title: Evaluation of Ginkgo biloba extract as an activator of human glucocorticoid receptor.
abstract: BACKGROUND
  Ginkgo biloba, which is one of the most frequently used herbal medicines, is commonly used in the management of several conditions, including memory impairment. Previously, it was reported to decrease the expression of peripheral benzodiazepine receptor and the biosynthesis of glucocorticoids, thereby regulating glucocorticoid levels. However, it is not known whether Ginkgo biloba extract regulates the function of the glucocorticoid receptor.
  
  
  OBJECTIVE
  We determined whether Ginkgo biloba extract and several of its chemical constituents affect the activity of human glucocorticoid receptor (hGR).
  
  
  METHODS
  A hGR-dependent reporter gene assay was conducted in HepG2 human hepatocellular carcinoma cells and hGR target gene expression assays were performed in primary cultures of human hepatocytes.
  
  
  RESULTS
  Multiple lots and concentrations of the extract and several of its chemical constituents (ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide) did not increase hGR activity, as assessed by a cell-based luciferase reporter gene assay. The extract did not influence the expression of hGR target genes, including tyrosine aminotransferase (hTAT), constitutive androstane receptor (hCAR), or pregnane X receptor (hPXR), in primary cultures of human hepatocytes. Moreover, hGR antagonism by mifepristone (also known as RU486) did not attenuate the extent of induction of hCAR- and hPXR-regulated target genes CYP2B6 and CYP3A4 by Ginkgo biloba extract.
  
  
  CONCLUSIONS
  Ginkgo biloba extract, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are not activators of hGR. Furthermore, the extract does not influence the hGR-hCAR or the hGR-hPXR signaling pathway in primary cultures of human hepatocytes.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Aik Jiang
authors.initials: AJ
authors.lastname: Lau
authors.forename: Guixiang
authors.initials: G
authors.lastname: Yang
authors.forename: Ganesh
authors.initials: G
authors.lastname: Rajaraman
authors.forename: Christie C
authors.initials: CC
authors.lastname: Baucom
authors.forename: Thomas K H
authors.initials: TK
authors.lastname: Chang
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002478:Cells, Cultured; D000090702:Constitutive Androstane Receptor; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D020441:Ginkgo biloba; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D011987:Receptors, Steroid / Q000235:genetics
chemical_list: D000090702:Constitutive Androstane Receptor; D010936:Plant Extracts; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D010089:Oxidoreductases, N-Demethylating