Anti-oxidative and anti-inflammatory effects of cinnamaldehyde on protecting high glucose-induced damage in cultured dorsal root ganglion neurons of rats.
- Author:
Dan YANG
1
;
Xiao-Chun LIANG
2
;
Yue SHI
1
;
Qing SUN
1
;
Di LIU
1
;
Wei LIU
1
;
Hong ZHANG
3
Author Information
- Publication Type:Journal Article
- Keywords: cinnamaldehyde; dorsal root ganglion; high glucose; nuclear factor erythroid 2-related factor 2; nuclear factor-kappa B
- MeSH: Acrolein; administration & dosage; analogs & derivatives; pharmacology; Animals; Anti-Inflammatory Agents; pharmacology; Apoptosis; drug effects; Blotting, Western; Caspase 3; metabolism; Cell Survival; drug effects; Cells, Cultured; Ganglia, Spinal; drug effects; metabolism; pathology; Glucose; toxicity; Heme Oxygenase (Decyclizing); metabolism; I-kappa B Proteins; metabolism; Interleukin-6; metabolism; NF-E2-Related Factor 2; metabolism; NF-kappa B; metabolism; Neurons; drug effects; metabolism; pathology; Neuroprotective Agents; pharmacology; Oxidation-Reduction; drug effects; Phosphorylation; drug effects; Rats, Sprague-Dawley; Reactive Oxygen Species; metabolism; Tumor Necrosis Factor-alpha; metabolism
- From: Chinese journal of integrative medicine 2016;22(1):19-27
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo 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.
METHODSHG-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.
RESULTSCinnamaldehyde 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.
CONCLUSIONSCinnamaldehyde 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.
