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


CONCLUSIONS
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.
State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.
Zheng
Z
Liu
Xin-Hong
XH
Xu
Tian-Ya
TY
Liu
Zong-Yuan
ZY
Hong
Yoshihiro
Y
Urade
Zhi-Li
ZL
Huang
Wei-Min
WM
Qu
D000818:Animals; D001143:Arousal / Q000187:drug effects; D053138:Cyclohexenes / Q000494:pharmacology*; D003700:Delta Rhythm / Q000187:drug effects; D004569:Electroencephalography; D004576:Electromyography; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010424:Pentobarbital / Q000494:pharmacology*; D017286:Polysomnography; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects; D013729:Terpenes / Q000494:pharmacology*
D053138:Cyclohexenes; D006993:Hypnotics and Sedatives; D016760:Proto-Oncogene Proteins c-fos; D013729:Terpenes; C087963:safranal; D010424:Pentobarbital