Effect of maternal exposure to Curcumae Rhizoma during pregnancy on neurodevelopment and apoptosis mechanism in offspring.
10.19540/j.cnki.cjcmm.20181012.004
- Author:
Xiao-Ming LI
1
;
Hua RONG
1
;
Jia-Yi QIAN
1
;
Miao-Xian DONG
1
;
Ying-Cai NIU
1
Author Information
1. Institute of Medicine, Qiqihar Medical College Qiqihar 161006, China.
- Publication Type:Journal Article
- Keywords:
Curcumae Rhizoma;
Nrf2 knockout mice;
developmental neurotoxicity;
syndrome of blood stasis
- MeSH:
Animals;
Apoptosis;
Brain;
drug effects;
Caspases;
genetics;
Curcuma;
chemistry;
Drugs, Chinese Herbal;
pharmacology;
Female;
Maternal Exposure;
Mice;
Mice, Inbred C57BL;
Mice, Knockout;
NF-E2-Related Factor 2;
genetics;
Pregnancy;
Proto-Oncogene Proteins c-bcl-2;
genetics;
Random Allocation;
Rhizome;
chemistry;
Signal Transduction
- From:
China Journal of Chinese Materia Medica
2019;44(3):541-545
- CountryChina
- Language:Chinese
-
Abstract:
Curcumae Rhizoma is a Chinese medicinal herb that is contraindicated during pregnancy. Cold-congelation and blood-stasis are corresponding syndromes to Curcumae Rhizoma. Whether syndrome-based treatment is associated with developmental neurotoxicity of Curcumae Rhizoma remains to be unclear. To verify the theory of traditional Chinese medicine of "syndrome-based treatment during pregnancy", the present study induced the mice blood stasis model by immersing mice in ice water. Pregnant C57 BL/6 wild type(WT) mice and pregnant Nrf2 knock out(KO) mice were randomly divided into control groups and Rhizoma Curcumae exposure groups. The mice were exposed to Rhizoma Curcumae during day 5 to day 18 after pregnancy. The neurodevelopment was examined to evaluate the differences of developmental neurotoxicity between normal and blood-stasis pregnant mice exposed to Rhizoma Curcumae. caspase-3 and caspase-9 activity in brain of the offspring were measured by colorimetric assays. Bcl-2 mRNA and protein expression in brain of the offspring were examined by Real-time RT-PCR and Western blot, respectively. According to the findings, C57 BL/6 mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) had a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring, compared with the normal control group, but with no significant change in those of blood-stasis pregnant mice offspring. However, mice exposed to Rhizoma Curcumae(10.0 g·kg~(-1)) showed no change in Bcl-2 gene expression and p38 MAPK phosphorylation in brain of the offspring. Nrf2 gene knockout using CRISPR/Cas9 resulted in a longer positive occurring time of the surface righting reflex test of offspring and higher caspase-3 and caspase-9 activities in brain of offspring. In conclusion, developmental neurotoxicity of the blood-stasis pregnant mice exposed to Rhizoma Curcumae was weaker than that of the normal pregnant mice. Nrf2 activation involved in the phenomenon of Rhizoma Curcumae of "syndrome-based treatment during pregnancy", but the upstream signal pathway mechanism value shall be further investigated.