Potentiating effect of spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, on pentobarbital-induced sleep may be related to postsynaptic 5-HT(1A) receptors

Phytomedicine. 2010 May;17(6):404-9. doi: 10.1016/j.phymed.2010.01.014. Epub 2010 Feb 20.


Previous results have suggested that spinosin, a C-glycoside flavonoid of Semen Ziziphi spinosae, potentiates pentobarbital-induced sleep via the serotonergic system. The present study investigated whether spinosin potentiates pentobarbital-induced sleep via serotonin-1A (5-hydroxytryptamine, 5-HT(1A)) receptors. The results demonstrated that spinosin significantly augmented pentobarbital (35 mg/kg, i.p.)-induced sleep in rats, reflected by reduced sleep latency and increased total sleep time, non-rapid eye movement (NREM) sleep time, and REM sleep time. With regard to NREM sleep duration, spinosin mainly increased slow-wave sleep (SWS). Additionally, spinosin (15mg/kg, i.g.) significantly antagonized 5-HT(1A) agonist 8-OH-DPAT (0.1mg/kg, i.p.)-induced reductions in total sleep time, NREM sleep, REM sleep, and SWS in pentobarbital-treated rats. These results suggest that spinosin may be an antagonist at postsynaptic 5-HT(1A) receptors because these effects of 8-OH-DPAT were considered to be mediated via postsynaptic 5-HT(1A) receptors. Moreover, co-administration of spinosin and the 5-HT(1A) antagonist 4-iodo-N-{2-[4-(methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylbenzamide (p-MPPI), at doses that are ineffective when administered alone (spinosin 5mg/kg, p-MPPI 1mg/kg), had significant augmentative effects on pentobarbital-induced sleep, reflected by reduced sleep latency and increased total sleep time, NREM sleep, and REM sleep. In contrast to the attenuating effects of p-MPPI on REM sleep via presynaptic 5-HT(1A) autoreceptors, 15mg/kg spinosin significantly increased REM sleep. These results suggest that the effect of spinosin on REM sleep in pentobarbital-treated rats may be related to postsynaptic 5-HT(1A) receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors
  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use
  • Animals
  • Drug Synergism
  • Drug Therapy, Combination
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Glycosides
  • Male
  • Monosaccharides
  • Pentobarbital / pharmacology
  • Phytotherapy
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Seeds
  • Serotonin / metabolism
  • Serotonin 5-HT1 Receptor Antagonists*
  • Sleep / drug effects*
  • Sleep Initiation and Maintenance Disorders / drug therapy
  • Sleep, REM
  • Time Factors
  • Wakefulness / drug effects*
  • Ziziphus / chemistry*


  • Aminopyridines
  • C-glycoside
  • Drugs, Chinese Herbal
  • Flavonoids
  • Glycosides
  • Monosaccharides
  • Piperazines
  • Serotonin 5-HT1 Receptor Antagonists
  • 4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine
  • Serotonin
  • spinosin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Pentobarbital