Quercetin protects rat dorsal root ganglion neurons against high glucose-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition

Acta Pharmacol Sin. 2013 Sep;34(9):1140-8. doi: 10.1038/aps.2013.59. Epub 2013 Jun 17.

Abstract

Aim: To examine the effects of quercetin, a natural antioxidant, on high glucose (HG)-induced apoptosis of cultured dorsal root ganglion (DRG) neurons of rats.

Methods: DRG neurons exposed to HG (45 mmol/L) for 24 h were employed as an in vitro model of diabetic neuropathy. Cell viability, reactive oxygen species (ROS) level and apoptosis were determined. The expression of NF-кB, IкBα, phosphorylated IкBα and Nrf2 was examined using RT PCR and Western blot assay. The expression of hemeoxygenase-1 (HO-1), IL-6, TNF-α, iNOS, COX-2, and caspase-3 were also examined.

Results: HG treatment markedly increased DRG neuron apoptosis via increasing intracellular ROS level and activating the NF-κB signaling pathway. Co-treatment with quercetin (2.5, 5, and 10 mmol/L) dose-dependently decreased HG-induced caspase-3 activation and apoptosis. Quercetin could directly scavenge ROS and significantly increased the expression of Nrf-2 and HO-1 in DRG neurons. Quercetin also dose-dependently inhibited the NF-κB signaling pathway and suppressed the expression of iNOS, COX-2, and proinflammatory cytokines IL-6 and TNF-α.

Conclusion: Quercetin protects rat DRG neurons against HG-induced injury in vitro through Nrf-2/HO-1 activation and NF-κB inhibition, thus may be beneficial for the treatment of diabetic neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Glucose / toxicity*
  • Heme Oxygenase (Decyclizing) / biosynthesis*
  • NF-E2-Related Factor 2 / biosynthesis*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology
  • Pregnancy
  • Quercetin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • NF-E2-Related Factor 2
  • NF-kappa B
  • Neuroprotective Agents
  • Nfe2l2 protein, rat
  • Reactive Oxygen Species
  • Quercetin
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Glucose