The Potential Impact of Radix Paeoniae Alba in Embryonic Development of Mice.

Although Radix Paeoniae Alba (RPA) has been ranked as one of the top 6 herbs used frequently to prevent and treat miscarriages clinically, there is no clear evidence regarding its safety in embryonic development. This study aims to evaluate the potential impacts of RPA on embryonic stem cells (ESCs) and pregnant mice. Cytotoxicity assays of the extract were performed in ESCs and 3T3 cells. Pregnant ICR mice were orally treated with RPA extracts at dosages of 0 (G1 group as negative controls), 2, 8 and 32 g/kg/day (G2, G3 and G4 groups) respectively from the gestation day (Gd) 6-15. On Gd 18, there was no significant difference in the IC50 values between ESCs and 3T3 cells (p > 0.05). There was no significant difference in the maternal and fetal evaluations among four groups (p > 0.05). Fetal IL-2, IL-2r, TNF-α, TNF-αr, IL-4, IL-4r, IL-10r, IL-17 and IL-17r of G4 group were significantly lower than G1 group (p < 0.05). In conclusion, RPA at dosage of 32 g/kg/day (16-folds of human daily dosage) did not cause adverse impact in cultured ESCs and pregnant mice. RPA might down-regulate fetal Th1/Th2/Th17 cytokines and receptors maybe beneficial to embryonic survival and development. Copyright © 2017 John Wiley & Sons, Ltd.

[In vivo study of Chuankezhi metabolism in rat].

To study the metabolic products of main compounds of Chuankezhi injection in rat, 12 Sprague Dawley rats were classed into 2 groups, a blank control group and an intermuscular administration group, respectively. Rat feces and urine samples were collected from 0−24 h and 24−48 h after administration. All the samples were ultrasonically treated with methanol and then analyzed using LC-LTQ Orbitrap MSn. By comparison with the total ion chromatogram of samples from the blank control group, the metabolites in the samples of drug-treated group were screened. These metabolites were further analyzed by multistage product ion scanning and comparison of retention time with reference substances. As a result, a total of 12 flavonoid metabolites were tentatively identified from the rat feces and no metabolite was discovered in the rat urine. Epimedin C and icariin were detected in the rat blood samples after 30 min of administration, but their metabolites and other original flavones were not detected. Furthermore, no original flavones and their metabolites were detected in rat blood samples after 2 and 4 h of administration. The potential metabolism paths were further characterized and the principal in vivo transformation of flavones from Chuankezhi injection were deglycosylation, dehydration, methylation, oxidation and isomerization in rats.

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

ETHNOPHARMACOLOGICAL RELEVANCE: 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). MATERIAL AND METHOD: 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. RESULT: 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). CONCLUSION: 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.

Effects of curcumin in treatment of experimental pulmonary fibrosis: a comparison with hydrocortisone.

To compare curcumin with hydrocortisone for treating bleomycin-induced pulmonary fibrosis (BLMPF), four groups of rats were injected with 1.5 mg/kg bleomycin intratracheally. Then the Group HC rats were treated with three injections of 2mg/kg hydrocortisone i.p.; Group CH and CL rats, respectively, were orally given 500 or 250 mg/kg curcumin daily; and Group PC rats were given deionized water alone. After 28 days of treatment, lung samples were examined by H-E staining, Masson's staining and immunohistochemical analyses and pulmonary type I collagen (Col-I), inducible nitric oxide synthetase (iNOS) and transforming growth factor-beta1 (TGF-beta1) were determined by Western blotting and real-time RT PCR analyses. The results showed that (1) Group PC rats had histopathological characteristics of BLMPF with significant increase in their protein/mRNA expressions of Col-I (+114%/+173%), iNOS (+146%/+523%) and TGF-beta1 (+476%/+527%) (P<0.01); (2) in Group HC, CH and CL rats, protein/mRNA expressions of Col-I (-39%/-52%, -31%/-57%, -33%/-58%), iNOS (-31%/-51%, -31%/-79%, -31%/-47%) and TGF-beta1 (-64%/-78%, -75%/-74%, -81%/-79%) were significantly lower than Group PC (P<0.05); (3) except for levels of TGF-beta1 protein, there was no significant difference among Group CH, CL and HC rats (P>0.05). It suggests that curcumin may play a similar role as hydrocortisone in preventing BLMPF.