implemented in WinNonlin pharmacokinetic program...