title: Pharmacological mechanisms of black cohosh in Sprague-Dawley rats.
abstract: BACKGROUND
  Studies indicate that extracts and purified components from black cohosh inhibit the growth of human breast cancer cells, but the molecular targets and signaling pathways have not yet been defined.
  
  
  OBJECTIVE
  This study examines the pharmacological mechanisms and toxicological effects in the short term of the herb black cohosh on female Sprague-Dawley rats.
  
  
  METHODS
  To assess effects on gene activity and lipid content, we treated female Sprague-Dawley rats with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 or 0mg/kg. Four animals for each group were sacrificed at 1, 6 and 24h after treatment; liver tissue and serum samples were obtained for gene expression and lipid analysis.
  
  
  RESULTS
  Microarray analysis of rat liver tissue indicated that black cohosh markedly downregulated mitochondrial oxidative phosphorylation genes. Phospholipid biosynthesis and remodeling, PI3-Kinase and sphingosine signaling were upregulated, driven largely by an upregulation of several isoforms of phospholipase C. Hierarchical clustering indicated that black cohosh clustered with antiproliferative compounds, specifically tubulin binding vinca alkaloids and DNA alkylators. In support of this, black cohosh repressed the expression of cyclin D1 and ID3, and inhibited the proliferation of HepG2, p53 positive, liver cancer cells. Black cohosh reduced the level of free fatty acids at 6 and 24h and triglycerides at 6h in the serum, but increased the free fatty acid and triglyceride content of the treated livers at 24h.
  
  
  CONCLUSIONS
  Our results suggest that black cohosh warrants further study for breast cancer prevention and therapy.
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. lseinbond@gmail.com
authors.forename: Linda Saxe
authors.initials: LS
authors.lastname: Einbond
authors.forename: Morando
authors.initials: M
authors.lastname: Soffritti
authors.forename: Davide Degli
authors.initials: DD
authors.lastname: Esposti
authors.forename: Hsan-Au
authors.initials: HA
authors.lastname: Wu
authors.forename: Eva
authors.initials: E
authors.lastname: Tibaldi
authors.forename: Michelina
authors.initials: M
authors.lastname: Lauriola
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.forename: Taesik
authors.initials: T
authors.lastname: Park
authors.forename: Tao
authors.initials: T
authors.lastname: Su
authors.forename: Lesley
authors.initials: L
authors.lastname: Huggins
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Marc
authors.initials: M
authors.lastname: Roller
authors.forename: Richard
authors.initials: R
authors.lastname: Brennan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D031885:Cimicifuga / Q000737:chemistry*; D056741:Cyclin D / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006027:Glycosides / Q000494:pharmacology / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013110:Sphingosine / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014404:Tubulin / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D015854:Up-Regulation; D031053:Vinca / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D056741:Cyclin D; D005227:Fatty Acids; D006027:Glycosides; D010936:Plant Extracts; D014280:Triglycerides; D014315:Triterpenes; D014404:Tubulin; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D010738:Type C Phospholipases; D013110:Sphingosine