title: Spinosin, a C-glycoside flavonoid from semen Zizhiphi Spinozae, potentiated pentobarbital-induced sleep via the serotonergic system.
abstract: 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.
authors.affiliation: Department of Pharmacology, Peking University, School of Basic Medical Science, 38 Xueyuan Lu, Beijing 100083, China.
authors.forename: Li-En
authors.initials: LE
authors.lastname: Wang
authors.forename: Yan-Jing
authors.initials: YJ
authors.lastname: Bai
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Shi
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Cui
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Cui
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Qing-Ying
authors.initials: QY
authors.lastname: Zhang
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Zhao
authors.forename: Yong-He
authors.initials: YH
authors.lastname: Zhang
mesh_terms: 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*
chemical_list: 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