Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system.
Semen Zizhiphi Spinozae has been used extensively for the treatment of insomnia. This study investigated the effect and possible mechanism of action of spinosin (also known as 2''-beta-o-glucopyranosyl swertisin), a major constituent of semen Zizhiphi Spinozae, on sleep in mice. The present results showed that spinosin significantly and dose-dependently augmented pentobarbital (45 mg/kg, i.p.)-induced sleep, reflected by increased sleep time and reduced sleep latency assessed with the loss-of-righting reflex, and these effects were potentiated by the 5-hydroxytryptamine (serotonin) precursor 5-hydroxytryptophan (5-HTP, 2.5 mg/kg,i.p.). With a subhypnotic dose of pentobarbital (28 mg/kg, i.p.), spinosin significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleep time, and spinosin significantly reversed this effect. The dopamine precursor L-3-(3, 4-dihydroxyphenylalanine (L-DOPA) reduced pentobarbital-induced sleep, an effect not significantly affected by spinosin. These results suggest that spinosin potentiated pentobarbital-induced sleep via a serotonergic mechanism.
Wang
Li-En
LE
Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100083, China.
Bai
Yan-Jing
YJ
Shi
Xiao-Rong
XR
Cui
Xiang-Yu
XY
Cui
Su-Ying
SY
Zhang
Fan
F
Zhang
Qing-Ying
QY
Zhao
Yu-Ying
YY
Zhang
Yong-He
YH
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D010134:Fenclonine / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010424:Pentobarbital / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D012890:Sleep / Q000187:drug effects*; D031957:Ziziphus / Q000737:chemistry*
D015259:Dopamine Agents; D005419:Flavonoids; D006993:Hypnotics and Sedatives; D018490:Serotonin Agents; D012701:Serotonin; D007980:Levodopa; C055669:spinosin; D006916:5-Hydroxytryptophan; D010424:Pentobarbital; D010134:Fenclonine