title: Andrographolide inhibits the expression and metabolic activity of cytochrome P450 3A4 in the modified Caco-2 cells.
abstract: OBJECTIVE
  The aim of this study is to examine the effects of andrographolide on intestinal enzyme cytochrome P450 3A4 (CYP3A4) and predict whether oral administration of andrographolide-containing remedy leads to herb-drug interaction.
  
  
  METHODS
  Caco-2 cells are treated with 1α, 25-dihydroxyvitamin D3 for 3 wks to induce the expression of CYP3A4, and then andrographolide (1, 10, 100 μM) is added and treated for 72 h. Upon the further 4-h testosterone (250 μM) or nifedipine (200 μM) treatment, the basolateral medium samples and the Caco-2 monolayers are collected for analyses.
  
  
  RESULTS
  Andrographolide (1, 10, 100 μM) significantly down-regulates the mRNA level and protein level of CYP3A4, and inhibits nifedipine oxidation and testosterone 6β-hydroxylation.
  
  
  CONCLUSIONS
  Oral administration of andrographolide likely leads to reduction of the metabolic activity of intestinal CYP3A4, therefore herb preparations containing andrographolide may result to herb-drug interactions in combination therapy.
authors.affiliation: Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang, China. fengqiu2000@tom.com
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Hou
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Chen
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
mesh_terms: D000284:Administration, Oral; D018938:Caco-2 Cells; D002117:Calcitriol / Q000494:pharmacology; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D041743:Herb-Drug Interactions; D006801:Humans; D006900:Hydroxylation; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D008516:Medicine, Chinese Traditional; D009543:Nifedipine / Q000378:metabolism; D010084:Oxidation-Reduction; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism; D013997:Time Factors
chemical_list: D065692:Cytochrome P-450 CYP3A Inhibitors; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D013739:Testosterone; C030419:andrographolide; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D002117:Calcitriol; D009543:Nifedipine