There exists many kinds and a huge number of terpenoid in medicinal plants, which show a wide range of pharmacological activities. 3-Hydroxy-3-metllylglutaryl coenzyme A reductase(HMGR) is a key rate-limiting enzyme in terpenoid biosynthetic pathway . HMGR plays an important role in the regulation of secondary metabolism of the terpenoid. The paper summarized the biological function and the catalytic mechanism of HMGR, the cloning and the structure of the gene as well as its research progress in some medicinal plants.
Hydroxymethylglutaryl CoA Reductases ; metabolism ; Plants, Medicinal ; enzymology ; Terpenes ; metabolism

OBJECTIVETo study the hypolipidemic active compounds from Crataegus pinnatifida and mechanism of action of those.

METHODGuided by the inhibitory activity to HMG-CoA reductase, the active compounds were separated and purified with macroporous resin and silica gel.

RESULTFour active compounds were obtained, which were quercetin, hyperoside, rutin and chlorogenic acid, the sum of their inhibitory rate was 50.01%, and the total inhibitory rate of the mixture of four active compounds matched was 79.48%.

CONCLUSIONQuercetin and hyperoside were the principle active components inhibiting HMG-CoA reductase in Hawthorn fruit, and there were synergistic action among them.

Crataegus ; chemistry ; Fruit ; chemistry ; Hydroxymethylglutaryl CoA Reductases ; analysis ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Plant Extracts ; pharmacology

A 42-year-old woman presented with ichthyosiform eruptions on her trunk and buttock which developed 20 days prior to consulatation. She had taken the cholesterol-lowering drug(lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor) for 4 months. After stopping the drug, the skin lesions gradually improved and after two months most of the lesions had disappeared. After 3 months of follow up the skin lesions could not be seen any more. Acquired ichthyosis in our patient could be an untoward effect of HMG CoA reductase inhibitor by disturbing the skin lipid metabolism.
Adult ; Buttocks ; Female ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl CoA Reductases ; Ichthyosis* ; Lipid Metabolism ; Lovastatin ; Oxidoreductases ; Skin

BACKGROUND: The combination therapy of HMG CoA reductase inhibitor (statin) and fibrate is more effective than each ones in managing combined dyslipidemia. However, this therapy tends to be avoided due to potential risk of rhabdomyolysis. The aim of the study was to reevaluate the efficacy and safety of combination therapy. METHODS: A total 61 patients were divided into three groups according to lipid levels and medications; statin+fibrate group (n=10), statin group (n=31) and fibrate group (n=18). Patients with active hepatitis or renal dysfunction who were at high risk for complications were excluded. Lipid profiles were measured before and 2 months after medications. RESULTS: Combination therapy markedly decreased total cholesterol, low density lipoproteincholesterol (LDL-C) and triglyceride concentrations (p=0.008, p=0.028 and p=0.018 respectively), and increased high density lipoprotein-cholesterol (HDL-C)(p=0.028). The effects of this therapy on HDL-C and triglyceride were more potent than those of statin. Combination therapy was more effective in lowering LDL-C than fibrate. Serious complications such as myopathy and marked elevation of transaminase level were not observed in all groups. In statin+fibrate group, transaminase level was elevated slightly above the normal range in two cases. Creatine kinase level showed the trend to increase with borderline significance. However the levels were within normal range in 9 cases and elevated twofold in one patient. CONCLUSION: Combination therapy of statin and fibrate was effective in combined dyslipidemia and well tolerated in patients without high risk for the complications although the number of cases was small to get a conclusion.
Cholesterol ; Creatine Kinase ; Dyslipidemias* ; Hepatitis ; Humans ; Hydroxymethylglutaryl CoA Reductases* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypolipidemic Agents ; Lipoproteins ; Muscular Diseases ; Reference Values ; Rhabdomyolysis ; Triglycerides

BACKGROUND: High levels of C-reactive protein (CRP) are associated with an increased risk for cardiovascular diseases. Most reports on the effect of fibrate on CRP level have inadequate study designs and the results are inconsistent. This study was designed to evaluate the effect of fenofibrate on CRP levels in hypertriglyceridemic patients. METHODS: Patients with triglyceride (TG) level over 200 mg/dL were treated with 200 mg of fenofibrate (Fenofibrate group, n=30) or with general measures (Control group, n=30). Patients with CRP levels >10 mg/L were excluded. Patients with hypercholesterolemia were treated with HMG CoA reductase inhibitor (Statin group, n=30). Lipid and lipoprotein levels were measured before and 2 months after medication. RESULTS: Baseline characteristics were similar in Fenofibrate and Control groups. Baseline CRP levels were independently associated with the presence of diabetes mellitus. Fenofibrate therapy did not change CRP levels (1.67+/-1.60 vs 1.76+/-1.88 mg/L, p=0.79) as did Control group (p=0.46). When both Fenofibrate and Control groups were divided into three subgroups in terms of baseline CRP levels, CRP levels were increased in the lowest group (p=0.019), did not change in the middle and the highest groups (p=0.89 and p=0.47 respectively). In patients with baseline CRP level > or =3 mg/L, CRP levels were decreased (p=0.041). Changes of CRP levels were independently associated with baseline CRP levels. Statin therapy decreased CRP levels (p=0.046). CONCLUSIONS: Fenofibrate did not change CRP levels in hypertriglyceridemic patients. Cardioprotective effects of fibrates may not be associated with anti-inflammatory mechanisms in contrast to those of statins.
C-Reactive Protein* ; Cardiovascular Diseases ; Diabetes Mellitus ; Fenofibrate* ; Fibric Acids ; Humans ; Hydroxymethylglutaryl CoA Reductases ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Lipoproteins ; Triglycerides

β-carotene has a wide range of application in food, pharmaceutical and cosmetic industries. For microbial production of β-carotene in Saccharomyces cerevisiae, the supply of geranylgeranyl diphosphate (GGPP) was firstly increased in S. cerevisiae BY4742 to obtain strain BY4742-T2 through over-expressing truncated 3-hydroxy-3-methylglutaryl-CoA reductase (tHMGR), which is the major rate-limiting enzyme in the mevalonate (MVA) pathway, and GGPP synthase (GGPS), which is a key enzyme in the diterpenoid synthetic pathway. The β-carotene synthetic genes of Pantoea agglomerans and Xanthophyllomyces dendrorhous were further integrated into strain BY4742-T2 for comparing β-carotene production. Over-expression of tHMGR and GGPS genes led to 26.0-fold increase of β-carotene production. In addition, genes from X. dendrorhous was more efficient than those from P. agglomerans for β-carotene production in S. cerevisiae. Strain BW02 was obtained which produced 1.56 mg/g (dry cell weight) β-carotene, which could be used further for constructing cell factories for β-carotene production.
Basidiomycota ; enzymology ; Farnesyltranstransferase ; genetics ; metabolism ; Hydroxymethylglutaryl CoA Reductases ; genetics ; metabolism ; Metabolic Engineering ; Polyisoprenyl Phosphates ; Saccharomyces cerevisiae ; metabolism ; beta Carotene ; biosynthesis

Replication of hepatitis C virus (HCV) is regulated by statin, one of 3-hydroxy-3-methylglutaryl CoA reducatase (HMG CoA reductase) inhibitors that block mevalonate pathway and cholesterol biosyntheis, which has been used usefully for health improvement and disease control in clinic. In order to know which statin can be used to inhibit HCV replication, we examined the effects of HCV genotype 1b replication by 6 kinds of statins with different structure. We treated six statins to HCV genotype 1b replicon cell. Atorvastatin, simvastatin, fluvastatin, mevastatin, and lovastatin inhibited HCV RNA replication and HCV protein expression in HCV genotype 1b replicon cells, though pravastatin did not affect HCV replication. In order to know whether inhibition of HCV replication by statin is depended on HCV genotype, we treated the statins to HCV genotype 2a producing cells, and investigated HCV RNA replication and HCV protein expression. HCV RNA replication and protein expression was not affected in HCV genotype 2a producing cells by treatment of statins and cholesterol inhibitor. These results suggest that HMG-CoA reductase and cholesterol inhibitors might be used depending on HCV genotype. In addition, inhibition of HCV genotype 1b replication by statins has been depended on structure of various statins which should be seriously selected for HCV clinic. In future, we will study on inhibition of another HCV genotype replication by HMG-CoA reductase and cholesterol inhibitors.
Acyl Coenzyme A ; Anticholesteremic Agents ; Atorvastatin Calcium ; Cholesterol ; Fatty Acids, Monounsaturated ; Genotype ; Hepacivirus ; Heptanoic Acids ; Hydroxymethylglutaryl CoA Reductases ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Indoles ; Lovastatin ; Mevalonic Acid ; Oxidoreductases ; Pravastatin ; Pyrroles ; Replicon ; RNA ; Simvastatin

The present study was designed to isolate and characterize a purified extract from Fusarium solani FG319, termed MFS (Metabolite of Fusarium solani FG319) that showed anti-atherosclerosis activity by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Response surface methodology (RSM) was employed to achieve an improved yield from the fermentation medium. The inhibiting effect of the isolate, MFS, on HMG-CoA reductase was greater than that of the positive control, lovastatin. The average recovery of MFS and the relative standard deviation (RSD) ranged between 99.75% to 101.18%, and 0.31% to 0.74%, respectively. The RSDs intra- and inter-assay of the three samples ranged from 0.288% to 2.438%, and from 0.934% to 2.383%, respectively. From the RSM, the concentration of inducer, cultivation time, and culture temperatures had significant effects on the MFS production, with the effect of inducer concentration being more pronounced that other factors. In conclusion, the optimal conditions for the MFS production were achieved using RSM and that MFS could be explored as an anti-atherosclerosis agent based on its ability to inhibit HMG-CoA reductase.
Analysis of Variance ; Biological Factors ; isolation & purification ; pharmacology ; Chromatography, High Pressure Liquid ; Fermentation ; physiology ; Fusarium ; metabolism ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; isolation & purification ; pharmacology ; Lovastatin ; pharmacology ; Nucleic Acid Amplification Techniques

This study was purposed to investigate the effect of onion or beet on plasma and liver lipids, erythrocyte Na efflux channels and platelet aggregation in simvastatin (SIM) treated hypercholesterolemic rats. Forty Sprague Dawley rats were divided into four groups and fed 0.5% cholesterol based diets containing 2 mg/kg BW simvastatin or simvastatin with 5% onion or beet powder. Plasma total cholesterol was significantly increased in SIM group compared with the control (p<0.01), and the elevated plasma total cholesterol of SIM group was significantly decreased in SIM-onion and SIM-beet groups (p<0.05). HDL-cholesterol in SIM-beet group was significantly increased compared with other groups (p<0.05). Platelet aggregation in both the maximum and initial slope was significantly decreased in SIM group compared with SIM-onion group (p<0.05). Na-K ATPase was significantly decreased in SIM group compared with the control, SIM-onion and SIM-beet groups (p<0.05). Na passive leak was significantly increased in all groups treated with SIM compared with the control (p<0.05). The total Na efflux was decreased in SIM group and increased in SIM-onion group and the difference between these two groups was significant (p<0.05). There was no difference in intracellular Na among groups. In present study, simvastatin, a HMG CoA reductase inhibitor at dose of 2mg/kg BW/day rather increased plasma total cholesterol in rats, inferring that the action mechanism of simvastatin on cholesterol metabolism differ between rat and human. Onion and beet play favorable roles in cardiovascular system by restoring the reduced Na efflux through Na-K ATPase and Na-K cotransport in SIM treated rats.
Adenosine Triphosphatases ; Animals ; Beta vulgaris ; Blood Platelets ; Cardiovascular System ; Cholesterol ; Diet ; Erythrocytes ; Humans ; Hydroxymethylglutaryl CoA Reductases ; Liver ; Onions ; Plasma ; Platelet Aggregation ; Rats ; Rats, Sprague-Dawley ; Simvastatin

OBJECTIVES: Apolipoprotein E genetic polymorphism was screened in subjects with FH to determine the genetic effects of Apo E polymorphism on basal cholesterol levels, severity of coronary atherosclerosis and response to lipid lowering therapy using HMG CoA reductase inhibitor. METHODS: Total 45 unrelated patients with FH (M:F= 24:21, 48.0/11.5yr.) were included in this study. Apolipoprotein E genetic polymorphism was screened. Clinical parameters were checked. Change of lipid profile to lovastatin,; 20mg/d (n=19), 40mg/d (n=12), and of Achilles tendon thickness were analysed. RESULTS: 1) Genotype frequencies of E2/3, 3/3, 4/3 were 8.9, 60.0, 31.1% respectively, and allele frequencies of epsilon2, epsilon3, and epsilon4 were 0.044, 0.800, and 0.155 respectively.2) Presence and degree of coronary atherosclerosis, the thickness of Achilles tendon and lipid levels were not significantly different by apolipoprotein E genotype.3) On multivariate study, age, triglyceride and cholesterol /high density lipoprotein were significantly related to presence of coroanry atherosclerosis. 4) Percent reduction of LDL-cholesterol by lovastatin was significantly low in subjects having E4/3 genotype than those having E3/3 genotype (p=0.05; 40mg/d), and the percent reduction of Achilles tendon thickness was significantly low in subjects having E4/3 genotype than those having E3/3 genotype (p=0.037; 20mg/d). CONCLUSION: The distribution of apolipoprotein E genotype in patients with familial hypercholesterolemia was not significantly different with that in normal subjects. But apolipoprotein E polymorphism may affect the reduction of LDL-cholesterol and Achilles tendon xanthoma with medication of HMG CoA reductase inhibitor in patients with familial hypercholesterolemia.
Achilles Tendon ; Apolipoproteins E ; Apolipoproteins* ; Atherosclerosis ; Cholesterol ; Coronary Artery Disease* ; Coronary Vessels* ; Gene Frequency ; Genotype ; Humans ; Hydroxymethylglutaryl CoA Reductases ; Hyperlipoproteinemia Type II* ; Lipoproteins ; Lovastatin ; Polymorphism, Genetic* ; Triglycerides ; Xanthomatosis