ABSTRACT
The inhibition of 3-hydroxy-3-methylglutaryl CoA reductase [HMGCR] is considered able to decrease serum cholesterol levels and dramatically reduce the risk for cardiovascular and cerebrovascular diseases. The statins, competitive inhibitors of HMGCR, have been employed to control hypercholesterolemia. But their side effects, especially their safety of long-term administration have attracted great attention. Therefore, there is still an urgent requirement for the development of safer inhibitors of HMGCR with less serious side effects. In this study, we cloned and purified the catalytic domain of human HMGCR [delta HMGCR], and applied the method of Ultra Performance Liquid Chromatography [UPLC] to assay delta HMGCR activity and screen its inhibitors from natural products. The results indicated that EGCG can inhibit delta HMGCR in the presence of some glycerol in vitro and can decrease cellular total cholesterol in HepG2 cells. As a consequence, it is promising to put EGCG into the development of hypolipidemic health product
Subject(s)
Hydroxymethylglutaryl CoA Reductases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Glycerol , Chromatography, High Pressure LiquidABSTRACT
<p><b>OBJECTIVE</b>To observe the protective effect of compound acanthopanax senticosus injection (CASI) on myocardial ischemia-reperfusion arrhythmia in rats.</p><p><b>METHOD</b>The myocardial ischemia-reperfusion model was induced by 30 min coronary occulusion and 60 min reperfusion in openchest anesthetized rats. The changes of arrhythmia with electrocardiogram lead II, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), the contents of malondialdehyde (MDA) and Ca2+ in myocardium were determined.</p><p><b>RESULT</b>In rats treated by CASI (in a dosage of 25, 50 and 100 mg x kg(-1) femoral vein infusion at 30 min after coronary occulusion), the incidence of myocardial ischemia-reperfusion ventricular arrhythmias, for instance the ventricular tachycardia (VT) and ventricular fibrillation (Vf), was effectively prevented, the appearing time of arrhythmia was delayed and the duration of arrhythmia was shortened, while the elevated ST segment lowered as well. At the same time, the contents of myocardial Ca2+ and MDA were decreased significantly as well as the activities of myocardial SOD and GSH-Px increased markedly.</p><p><b>CONCLUSION</b>CASI is of protective effect on myocardial ischemia-reperfusion arrhythmia, which may be related to scavenging the oxygen free radicals and Ca2+ overload formed during reperfusion.</p>
Subject(s)
Animals , Anti-Arrhythmia Agents , Pharmacology , Arrhythmias, Cardiac , Drug Therapy , Calcium , Metabolism , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Electrocardiography , Eleutherococcus , Chemistry , Female , Ginsenosides , Pharmacology , Glutathione Peroxidase , Metabolism , Male , Malondialdehyde , Metabolism , Myocardial Reperfusion Injury , Myocardium , Metabolism , Pathology , Panax , Chemistry , Phytotherapy , Plants, Medicinal , Chemistry , Rats , Rats, Wistar , Saponins , Pharmacology , Superoxide Dismutase , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe the protective effect of Acanthopanax senticosus saponins (ASS) on myocardial ischemia-reperfusion injury in rats.</p><p><b>METHOD</b>The myocardial ischemia-reperfusion model was induced by 30 min left anterior descending coronary occlusion and 120 min reperfusion in rats. The changes of myocardial infarct size (MIS), the serum creatine phosphokinase (CK) and lactate dehydrogenase (LDH) activity, the serum lipid peroxidation (LPO) content and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity and plasma endothelin (ET), angiotensin II (Ang II), prostacycline (PGI2) and thromboxane A2 (TXA2) levels and myocardial free fatty acid (FFA) content of infarct and noninfarct area were determined.</p><p><b>RESULT</b>In rats treated by ASS (in a dosage of 25, 50 and 100 mg x kg(-1) i.v. at 30 min after coronary occulusion), the MIS was significantly reduced, the serum CK and LDH activity, the plasma ET, Ang II and TXA2 level and myocardial FFA content declined, while plasma PGI2 level and PGI2/TXA2 was increased signficantly. In addition, serum LPO content declined, SOD and GSH-Px activity were increased markedly.</p><p><b>CONCLUSION</b>ASS has protective effect on myocardial ischemia-reperfusion injury, which may be due to its function of improving free radicals and myocardial metabolism, decreasing plasma ET, Ang II and TXA2 levels and increasing plasma PGI2 level and PGI2/TXA2 ratio etc.</p>
Subject(s)
Animals , Drugs, Chinese Herbal , Pharmacology , Eleutherococcus , Chemistry , Female , Male , Myocardial Reperfusion Injury , Metabolism , Pathology , Myocardium , Metabolism , Pathology , Plant Leaves , Chemistry , Plants, Medicinal , Chemistry , Rats , Rats, Wistar , Saponins , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To observe effects of ginsenoside-Rb (G-Rb) on total cholesterol, lipoprotein cholesterol metabolism and anti-oxidation in experimental hyperlipidemia rats.</p><p><b>METHOD</b>Hyperlipidemia rats were respectively given G-Rb 50, 100, 200 mg x kg(-1) x d(-1) ig for twelve days. Total cholesterol, lipoprotein cholesterol and lipid peroxidation (LPO) contents, prostacycline (PGI2), thromboxane (TXA2), superoxide dismutase (SOD) and blood viscosity were measured. Fat accumulation in liver was also observed.</p><p><b>RESULT</b>Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) in serum, TXA2 in plasma, LPO in serum and liver, and blood viscosity were decreased significantly. High density lipoprotein cholesterol (HDLc) in serum, PGI2 in plasma and SOD in serum and liver were significantly increased by G-Rb (100, 200 mg x kg(-1)) in experimental hyperlipidemia rats. In addition, G-Rb could decrease TC/HDL-c, LDLc/HDL-c ratio, increase PGI2/TXA2 ratio and inhibit fat accumulation in liver.</p><p><b>CONCLUSION</b>G-Rb could have anti-arteriosclerosis effect by improving cholesterol and lipoprotein-cholesterol metabolism, suppressing lipid peroxidation, increasing anti-oxidase activity and PGI2/TXA2 ratio.</p>