title: Identification of novel pregnane X receptor activators from traditional Chinese medicines.
abstract: OBJECTIVE
  To investigate the ability of traditional Chinese medicines (TCMs) and their bioactive compounds to activate pregnane X receptor (PXR) signalling pathway.
  
  
  METHODS
  We screened ethanol extracts of 28 commonly used TCMs for their capability to induce cytochrome P450 3A4 (CYP3A4) via PXR signalling pathway using a cell-based reporter gene assay combined with RT-PCR analysis. In addition, 34 bioactive components from these TCMs were examined for their potential to activate PXR.
  
  
  RESULTS
  Our observations showed that 22 ethanol extracts and 8 compounds could activate human PXR and induce CYP3A4 reporter construct in HepG2 cells. Among them, Ginkgo biloba, Ligusticum chuanxiong, Chinese angelica, prepared Rehmannia root, Epimedium brevicornum, Atractylodes macrocephala, Schisandra chinensis, Paeonia lactiflora, Ophiopogon japonicus, Polygonum multiflorum, Coptis chinensis, Artemisia scoparia, Trichosanthes kirilowii, Silybum marianum, Gardenia fruit and Lycium chinense could strongly trans-activate PXR. Moreover, ligustilide, schisantherin A, berberine hydrochloride and trans-resveratrol were identified for the first time as efficacious PXR agonists.
  
  
  CONCLUSIONS
  Twenty-two TCM ethanol extracts and eight bioactive compounds could activate PXR signalling pathway and induce CYP3A4 reporter gene. Therefore, caution should be taken when these PXR activators are used in combination with prescribed drugs metabolized by CYP3A4.
authors.affiliation: Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Chunna
authors.initials: C
authors.lastname: Yu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chai
authors.forename: Lushan
authors.initials: L
authors.lastname: Yu
authors.forename: Shuqing
authors.initials: S
authors.lastname: Chen
authors.forename: Su
authors.initials: S
authors.lastname: Zeng
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology; D034242:Cyclooctanes / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D017930:Genes, Reporter; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D019684:Magnoliopsida / Q000737:chemistry*; D008516:Medicine, Chinese Traditional; D010946:Plants, Medicinal / Q000737:chemistry; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000378:metabolism*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D034242:Cyclooctanes; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D017705:Lignans; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D013267:Stilbenes; D001599:Berberine; C027820:ligustilide; C034557:schizandrer A; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D015107:4-Butyrolactone; D000077185:Resveratrol