Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis

OBJECTIVE: Curcumin is a naturally occurring polyphenol present in the roots of the Curcuma longa plant (turmeric), which possesses antioxidant, antitumorigenic, and antiinflammatory properties. Here, we test whether curcumin treatment reduces high glucose-induced neural tube defects (NTDs), and if this occurs via blocking cellular stress and caspase activation. STUDY DESIGN: Embryonic day 8.5 mouse embryos were collected for use in whole-embryo culture under normal (100 mg/dL) or high (300 mg/dL) glucose conditions, with or without curcumin treatment. After 24 hours in culture, protein levels of oxidative stress makers, nitrosative stress makers, endoplasmic reticulum (ER) stress makers, cleaved caspase 3 and 8, and the level of lipid peroxides were determined in the embryos. After 36 hours in culture, embryos were examined for evidence of NTD formation. RESULTS: Although 10 mu mol/L of curcumin did not significantly reduce the rate of NTDs caused by high glucose, 20 mu mol/L of curcumin significantly ameliorated high glucose-induced NTD formation. Curcumin suppressed oxidative stress in embryos cultured under high glucose conditions. Treatment reduced the levels of the lipid peroxidation marker, 4-hydroxynonenal, nitrotyrosine-modified protein, and lipid peroxides. Curcumin also blocked ER stress by inhibiting phosphorylated protein kinase RNA-like ER kinase, phosphorylated inositolrequiring protein-1 alpha (p-IRE1 alpha), phosphorylated eukaryotic initiation factor 2 alpha (p-eIF2 alpha), C/EBP-homologous protein, binding immunoglobulin protein, and x-box binding protein 1 messenger RNA splicing. Additionally, curcumin abolished caspase 3 and caspase 8 cleavage in embryos cultured under high glucose conditions. CONCLUSION: Curcumin reduces high glucose-induced NTD formation by blocking cellular stress and caspase activation, suggesting that curcumin supplements could reduce the negative effects of diabetes on the embryo. Further investigation will be needed to determine if the experimental findings can translate into clinical settings.