The evaluation on embryotoxicity of Dipsaci Radix with mice and embryonic stem cells

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).

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.

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).

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.