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KMID : 0352720050290040159
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Journal of Ginseng Research
2005 Volume.29 No. 4 p.159 ~ p.166
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Ginsenoside Rb2 Upregulates the Low Density Lipoprotein Receptor Gene Expression through the Activation of the Sterol Regulated Element Binding Protein Maturation in HepG2 Cells
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Lim G
Lee HN/Kim EJ/Noh YH/Ro YT/Koo JH
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Abstract
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Ginsenosides, a group of Panax ginseng saponins, exert the lowering effects of plasma cholesterol levels in animals. We had reported earlier that ginsenoside Rb2 upregulate low-density lipoprotein receptor (LDLR) expression via a mechanism that is dependent of the activation of sterol response element binding protein 2 (SREBP-2) expression. This study was conducted to determine the effects of ginsenoside Rb2 on the expression of the hepatic LDLR expression at cellular levels using HepG2 cells, and to evaluate whether the sterol response element binding protein 1 (SREBP-1) was involved in the regulation of LDLR expression. Incubation of HepG2 cells in serum-free medium supplemented with cholesterol (10 μg/ml) for 8 hours decreased the mRNAs of LDLR mRNA by 12% and SREBP-1 mRNA by 35%. Ginsenoside Rb2 antagonized the repressive effects of cholesterol and increased both LDLR and SREBP-1 mRNA expression to 1.5- and 2-fold, respectively. Furthermore, Western blot and confocal microscopic analyses with SREBP-1 polyclonal antibody revealed that ginsenoside Rb2 enhanced the maturation of the SREBP-1 from the inactive precursor form in ER membrane to the active transcription factor form in nucleus. These results suggest that ginsenoside Rb2 upregulates LDLR expression via a mechanism that is dependent of the activation of not only SREBP-2 expression, but also SREBP-1 expression and maturation, and also indicate that the pharmacological value of ginsenoside Rb2 may be distinguished from that of lovastatin which is reported that it upregulate LDLR through SREBP-2 only, not through SREBP-1.
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