title: The evaluation on embryotoxicity of Dipsaci Radix with mice and embryonic stem cells.
abstract: BACKGROUND
  Dipsaci Radix (DR), the dried root of Dipsacus asper Wall. ex Henry, has been used to treat pregnant disorders for thousands of years, and currently has been ranked as the first selective herb for prevention of miscarriage clinically; however, there is no sufficient evidence so far to assess its safety. The purpose of this study was to examine the impacts of DR aqueous extracts on embryonic development with mice and embryonic stem cells (ESCs).
  
  
  METHODS
  In a segment II study, pregnant ICR mice were randomly assigned into 5 groups, i.e. mice were orally treated with DR aqueous extracts at dosages of 0 (distilled water, as negative controls (G1 group)), 2, 8, 32 g/kg/d (G2, G3, G4 group), and vitamin A (as positive controls (G5 group)) respectively. Maternal and embryo-fetal parameters were evaluated after cesarean section. The fetal skeletal development was further assessed with the alizarin red S and H&E staining and fluorescent imaging. Meanwhile, IC50 values for both ESCs and 3T3 cells were detected with MTT assays.
  
  
  RESULTS
  Compared to G1 group, the maternal body-weight in G3 and G4 groups was significantly lower (P<0.05-0.001), and the fetal malformation rate increased in G2, G3 and G4 groups as a dose-dependent manner, although a statistical significance was only reached in G4 group (P<0.001). The morphologic and histochemistry abnormalities of fetal skeletal development such as delayed osteogenesis and mineralization in the cartilaginous tissue were found after DR treatments (32 g/kg/d). There was no significant difference between IC50 ESC (6.826 ± 0.311 mg/ml) and IC50 3T3 (5.132 ± 0.142 mg/ml, P>0.05).
  
  
  CONCLUSIONS
  DR aqueous extracts at the dosage of 8 or 32 g/kg/d (4.3 or 17.2 folds of recommended daily-dosage for adult human respectively) might cause adverse impacts in maternal healthy and embryo-fetal development. It suggests that high-dose and long-term administration of DR preparations should be unsafe to pregnant women.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Xiao
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China. Electronic address: xumin@hkbu.edu.hk.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Guangzhou Institute of Traumatic Surgery, Guangzhou, PR China.
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: Yang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Lam
authors.initials: L
authors.lastname: Kok
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Yeuk Lung
authors.initials: YL
authors.lastname: Chow
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Zhong Zhen
authors.initials: ZZ
authors.lastname: Zhao
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Kelvin Sze-Yin
authors.initials: KS
authors.lastname: Leung
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Zhi Jun
authors.initials: ZJ
authors.lastname: Yang
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Xiao Ying
authors.initials: XY
authors.lastname: Tian
authors.affiliation: SunYat-Sen University, Guangzhou, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Meng Yun
authors.initials: MY
authors.lastname: Xin
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Baptist University Road 7, Kowloon Tong, Hong Kong, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D049917:Dipsacaceae / Q000737:chemistry*; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D053595:Embryonic Stem Cells / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005333:Fetus / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D018517:Plant Roots / Q000737:chemistry*; D011247:Pregnancy; D011897:Random Allocation
chemical_list: D010936:Plant Extracts
keywords: Dipsaci Radix; Embryonic stem cell; Embryotoxicity; Mouse; Osteogenesis