AIM: The current study was undertaken to assess anti-hyperlipidemic activity of Pistacia lentiscus fatty oil (PLFO) in rabbits following a hyperlipidemic diet. METHOD: Twenty healthy female (WNZ) rabbits were divided into four groups of five animals each: (a) normal control (NC group) receiving standard diet, (b) hyperlipidemic control (EY) group receiving standard diet and gavaged daily with egg yolk (10 mL), (c) hyperlipidemic + PLFO (EY + PLFO) group receiving as the EY group and treated daily with PLFO (2 mL/kg BW, (d) hyperlipidemic + simvastatin (EY + SVS) group receiving as the EY group and treated once daily with 2.5 mg/kg BW of simvastatin. At the end of the six-week experimental period, the lipidemic profiles of the different groups were investigated. RESULTS: In the EY group, the egg yolk resulted in a significant increase of total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, and the LDL-C/HDL-C ratio. Both the EY + PLFO and EY + SVS groups, when compared to the EY group, showed a significant decrease of TC, TG, LDL-C, and the LDL-C/HDL-C ratio. However, with respect to HDL-C the differences were not significant. The TGs were significantly lower (P < 0.001) in the simvastatin-treated group when compared to rabbits treated in the PLFO group. CONCLUSION The study concludes that P. lentiscus fatty oil (PLFO) possesses anti-hyperlipidemic properties at least in reducing total cholesterol, LDL-cholesterol and triglycerides.
Animals ; Anticholesteremic Agents ; pharmacology ; therapeutic use ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Diet ; Egg Yolk ; Female ; Fruit ; Hyperlipidemias ; blood ; drug therapy ; etiology ; Lipids ; blood ; Phytotherapy ; Pistacia ; Plant Oils ; pharmacology ; therapeutic use ; Rabbits ; Simvastatin ; pharmacology ; therapeutic use ; Triglycerides ; blood

To observe the effects of simvastatin on plasma superoxide dismutase (SOD), malonaldehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α) as well as uric acid (UA) and serum lipids in patients with stable angina. METHODS Eighty-five patients with stable angina were divided into 4 groups, including hyperlipemia treatment group (HLT), hyperlipemia control group (HLC), normolipemia treatment group (NLT), and normolipemia control group (NLC). All the patients received routine treatment according to the guideline of CHD treatment, and those in the treatment groups were given Simvastatin (40 mg) every night, whereas those in the control group received placebo for 3 months. Before and after the treatments, the levels of plasma 8-iso-PGF2α were measured by enzyme-linked immunosorbent assay, and the plasma levels of SOD and MDA were detected by colorimetric method. LDL, HDL, TC, TG, and UA were also measured biochemically. RESULTS Compared with the control group, both of the treatment groups showed significantly increased levels of SOD and decreased MDA, 8-iso-PGF2α, UA and plasma lipids after the treatments (P<0.05). CONCLUSION In patients with coronary heart disease, simvastatins can decrease plasma lipids, inhibit lipid peroxidations, and promote the clearance of free radicals, thereby alleviating the oxidative stress.
Aged ; Angina Pectoris ; blood ; drug therapy ; Dinoprost ; analogs & derivatives ; blood ; Female ; Humans ; Male ; Malondialdehyde ; blood ; Middle Aged ; Simvastatin ; pharmacology ; therapeutic use ; Superoxide Dismutase ; blood

AIMTo evaluate the inhibitory effect of simvastatin via investigating the overall expression level of proteins in the artery of atherosclerotic rabbit.

METHODSExperimental model was established by feeding the rabbits a high fat diet (cholesterol 0.5 g.kg-1.d-1, lard 0.5 mL.kg-1.d-1) for 8 weeks. Then simvastatin (5 mg.kg-1) were fed for 4 weeks to the rabbits. The overall protein levels were measured using two-dimensional gel electrophoresis and a PDQUEST data processing.

RESULTSTwenty nine protein spots showed significant quantitative changes in comparison with the normal and the diseased rabbits. Furthermore, after the diseased rabbit having taken simvastatin, an obvious decay of symptom of fatty liver was observed, and the intensity of most spots has not been back-regulated.

CONCLUSIONSimvastatin facilitates the metabolism of fat in the blood, but the lesion of the internal wall of the atherosclerotic artery cannot be restored.

Animals ; Arteries ; drug effects ; pathology ; Arteriosclerosis ; drug therapy ; metabolism ; pathology ; Diet, Atherogenic ; Fatty Liver ; pathology ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Male ; Proteins ; metabolism ; Rabbits ; Random Allocation ; Simvastatin ; pharmacology ; therapeutic use

The present study examined the functional profile of dendritic cells (DCs) in patients with rheumatoid arthritis (RA) and the effects of simvastatin on the function of DCs. A total of 40 patients who was recently diagnosed as having RA were equally assigned to two groups: the routine treatment group (group R) and the routine treatment plus simvastatin group (group R+S). Twenty healthy individuals served as control. The peripheral blood mononuclear cells (PBMCs) were isolated before and 4 weeks after the treatment and then cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM-CSF) to prepare mature DCs. The expression of co-stimulating factor CD86 on the surface of DCs was assessed by flow cytometry. And the stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR). The contents of cytokines in culture supernatants of DCs in MLR were detected by ELISA. Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were detected. The relationship between the expression of CD86 and the blood CRP level was also investigated. The results showed that, as compared with the control group, the CD86 expression and the level of cytokines secreted by DCs were significantly increased in RA patients and greater stimulating capacity of DCs in MLR was demonstrated in RA patients. T lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2, IL-17, TNF-α and INF-γ) and lower level of anti-inflammation cytokine (IL-10). The function of DCs was markedly weakened and the level of hs-CRP and low-density lipoprotein was substantially lowered in group R+S in comparison to group R. The CD86 expression was positively correlated with hs-CRP. It was concluded that DCs in RA are highly activated and DC-initiated immune reaction may play an important role in the pathogenesis of RA. Simvastatin administration can significantly inhibit the DCs function and reduce the level of hs-CRP, indicating the suppression on inflammatory reaction may be one of the mechanisms by which simvastatin exerts its effect in treating RA.
Adult ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; immunology ; C-Reactive Protein ; metabolism ; Cytokines ; metabolism ; Dendritic Cells ; drug effects ; immunology ; Female ; Humans ; Male ; Middle Aged ; Simvastatin ; pharmacology ; therapeutic use

To investigate the anti-cardiac hypertrophic mechanism of statins, thirty-eight male Wistar rats were randomly allocated to four groups. Rats in model group received nitric oxide synthase inhibitor, N-nitro-L-arginine (L-NNA) 15 mg/(kg.d) by peritoneal injection. Rats in simvastatin treatment groups were given simultaneously L-NNA as those in model group and simvastatin 5 or 30 mg/(kg.d) intragastrically respectively. Rats in control group received the same volume of normal sodium. Left ventricular function, left ventricular mass index (LVMI), the content of brain natriuretic peptide (BNP) in plasma and myocardium, myocardial hydroxyproline and heme oxygenase activity were determined after 6 weeks. The results showed that rats in model group developed significant cardiac hypertrophy associated with reduced left ventricular function compared with the control group. However, compared with the model group, L-NNA-induced cardiac hypertrophy of rats was significantly relieved in simvastatin treatment groups, associated with improved left ventricular function, decreased LVMI, lower BNP levels in plasma and myocardium, lower content of myocardial hydroxyproline, and increased myocardial heme oxygenase (HO) activity. In cultured rat neonatal cardiomyocytes, simvastatin (30 or 100 mumol/L) significantly increased heme oxygenase-1 (HO-1) mRNA expression, HO activity as well as the production of CO in cardiomyocytes. Cultured with zinc protoporphyrin, a HO inhibitor, or simvastatin alone did not change [(3)H]leucine uptake of cardiomyocytes. However, cocultured with simvastatin significantly inhibited the cardiomyocyte [(3)H]leucine uptake induced by angiotensin II in a concentration-dependent manner. Cotreatment with zinc protoporphyrin significantly abolished the suppressive effect of simvastatin on cardiomyocyte [(3)H]leucine uptake. These data suggest that the activation of HO-1/CO pathway may be one of the important mechanisms by which statins inhibit cardiac hypertrophy caused by hypertension.
Angiotensins ; antagonists & inhibitors ; pharmacology ; Animals ; Carbon Monoxide ; metabolism ; Cardiomegaly ; etiology ; prevention & control ; Cell Enlargement ; drug effects ; Heme Oxygenase-1 ; metabolism ; Hypertension ; complications ; drug therapy ; Male ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Simvastatin ; pharmacology ; therapeutic use

OBJECTIVETo observe the effect of Buyang Huanwu Decoction (BYHWD), a representative formula of qi benefiting blood activating method on aorta Rho associated coiled-coil forming protein serine/threonine kinase (Rhokinase, ROCK) and nuclear transcription factor kappa B (NF-κB) p65 mRNA expressions and levels of blood lipids in atherosclerosis (AS) model rats.

METHODSThe AS rat model was prepared by vitamin D3 and high fat diet. Totally 60 rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the low dose BYHWD group (10 g/kg), the high dose BYHWD group (20 g/kg), the Simvastatin control group (0.6 mg/kg), and the BYHWD prevention group (10 g/kg), 10 in each group. After successful modeling all medication was intervened for 28 days. Expression levels oxidized low density lipoprotein (ox-LDL) were detected by ELISA. Levels of TG, TC, LDL-C, HDL-C were determined by enzyme method. Pathological changes of aortic tissue were observed under light microscope. mRNA expressions of Rho kinase and NF-κB p65 in aorta were detected by real time (RT) PCR.

RESULTSHigh fat diet and peritoneal injection of vitamin D3 could induce AS rat model. Typical atheromatous plaque formed in aorta of AS model rats. Compared with the normal control group, levels of TC, TG, LDL-C, and ox-LDL significantly increased in the model group, but the HDL-C level decreased (P < 0.01). Compared with the model group, levels of TC, TG, LDL-C, and ox-LDL all decreased, but HDL-C increased in low and high dose BYHWD groups, the Simvastatin control group, and the BYHWD prevention group (P < 0.05, P < 0.01). Compared with the low dose BYHWD group, above-mentioned indices were more obviously lowered in the high dose BYHWD group, the Simvastatin control group, and the BYHWD prevention group (P < 0.05). Compared with the normal control group, mRNA expression levels of Rho kinase and NF-κB p65 significantly increased in the model group (P < 0.01). Compared with the model group, mRNA expressions of Rho kinase and NF-κB p65 obviously decreased in low and high dose BYHWD groups, the Simvastatin control group, and the BYHWD prevention group (P < 0.01). Compared with the low dose BYHWD group, the two indicators were more obviously lowered in the high dose BYHWD group, the Simvastatin control group, and the BYHWD prevention group (P < 0.05). But there was no statistical difference in blood lipids levels, mRNA expression levels of Rho kinase or NF-κB p65 among the high dose BYHWD group, the Simvastatin control group, and the BYHWD prevention group (P >0. 05).

CONCLUSIONSBYHWD could down-regulate mRNA expression levels of Rho kinase and NF-κB p65, lower levels of blood lipids, and fight against AS. Suppressing Rho kinase pathway might be one of its mechanisms.

Animals ; Aorta ; Atherosclerosis ; genetics ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Gene Expression ; drug effects ; Lipids ; Lipoproteins, LDL ; NF-kappa B ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Simvastatin ; Transcription Factor RelA ; metabolism ; rho-Associated Kinases ; metabolism

OBJECTIVETo investigate the effects of low-dose simvastatin on the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in the renal tubulointerstitium of rats with diabetic nephropathy.

METHODSSixty male SD rats were randomly divided into three groups: Group C (control group), Group D, in which diabetes was induced by stroptozotocin (STZ) and Group DS, in which STZ-induced diabetic rats were treated with low-dose (no cholesterol-lowering effect) simvastatin. The following parameters were measured after 6 weeks and 12 weeks in each groups, respectively: body weight and kidney weight, 24-h urinary albumin excretion (UAE), biochemical indexes including blood glucose (GLU), low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG) and serum creatinine (SCr). The expression of CTGF and α-SMA in renal tubulointerstitium was assessed by immunohistochemical method.

RESULTAfter 6 and 12 weeks, there were no significant differences in SCr, LDL, HDL and TG levels among all three groups. The expression levels of CTGF and α-SMA in the tubulointerstitium of Group DS were significantly decreased compared with those of Group D at week 6 (P<0.05); there were no significant differences compared with Group C (P>0.05). After 12 weeks, CTGF and α-SMA expressions in Group DS were also lower than those in Group D (P<0.05); while higher than those in Group C (P<0.05).

CONCLUSIONSimvastatin with a under cholesterol-lowering dose, can decrease the expression levels of CTGF and α-SMA in renal tubulointerstitium of rats with diabetic nephropathy, by which the progression of the tubulointerstitial fibrosis would be delayed.

Actins ; metabolism ; Animals ; Connective Tissue Growth Factor ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Kidney ; drug effects ; metabolism ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology ; therapeutic use

OBJECTIVETo investigate the underlying molecular mechanism of the cholesterol-blocking drug, simvastatin, in treating nonalcoholic fatty liver fibrosis.

METHODA rat model of nonalcoholic fatty liver fibrosis was established by feeding Wistar rats a fat-rich diet. After treatment with simvastatin (4 mg/kg/day), liver histological specimens were stained with hematoxylin-eosin and Masson's trichrome for microscopic analysis. Expression of adenosine monophosphate-activated protein kinase-alpha (AMPKa) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR; for mRNA) and Western blotting (protein). The levels of serum total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-alpha (TNFa) were measured by standard biochemical assays. The human hepatic stellate cell line, LX-2 (quiescent or activated), was treated with transforming growth factor-beta 1 (TGF-b1) alone, simvastatin alone, or TGF-b1 + simvastatin. RT-PCR and Western blotting were used to determine changes in AMPKa mRNA and protein expression, respectively.

RESULTSIn the rat model of nonalcoholic fatty liver fibrosis, the extent of pathological changes in hepatic tissues correlated with severity of disease progression. The levels of serum TC, TG, ALT, AST and TNFa were increased significantly in model rats (vs. healthy controls; all, P less than 0.01). AMPKa mRNA expression and activity was significantly decreased in model rats (vs. healthy controls; P less than 0.01 and P less than 0.05, respectively). Simvastatin, treatment significantly improved all of these parameters in model rats (vs. untreated model rats; all, P less than 0.05). In vitro simvastatin treatment of human HSCs significantly increased AMPKa activity (quiescent LX-2: 0.93+/-0.10 vs. 0.72+/-0.09, activated LX-2: 0.72+/-0.10 vs. 0.54+/-0.10, q=7.00, 6.00; all, P less than 0.01), decreased a-smooth muscle actin expression (mRNA: 0.30+/-0.02 vs. 0.36+/-0.02, protein: 0.30+/-0.03 vs. 0.38+/-0.02, q=11.245, 11.216; all, P less than 0.01), and decreased collagen I expression (mRNA: 0.30+/-0.03 vs. 0.37+/-0.03, protein: 0.25+/-0.03 vs. 0.33+/-0.03, q=8.791, 11.163; all, P less than 0.01).

CONCLUSIONSimvastatin may improve nonalcoholic fatty liver fibrosis by inducing AMPK phosphorylation.

Adenylate Kinase ; metabolism ; Animals ; Cell Line ; Fatty Liver ; drug therapy ; metabolism ; pathology ; Hepatic Stellate Cells ; drug effects ; enzymology ; Humans ; Liver Cirrhosis ; metabolism ; pathology ; Male ; Rats ; Rats, Wistar ; Simvastatin ; pharmacology ; therapeutic use

OBJECTIVETo investigate the effect of apolipoprotein B (apoB) and E (apoE) genetic variations on lipid profile at baseline (before treatment), and also on the subsequent response to simvastatin therapy.

METHODSEighty-eight patients with hyperlipidemia were treated with simvastatin 5mg daily. The plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apo B were measured pre-treatment and at the end of the 4th, 8th and 12th post-treatment week. Polymorphisms of apoB at XbaI locus and apoE were determined by restriction fragment length polymorphism (RFLP).

RESULTSIn all patients, relative frequencies of X- allele and X+ allele were 0.943 and 0.057 for apoB gene respectively. For apoE gene the relative frequency of epsilon2 allele was determined as 0.182, epsilon3 as 0.580 and epsilon4 as 0.238. The reduction in TC level was more prominent in patients carrying X- allele than in those with X+ allele following treatment (-23. 9% vs. -13. 6%, P < 0. 05). Compared with patients carrying epsilon3 or epsilon4 allele, those with epsilon2 allele showed a significantly higher percentage in reduction of apoB level after treatment (P < 0.05).

CONCLUSIONThe relative frequency of apoB X+ allele is high in patients with hyperlipidemia, in whom the TC-lowering efficacy is decreased following treatment of simvastatin. The relative frequencies of epsilon2 and epsilon4 are also high in hyperlipidemic patients, and the epsilon2 allele is associated with reduction in apoB level during lipid-relating therapy.

Aged ; Alleles ; Apolipoproteins B ; genetics ; Apolipoproteins E ; genetics ; Cholesterol ; blood ; Cholesterol, LDL ; blood ; Female ; Gene Frequency ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length ; Simvastatin ; pharmacology ; therapeutic use ; Triglycerides ; blood

OBJECTIVETo investigate the role and mechanism of Astragalus (AS) and saponins of Panax notoginseng (PNS) in treating type 2 diabetic macroangiopathy.

METHOD94 patients with type 2 diabetic macroangiopathy were divided into two groups randomly: group treated with Simvastatin and group treated with AS and PNS, compared with 40 healthy control subjects. Serum level of MMP-9 and lipid in patients and healthy subjects were measured before and after treatment.

RESULTThe serum levels of MMP-9, TG, TC, LDL-C, VLDL-C in patients with type 2 diabetic macroangiopathy were improved, while the levels of HDL-C were decreased. Like Simvastatin AS and PNS had the function of reducing MMP-9 and accommodating lipid metabolism.

CONCLUSIONBesides accommodating lipid metabolism, AS and PNS can also reduce the level of serum MMP-9 soas to treat type 2 diabetic macroangiopathy.

Aged ; Astragalus membranaceus ; chemistry ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; enzymology ; Diabetic Angiopathies ; blood ; drug therapy ; enzymology ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Female ; Ginsenosides ; isolation & purification ; therapeutic use ; Humans ; Hypolipidemic Agents ; therapeutic use ; Lipids ; blood ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Panax ; chemistry ; Phytotherapy ; Plants, Medicinal ; chemistry ; Simvastatin ; therapeutic use