Carvacrol attenuates diabetes-associated cognitive deficits in rats

J Mol Neurosci. 2013 Nov;51(3):813-9. doi: 10.1007/s12031-013-0069-6. Epub 2013 Jul 23.

Abstract

Carvacrol (CAR), a naturally occurring phenolic monoterpene, has been demonstrated to possess various biological actions. The present study was designed to investigate the neuroprotective effect of CAR on diabetes-associated cognitive deficit (DACD) in a rat model of diabetes and exploring its potential molecular mechanism. Diabetic rats were treated with CAR by the doses of 25, 50, and 100 mg/kg for 7 weeks. Morris water maze was used for behavioral evaluation of memory. Cytoplasmic and nuclear fractions of cerebral cortex and hippocampus were prepared for the quantification of oxidative stress (MDA, SOD, and GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3. After 7 weeks of streptozotocin injection, the rats produced remarkable increase in escape latency, coupled with increased oxidative stress (increased MDA level and decreased SOD as well as reduced GSH), NF-κB p65 unit, TNF-α, IL-1β, and caspase-3 in different regions of diabetic rat brain. Interestingly, coadministration of CAR significantly and dose-dependently prevented behavioral, biochemical, and molecular changes associated with diabetes. In summary, our findings provide the first evidence that CAR can remarkably attenuate DACD and suggest the involvement of oxidative stress, inflammation, and apoptotic cascades in the development of cognitive impairment caused by diabetes. The pharmacological effect of CAR suggests that it may be used as a promising agent for the treatment of conventional antihyperglycemic regiments as well as DACD.

MeSH terms

  • Animals
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiopathology
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / etiology
  • Cymenes
  • Diabetes Mellitus, Experimental / complications*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Maze Learning
  • Monoterpenes / administration & dosage
  • Monoterpenes / therapeutic use*
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cymenes
  • Interleukin-1beta
  • Monoterpenes
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • carvacrol
  • Caspase 3