title: Anti-oxidative and anti-inflammatory effects of cinnamaldehyde on protecting high glucose-induced damage in cultured dorsal root ganglion neurons of rats.
abstract: OBJECTIVE
  To examine the mechanism underlying the beneficial role of cinnamaldehyde on oxidative damage and apoptosis in high glucose (HG)-induced dorsal root ganglion (DRG) neurons in vitro.
  
  
  METHODS
  HG-treated DRG neurons were developed as an in vitro model of diabetic neuropathy. The neurons were randomly divided into five groups: the control group, the HG group and the HG groups treated with 25, 50 and 100 nmol/L cinnamaldehyde, respectively. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and apoptosis rate was evaluated by the in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. The intracellular level of reactive oxygen species (ROS) was measured with flow cytometry. Expression of nuclear factor-kappa B (NF-κB), inhibitor of κB (IκB), phosphorylated IκB (p-IκB), tumor necrosis factor (TNF)-α, interleukin-6 (IL-6) and caspase-3 were determined by western blotting and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were also measured by western blotting.
  
  
  RESULTS
  Cinnamaldehyde reduced HG-induced loss of viability, apoptosis and intracellular generation of ROS in the DRG neurons via inhibiting NF-κB activity. The western blot assay results showed that the HG-induced elevated expressions of NF-κB, IκB and p-IκB were remarkably reduced by cinnamaldehyde treatment in a dose-dependent manner (P <0.01). The HG-induced over-expression of NF-κB p65 mRNA was remarkably attenuated after cinnamaldehyde treatment in a dose-dependent manner (P <0.01). However, the expressions of Nrf2 and HO-1 were not upregulated. Treatment with cinnamaldehyde not only attenuated caspase-3 activation and the caspase cleavage cascade in DRG neurons, but also lowered the elevated IL-6, TNF-α, cyclo-oxygenase and inducible nitric oxide synthase levels, indicating a reduction in inflammatory damage.
  
  
  CONCLUSIONS
  Cinnamaldehyde protected DRG neurons from the deleterious effects of HG through inactivation of NF-κB pathway but not through activation of Nrf2/HO-1. And thus cinnamaldehyde may have potential application as a treatment for DPN.
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Translational Medicine Center, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Translational Medicine Center, Chinese Academy of Medical Sciences, Beijing, 100730, China. xcliang@vip.sina.com.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Liang
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Translational Medicine Center, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Translational Medicine Center, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Translational Medicine Center, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Translational Medicine Center, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Cell Resource Center, Institute of Basic Medical Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000633:toxicity*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000171:Acrolein; D006419:Heme Oxygenase (Decyclizing); D053148:Caspase 3; D005947:Glucose; C012843:cinnamaldehyde
keywords: cinnamaldehyde; dorsal root ganglion; high glucose; nuclear factor erythroid 2-related factor 2; nuclear factor-kappa B