title: Hyperforin inhibits cell proliferation and differentiation in mouse embryonic stem cells.
abstract: OBJECTIVE
  Hyperforin, a phloroglucinol derivative of St. John's Wort, has been identified as the major molecule responsible for this plant's products anti-depressant effects. It can be expected that exposure to St. John's Wort during pregnancy occurs with some frequency although embryotoxic or teratogenic effects of St. John's Wort and hyperforin have not yet been experimentally examined in detail. In this study, to determine any embryotoxic effects of hyperforin, we have attempted to determine whether hyperforin affects growth and survival processes of employing mouse embryonic stem (mES) cells (representing embryonic tissue) and fibroblasts (representing adult tissues).
  
  
  METHODS
  We used a modified embryonic stem cell test, which has been validated as an in vitro developmental toxicity protocol, mES cells, to assess embryotoxic potential of chemicals under investigation.
  
  
  RESULTS
  We have identified that high concentrations of hyperforin inhibited mouse ES cell population growth and induced apoptosis in fibroblasts. Under our cell culture conditions, ES cells mainly differentiated into cardiomyocytes, although various other cell types were also produced. In this condition, hyperforin affected ES cell differentiation into cardiomyocytes in a dose-dependent manner. Analysis of tissue-specific marker expression also revealed that hyperforin at high concentrations partially inhibited ES cell differentiation into mesodermal and endodermal lineages.
  
  
  CONCLUSIONS
  Hyperforin is currently used in the clinic as a safe and effective antidepressant. Our data indicate that at typical dosages it has only a low risk of embryotoxicity; ingestion of large amounts of hyperforin by pregnant women, however, may pose embryotoxic and teratogenic risks.
authors.affiliation: Department of Pharmacology, National Research Institute for Child Health and Development, Tokyo, 157-8538, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Aizawa
authors.forename: J
authors.initials: J
authors.lastname: Yamauchi
authors.forename: A
authors.initials: A
authors.lastname: Tanoue
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology*; D020902:Hypericum / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D011619:Psychotropic Drugs / Q000737:chemistry / Q000633:toxicity*; D013729:Terpenes / Q000737:chemistry / Q000633:toxicity*
chemical_list: D011619:Psychotropic Drugs; D013729:Terpenes; D010696:Phloroglucinol; C001654:hyperforin
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