title: Reproductive toxicity of Rhizoma Sparganii (Sparganium stoloniferum Buch.-Ham.) in mice: mechanisms of anti-angiogenesis and anti-estrogen pharmacologic activities.
abstract: BACKGROUND
  Indications and preliminary studies of Rhizoma Sparganii (RS) suggest its pharmacological mechanism is involved with endocrine/angiogenesis functions. We therefore studied its potential toxicity on reproduction in mice.
  
  
  METHODS
  Reproductive toxicity of 100, 200 and 400 mg/kg RS extract were studied in pregnant ICR mice and its offspring. The embryos' fibroblast growth factor-1 (FGF-1), vascular endothelial growth factor (VEGF) and estrogen receptor-α (ER-α) were evaluated as targets of endocrine/angiogenesis by immunohistochemical test.
  
  
  RESULTS
  The offspring of treated mice (100, 200 and 400 mg/kg RS extract) during their pregnancy had various pathological conditions, suggesting an abnormal FGF signaling phenomenon during pregnancy. Embryos from the 400 mg/kg group had significantly depressed levels of FGF-1 (P < 0.01) and VEGF (P < 0.05) expression levels as compared to controls by immunohistochemical test. Dysplasia in the heart (12.9%), craniofacial region (18.3%) and vertebrae (32.5%) presented in embryos of the 400 mg/kg group. Furthermore, the ER-α expression was inversely proportional to FGF-1 levels in the same embryo (P < 0.01).
  
  
  CONCLUSIONS
  These results implicate a FGF signaling abnormality in vivo and indicate that RS has anti-angiogenesis and anti-estrogen toxicity effects in pregnant rodents.
authors: Key Laboratory of Resource Biology and Biotechnology in Western China, School of Life Science, Northwest University, Xi'an 710069, China.
authors: Jie
authors: J
authors: Sun
authors: Shao
authors: S
authors: Wang
authors: Ya-Hui
authors: YH
authors: Wei
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000633:toxicity*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000302:isolation & purification / Q000633:toxicity*; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D007150:Immunohistochemistry; D019684:Magnoliopsida / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects*; D027343:Rhizome; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016220:Fibroblast Growth Factor 1