Safranal enhances non-rapid eye movement sleep in pentobarbital-treated mice

CNS Neurosci Ther. 2012 Aug;18(8):623-30. doi: 10.1111/j.1755-5949.2012.00334.x. Epub 2012 May 28.

Abstract

Aims: Safranal (2,6,6-trimethyl-1,3-cyclohexadiene-1-carboxaldehyde, C(10) H(14) O) is an active ingredient in the saffron, which is used in traditional medicine. It has been reported to have sedative and anti-epileptic effects, but its hypnotic effects remain uncertain. The aim of this study was to evaluate effects of safranal on sleep-wake cycle.

Methods: We established hypnotic-model mice treated with a low dose of pentobarbital 20 mg/kg, and administered different doses of safranal, vehicle, or diazepam. The change of sleep-wake cycle was assessed by sleep recording and c-Fos expression in the brain was analyzed by immunohistochemistry.

Results: Safranal increased the duration of non-rapid eye movement (NREM) sleep, shortened NREM sleep latency, and enhanced the delta power activity of NREM sleep. Immunohistochemical evaluation revealed that safranal increased c-Fos expression in the ventrolateral preoptic nucleus (VLPO), one of the putative sleep centers, and decreased it in the arousal histaminergic tuberomammillary nuclei (TMN).

Conclusion: These findings indicate that safranal enhances NREM sleep in pentobarbital-treated mice. The hypnotic effects of safranal may be related to the activation of the sleep-promoting neurons in the VLPO and the simultaneous inhibition of the wakefulness-promoting neurons in the TMN, suggesting that safranal may be a hypnotic substance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arousal / drug effects
  • Cyclohexenes / pharmacology*
  • Delta Rhythm / drug effects
  • Electroencephalography
  • Electromyography
  • Hypnotics and Sedatives / pharmacology*
  • Hypothalamic Area, Lateral / drug effects
  • Hypothalamic Area, Lateral / metabolism
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Pentobarbital / pharmacology*
  • Polysomnography
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Sleep / drug effects*
  • Sleep Stages / drug effects
  • Terpenes / pharmacology*

Substances

  • Cyclohexenes
  • Hypnotics and Sedatives
  • Proto-Oncogene Proteins c-fos
  • Terpenes
  • safranal
  • Pentobarbital