title: Curcumin ameliorates high glucose-induced neural tube defects by suppressing cellular stress and apoptosis.
abstract: 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.
  
  
  METHODS
  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 μmol/L of curcumin did not significantly reduce the rate of NTDs caused by high glucose, 20 μmol/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 inositol-requiring protein-1α (p-IRE1α), phosphorylated eukaryotic initiation factor 2α (p-eIF2α), 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, People's Republic of China; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD.
authors.forename: E Albert
authors.initials: EA
authors.lastname: Reece
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD. Electronic address: pyang@upi.umaryland.edu.
authors.forename: Peixin
authors.initials: P
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000502:physiology; D002468:Cell Physiological Phenomena / Q000187:drug effects; D003474:Curcumin / Q000627:therapeutic use*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005947:Glucose / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D009436:Neural Tube Defects / Q000139:chemically induced / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D053148:Caspase 3; D003474:Curcumin; D005947:Glucose
keywords: caspase activation; curcumin; endoplasmic reticulum stress; high glucose; neural tube defects; nitrosative stress; oxidative stress