Linked Life Data

18712086

Source:http://linkedlifedata.com/resource/pubmed/id/18712086

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pubmed-article:18712086pubmed:abstractTextA molecular complex of simvastatin (SV) and glycyrrhyzic acid (GA) (at the ratio of 1 : 4), has been synthesized. The complex named "simvaglyzin" (SVG) was stable in aqeous and aqua-alcohol solutions at GA concentrations exceeding 0.2 mM. In vitro SVG acted as uncompetitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase (Ki = 94 nM). Appearance of this inhibitory activity is associated with the cytochrome P450-dependent conversion of SVG. The addition of 1 mM methyrapone into incubation medium fully prevented the inhibition of 3-HMG-CoA reductase. SV and SVG (used at 300 nM concentration) inhibited mevalonate synthesis rate by 39.15+/-8.27% and 38.85+/-3.04%, respectively. In vivo SVG showed dose-dependent cholesterol-lowering effect. In rats the cholesterol-lowering effect of SVG used at daily doses corresponding to 66 and 100 mg/kg of SV was equal to the effect of the daily dose 200 mg/kg of SV. The decreases of total cholesterol level in blood serum were 7%, 9% and 8%, respectively. Myotoxicity of those SVG doses estimated by creatine phosphokinase (CPK) activity in blood serum was lower than that of SV. In rats treated with SV the activity of CPK increased by 79% (p<0.01), while in SVG treated rats by 30% and 36% (p<0.05). Any increase of hepatotoxicity markers alanine aminotransferse or aspartate aminotransferase in blood serum was not observed. The data suggest pharmacological synergism attributed to the SV-GA complex formation and elevated safety of the resultant complex compared with the parent compound.lld:pubmed
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pubmed-article:18712086pubmed:articleTitle[Cholesterol lowering properties of a complex compound simvastatin with glycyrrhizic acid (simvaglyzin) in experimental models].lld:pubmed
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