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.

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.

Protective effects of fractions from Pseudostellaria heterophylla against cobalt chloride-induced hypoxic injury in H9c2 cell.

ETHNOPHARMACOLOGICAL RELEVANCE: Except for as a well-known tonic Chinese herbal medicine for the treatment of splenic asthenia, anorexia, lassitude and weakness, the roots of Pseudostellaria heterophylla was also used in Chinese medicines for the treatment of palpitation. AIM OF THE STUDY: The study was designed to determine whether fractions from Pseudostellaria heterophylla could provide cardioprotection on hypoxic cardiomyocytes, what structural types of compounds were responsible for the observed effects, and which is the possible mechanism of action. MATERIALS AND METHODS: The roots of Pseudostellaria heterophylla were extracted successively with 70% aqueous ethanol and water to give a 70% ethanol extract and a water extract. The latter was first precipitated by 80% ethanol and then protein-removed by the Sevag method to give a fraction enriched in polysaccarides (PHP). The former was separated by column chromatography into a fraction enriched in small-molecule sugars and amino acids (PHSSAC), saponins (PHS), cyclopeptides (PHCP), and sapogenins (PHSG). UV spectral or chemical methods were used to confirm the five fractions. The cardioprotective effects of the fractions were evaluated by measuring the viability and the leakage of lactate dehydrogenase (LDH) of the fraction-pretreated cardiomyocyte H9c2 after exposure to CoCl2-induced hypoxia. The mechanism of action was studied by investigating the nature of cell death inhibition (by Annexin V/PI flow cytometric analysis) and their effects on the levels of malonaldehyde (MDA), superoxide dismutase (SOD) and intracellular reactive oxygen species (ROS). RESULTS: Fractions PHS and PHP could attenuate CoCl2-induced hypoxic damage to an extent higher than or comparable to the effect of the positive control N-acetyl-l-cysteine (NAC). Pretreatment of the cells with 800 µg/mL of PHS or 10mg/mL of PHP markedly decreased the level of MDA, reduced intracellular ROS, increased the activity of SOD, and reduced leakage of LDH to the levels close to or better than that with 326 µg/mL of NAC. Reduction of apoptosis was also observed for both fractions. CONCLUSIONS: The overall results suggested that the traditional use of this plant for the treatment of palpitation may be attributed to the presence of cardioprotective agents in Pseudostellaria heterophylla. PHP and PHS were the two active fractions responsible for its cardioprotective effect. The mechanism might involve protections of the cell membrane from hypoxic damage and of the cells from oxidative injury via preventing increased oxidative stress. Protection of the cells via inhibition of cellular apoptosis may also be involved.

Protective effect of oxymatrine on myocardial fibrosis induced by acute myocardial infarction in rats involved in TGF-ß1-Smads signal pathway.

Oxymatrine (1), a component extracted from a traditional Chinese herb Sophora japonica (Sophora flavescens Ait.), has been demonstrated to have a variety of pharmacological actions. Abundant experimental evidence indicates that 1 may exert a protective effect on the cardiovascular system. This study was designed to explore the possible role of 1 against myocardial fibrosis induced by acute myocardial infarction (AMI) and its modulation on transforming growth factor beta 1 (TGF-ß(1))-Smads signaling pathways. Rats with AMI induced by ligation of left anterior descending branch were randomly assigned to receive 1 50 and 25 mg/kg intragastrically, and model group which were further compared with sham-operated group, and positive group treated with captopril. The effects of 4-week therapy with 1 starting 24 h after infarction had been investigated based on (1) hemodynamics, (2) tissue weights, (3) biochemical indicator (hydroxyproline contents in left ventricle), and (4) TGF-ß(1), TGF-ß(1) receptor (TßR(1)), Smad3, Smad4, Smad7, Col1, and Col3 expression by semi-quantitative reverse transcription PCR. Treatment with 1 significantly ameliorated hemodynamics, inhibited the expression of TßR(1) mRNA and Smad3 mRNA, and reduced the left ventricle weight/body weight. The results of this research indicated that 1 might protect against myocardial fibrosis and the mechanism may be involved in modulating TGF-ß(1)-Smads signal pathway.