Baicalin rescues hyperglycemia-induced neural tube defects via targeting on retinoic acid signaling.

We, in this study, studied whether or not antioxidant activities of Baicalin could reduce the incidence of neural tube defects (NTDs) in the presence of hyperglycemia. Using early chick embryos, we demonstrated that Baicalin at 6 μM dramatically reduced NTDs rate and impaired neurogenesis in E4.5-day and HH10 chick embryo neural tubes induced by high glucose (HG). Likewise, immunofluorescent staining showed that Baicalin mitigated the HG-induced regression of Pax7 expression in neural tubes of both HH10 and E4.5-day chick embryos. Additionally, PHIS3 immunofluorescent staining in neural tubes of both HH10 and E4.5-day chick embryos manifested that cell proliferation inhibited by HG was significantly reversed by the administration of Baicalin, and similar result could also be observed in neurosphere assay in vitro . c-Caspase3 or γH2AX immunofluorescent staining and quantitative PCR showed that Baicalin administration alleviated HG-induced cell apoptosis and DNA damage. Bioinformatics results indicated that retinoic acid (RA) was likely to be the signaling pathway that Baicalin targeted on, and this was confirmed by whole-mount RALDH2 in situ hybridization and quantitative PCR of HH10 chick embryos in the absence/presence of Baicalin. In addition, blocking RA with an inhibitor abolished Baicalin's protective role in HG-induced NTDs, suppression of neurogenesis and cell proliferation, and induction of apoptosis, which further verified the centrality of RA in the process of Baicalin confronting HG-induced abnormal neurodevelopment.
Competing Interests: None.
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