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Molecular mechanisms underlying the cholesterollowering effect of Ginkgo biloba extract in hepatocytes: a comparative study with Iovastatin
Aim: To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE). Methods. Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or Iovastatin. Results: GBE decreased the tota...
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Published in: | Acta pharmacologica Sinica 2009 (9), p.1262-1275 |
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Main Author: | |
Format: | Article |
Language: | English |
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Online Access: | Get full text |
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Summary: | Aim: To explore the molecular mechanisms underlying the cholesterol-lowering effect of a Ginkgo biloba extract (GBE). Methods. Enzyme activity, cholesterol flux and changes in gene expression levels were assessed in cultured hepatocytes treated with GBE or Iovastatin. Results: GBE decreased the total cholesterol content in cultured hepatocytes and inhibited the activity of HMG-CoA reductase, as determined by an in vitro enzyme activity assay. In addition, GBE decreased cholesterol influx, whereas Iovastatin increased cholesterol influx. GBE treatment induced significant increases in the expression of cholesterogenic genes and genes involved in cholestero metabolism, such as SREBF2, as determined by cDNA microarray and real-time RT-PCR. Furthermore, INSIG2, LDLR, LRP1, and LRPIO were differentially regulated by GBE and Iovastatin. The data imply that the two compounds modulate cholesterol metabolism through distinct mechanisms. Conclusion: By using a gene expression profiling approach, we were able to broaden the understanding of the molecular mechanisms by which GBE lowers cellular cholesterol levels. Specifically, we demonstrated that GBE exhibited dual effects on the cellular cholesterol pool by modulating both HMG-CoA reductase activity and inhibiting cholesterol influx. |
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ISSN: | 1671-4083 1745-7254 |