title: Molecular mechanisms underlying the cholesterol-lowering effect of Ginkgo biloba extract in hepatocytes: a comparative study with lovastatin.
abstract: OBJECTIVE
  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 lovastatin.
  
  
  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 lovastatin increased cholesterol influx. GBE treatment induced significant increases in the expression of cholesterogenic genes and genes involved in cholesterol metabolism, such as SREBF2, as determined by cDNA microarray and real-time RT-PCR. Furthermore, INSIG2, LDLR, LRP1, and LRP10 were differentially regulated by GBE and lovastatin. The data imply that the two compounds modulate cholesterol metabolism through distinct mechanisms.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Zuo-quan
authors.initials: ZQ
authors.lastname: Xie
authors.forename: Gai
authors.initials: G
authors.lastname: Liang
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Li-bo
authors.initials: LB
authors.lastname: Lin
authors.forename: Sai
authors.initials: S
authors.lastname: Ye
authors.forename: Ji
authors.initials: J
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Guo-ping
authors.initials: GP
authors.lastname: Zhao
authors.forename: Qing-hua
authors.initials: QH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002784:Cholesterol / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D020441:Ginkgo biloba; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects*; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000924:Anticholesteremic Agents; D010936:Plant Extracts; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases
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